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Yale BIDS Xu Lab 38

JAMA_FINAL102

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 3-month-old boy was referred for evaluation of multiple cutaneous red papules. The guardian reported first noticing the papules at birth. During the following months, the papules grew in number and size, involving the head and neck, trunk, extremities, right palm, mons pubis, and buttocks. At the height of severity, the patient had 39 lesions, some of which were associated with ulceration and bleeding. The patient was born at full term via spontaneous vaginal delivery; the birth mother had not received prenatal care. Neither the birth mother nor the infant had any known history of environmental or occupational exposure to hazardous substances. The paternal family medical history was unremarkable; maternal family medical history was unknown. Physical examination revealed numerous bright red macules, papules, and plaques ranging in size from 1.0 × 1.0 mm to 2.2 × 2.3 cm, many of which had hemorrhagic crust and dark scale (Figure, A and B). Additional examination findings included retrognathia, thickened maxillary frenulum, and anterior ankyloglossia. ### OUTPUT:

Congenital disseminated pyogenic granuloma

['Pediatrics', 'Dermatology', 'Neonatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 3-month-old girl was referred for evaluation of multiple cutaneous red papules. The guardian reported first noticing the papules at birth. During the following months, the papules grew in number and size, involving the head and neck, trunk, extremities, right palm, mons pubis, and buttocks. At the height of severity, the patient had 39 lesions, some of which were associated with ulceration and bleeding. The patient was born at full term via spontaneous vaginal delivery; the birth mother had not received prenatal care. Neither the birth mother nor the infant had any known history of environmental or occupational exposure to hazardous substances. The paternal family medical history was unremarkable; maternal family medical history was unknown. Physical examination revealed numerous bright red macules, papules, and plaques ranging in size from 1.0 × 1.0 mm to 2.2 × 2.3 cm, many of which had hemorrhagic crust and dark scale (Figure, A and B). Additional examination findings included retrognathia, thickened maxillary frenulum, and anterior ankyloglossia. ### OUTPUT:

JAMA_FINAL103

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 28-year-old White woman with no remarkable medical history presented with difficulty phonating and singing for the past 15 months. She also reported odynophonia, globus sensation, and mild dysphagia to solids. The patient had been treated previously with steroids and amoxicillin for the presumptive diagnosis of chronic laryngitis but reported no improvement in symptoms. Laboratory workup was positive for elevated antinuclear antibodies and erythrocyte sedimentation rate and was consequently referred to our institution. On presentation, the patient had only minimal dysphonia. She underwent a transnasal flexible laryngoscopy that demonstrated a severely edematous epiglottis, posterior pharyngeal wall, aryepiglottic folds, and arytenoids (Figure, A). The vocal folds were difficult to visualize but seemed normal in appearance and mobility. Stroboscopy could not be performed because of obstruction from the prolapsing arytenoids. Interestingly, the patient denied any shortness of breath. Results of laboratory testing revealed normal levels of all components of a comprehensive metabolic panel, thyroid-stimulating hormone, and angiotensin-converting enzyme. The patient’s erythrocyte sedimentation rate was elevated to 75 mm/h (reference range, 0-15 mm/h). Findings of chest radiography were normal. An esophagram showed no evidence of reflux esophagitis and a computed tomography of the neck showed edema of the supraglottis with some edema in the posterior hypopharyngeal wall. ### OUTPUT:

Laryngeal sarcoidosis

['Laryngology', 'Otolaryngology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 28-year-old White man with no remarkable medical history presented with difficulty phonating and singing for the past 15 months. He also reported odynophonia, globus sensation, and mild dysphagia to solids. The patient had been treated previously with steroids and amoxicillin for the presumptive diagnosis of chronic laryngitis but reported no improvement in symptoms. Laboratory workup was positive for elevated antinuclear antibodies and erythrocyte sedimentation rate and was consequently referred to our institution. On presentation, the patient had only minimal dysphonia. He underwent a transnasal flexible laryngoscopy that demonstrated a severely edematous epiglottis, posterior pharyngeal wall, aryepiglottic folds, and arytenoids (Figure, A). The vocal folds were difficult to visualize but seemed normal in appearance and mobility. Stroboscopy could not be performed because of obstruction from the prolapsing arytenoids. Interestingly, the patient denied any shortness of breath. Results of laboratory testing revealed normal levels of all components of a comprehensive metabolic panel, thyroid-stimulating hormone, and angiotensin-converting enzyme. The patient’s erythrocyte sedimentation rate was elevated to 75 mm/h (reference range, 0-15 mm/h). Findings of chest radiography were normal. An esophagram showed no evidence of reflux esophagitis and a computed tomography of the neck showed edema of the supraglottis with some edema in the posterior hypopharyngeal wall. ### OUTPUT:

JAMA_FINAL104

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 72-year-old homeless man was referred for management of a recurrent cutaneous squamous cell carcinoma (SCC) of the right temple and brow. On review of history, maxillofacial magnetic resonance imaging (MRI) with and without contrast done 5 months prior to presentation showed a 5.9 × 5.3 × 3.7-cm mass centered at the right temple that tracked along the right lateral orbital wall as well as an enhancing right intraparotid lymph node. The patient was lost to follow-up and re-presented 5 months later with an enlarged crusting and ulcerating lesion of the right temple/brow (Figure 1A). On ocular examination, best-corrected visual acuity was 20/100 OD and 20/125 OS due to cataracts, pupils reacted normally without afferent pupillary defect, and ocular motility was full. He had mild proptosis in the right eye and right lower eyelid retraction. Orbicularis strength was intact and symmetric in both eyes. MRI of the orbits, face, and neck with and without contrast showed a 6.1 × 5.7 × 4.0-cm mass with erosion through the right sphenoid wing, involvement of the lacrimal gland, and abutment of the lateral rectus (Figure 1B). In discussing treatment strategies for the orbital component of the disease, the patient was strongly against an orbital exenteration. ### OUTPUT:

Stage T3N1M0 recurrent cutaneous SCC of the face

['Dermatology', 'Facial Plastic Surgery', 'Head and Neck Cancer', 'Oncology', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 72-year-old homeless woman was referred for management of a recurrent cutaneous squamous cell carcinoma (SCC) of the right temple and brow. On review of history, maxillofacial magnetic resonance imaging (MRI) with and without contrast done 5 months prior to presentation showed a 5.9 × 5.3 × 3.7-cm mass centered at the right temple that tracked along the right lateral orbital wall as well as an enhancing right intraparotid lymph node. The patient was lost to follow-up and re-presented 5 months later with an enlarged crusting and ulcerating lesion of the right temple/brow (Figure 1A). On ocular examination, best-corrected visual acuity was 20/100 OD and 20/125 OS due to cataracts, pupils reacted normally without afferent pupillary defect, and ocular motility was full. She had mild proptosis in the right eye and right lower eyelid retraction. Orbicularis strength was intact and symmetric in both eyes. MRI of the orbits, face, and neck with and without contrast showed a 6.1 × 5.7 × 4.0-cm mass with erosion through the right sphenoid wing, involvement of the lacrimal gland, and abutment of the lateral rectus (Figure 1B). In discussing treatment strategies for the orbital component of the disease, the patient was strongly against an orbital exenteration. ### OUTPUT:

JAMA_FINAL105

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy man in his 60s presented to our department with an 8-month history of widespread pruritic papulonodular skin lesions on his extremities and trunk. The patient had been initially diagnosed with nodular prurigo at a local hospital and treated with various topical steroids and oral antihistamines for 2 months, without significant improvement. The skin lesions continued to progress and worsened after scratching. Physical examinations revealed disseminated erythematous papules, hypertrophic plaques approximately 1 to 2 cm in diameter, and dome-shaped nodules with excoriated whitish or pink centers on the scalp, chest, abdomen, back, waist, and extremities (Figure, A and B). Subsequent examinations of the mucosal membranes appeared normal. Other physical examinations as well as his medical and family histories were unremarkable. Peripheral eosinophils, serum total immunoglobulin E level, enzyme-linked immunosorbent assay (ELISA) test for HIV, and results of other routine laboratory tests were within normal ranges or negative. A biopsy specimen was taken from one of the skin lesions on his right forearm for histopathological examination and direct immunofluorescence (DIF) testing (Figure, C and D). ### OUTPUT:

Pemphigoid nodularis

['Dermatology', 'Geriatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy woman in her 60s presented to our department with an 8-month history of widespread pruritic papulonodular skin lesions on her extremities and trunk. The patient had been initially diagnosed with nodular prurigo at a local hospital and treated with various topical steroids and oral antihistamines for 2 months, without significant improvement. The skin lesions continued to progress and worsened after scratching. Physical examinations revealed disseminated erythematous papules, hypertrophic plaques approximately 1 to 2 cm in diameter, and dome-shaped nodules with excoriated whitish or pink centers on the scalp, chest, abdomen, back, waist, and extremities (Figure, A and B). Subsequent examinations of the mucosal membranes appeared normal. Other physical examinations as well as her medical and family histories were unremarkable. Peripheral eosinophils, serum total immunoglobulin E level, enzyme-linked immunosorbent assay (ELISA) test for HIV, and results of other routine laboratory tests were within normal ranges or negative. A biopsy specimen was taken from one of the skin lesions on her right forearm for histopathological examination and direct immunofluorescence (DIF) testing (Figure, C and D). ### OUTPUT:

JAMA_FINAL106

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 37-year-old Asian nonsmoking man with no known medical or drug history presented with an insidious onset of left-eye ptosis (only brought to attention by his friends on review of recent photographs) and subsequent painless vertical diplopia for 1 year. He did not complain of headaches, facial numbness, dysarthria, facial droop, dysphagia, or limb weakness or numbness. There was no history of joint pain or constitutional symptoms. Neurological examination revealed a nonfatigable partial left-eyelid ptosis, left-eye hypotropia at primary position, and impaired left eye supraduction (Figure 1) with a nonreactive left pupil on direct and consensual light reflexes. There were no other cranial nerve deficits. Limb reflexes, motor testing, and sensory testing results were normal, and the plantar responses were flexor. ### OUTPUT:

Neurovascular conflict of the oculomotor nerve

['Neurology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 37-year-old Asian nonsmoking woman with no known medical or drug history presented with an insidious onset of left-eye ptosis (only brought to attention by her friends on review of recent photographs) and subsequent painless vertical diplopia for 1 year. She did not complain of headaches, facial numbness, dysarthria, facial droop, dysphagia, or limb weakness or numbness. There was no history of joint pain or constitutional symptoms. Neurological examination revealed a nonfatigable partial left-eyelid ptosis, left-eye hypotropia at primary position, and impaired left eye supraduction (Figure 1) with a nonreactive left pupil on direct and consensual light reflexes. There were no other cranial nerve deficits. Limb reflexes, motor testing, and sensory testing results were normal, and the plantar responses were flexor. ### OUTPUT:

JAMA_FINAL107

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 15-year-old girl presented to the otorhinolaryngologic department for a right-side postauricular mass. The mass had been present since birth but had slowly grown larger in the previous 2 years. On physical examination, a 2.5 × 1.5-cm, nontender, blue, soft, cystic mass was observed in the right postauricular area. There were no fistular openings around the auricle or in the external auditory canal (EAC), and there were no additional cysts, sinuses, or fistulas at the right neck from the hyoid bone and chin to the EAC. On temporal bone computed tomography, a 2.5 × 1.5-cm, hypodense, oval-shaped cystic mass was revealed at the subcutaneous fat layer superoposterior to the right auricle. On temporal magnetic resonance imaging (MRI), an oval cystic mass was revealed at the same location, with high signal intensity on both T1-weighted and T2-weighted images and low signal intensity on enhanced T1-weighted fat suppression and T2-weighted short T1 inversion recovery images (Figure, A-D). In surgery, the well-demarcated cystic mass was completely excised. Yellowish fluid leaked out of the cyst during excision. On histopathologic examination, the cyst was lined by keratinizing stratified squamous epithelium with hair follicles and sebaceous glands. The cyst contained keratinous debris (Figure, E). There was no recurrence 6 months after surgery. ### OUTPUT:

Type 1 first branchial cleft cyst

['Otolaryngology', 'Pathology and Laboratory Medicine', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 15-year-old boy presented to the otorhinolaryngologic department for a right-side postauricular mass. The mass had been present since birth but had slowly grown larger in the previous 2 years. On physical examination, a 2.5 × 1.5-cm, nontender, blue, soft, cystic mass was observed in the right postauricular area. There were no fistular openings around the auricle or in the external auditory canal (EAC), and there were no additional cysts, sinuses, or fistulas at the right neck from the hyoid bone and chin to the EAC. On temporal bone computed tomography, a 2.5 × 1.5-cm, hypodense, oval-shaped cystic mass was revealed at the subcutaneous fat layer superoposterior to the right auricle. On temporal magnetic resonance imaging (MRI), an oval cystic mass was revealed at the same location, with high signal intensity on both T1-weighted and T2-weighted images and low signal intensity on enhanced T1-weighted fat suppression and T2-weighted short T1 inversion recovery images (Figure, A-D). In surgery, the well-demarcated cystic mass was completely excised. Yellowish fluid leaked out of the cyst during excision. On histopathologic examination, the cyst was lined by keratinizing stratified squamous epithelium with hair follicles and sebaceous glands. The cyst contained keratinous debris (Figure, E). There was no recurrence 6 months after surgery. ### OUTPUT:

JAMA_FINAL108

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 6-month-old girl presented to the emergency department for evaluation of fever and was noted to have mild inspiratory stridor. Her parents stated that her stridor began acutely at 4 months of age without any inciting illness or event. The stridor was worse with agitation but was without positional exacerbation. The family reported that the stridor had remained stable since onset. Her parents noted mild dysphagia but denied shortness of breath, cyanosis, or apnea. Laboratory test results revealed acute COVID-19 infection. Physical examination was unremarkable other than mild inspiratory stridor. Findings from bedside flexible laryngoscopy revealed intact vocal fold motion bilaterally with glottic competence. No supraglottic or glottic masses were identified. Anterior-posterior neck and chest radiography demonstrated narrowing and tortuosity of the trachea with displacement to the right proximal to the thoracic inlet and diffuse patchy heterogenous airspace opacities (Figure, A). Subsequent neck ultrasonography and computed tomography scan demonstrated a 3.2 × 2.0-cm low-density lesion abutting the trachea and hypopharynx at the level of thoracic inlet, with rightward displacement of the trachea and larynx (Figure, B-D). Operative laryngoscopy, bronchoscopy, and esophagoscopy revealed extrinsic compression of the trachea, right mainstem bronchus, and esophagus with rightward deviation of the trachea and esophagus. No mucosal tract was identified. ### OUTPUT:

Foregut duplication cyst

['Pediatrics', 'Otolaryngology', 'Swallowing and Dysphagia']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 6-month-old boy presented to the emergency department for evaluation of fever and was noted to have mild inspiratory stridor. His parents stated that his stridor began acutely at 4 months of age without any inciting illness or event. The stridor was worse with agitation but was without positional exacerbation. The family reported that the stridor had remained stable since onset. His parents noted mild dysphagia but denied shortness of breath, cyanosis, or apnea. Laboratory test results revealed acute COVID-19 infection. Physical examination was unremarkable other than mild inspiratory stridor. Findings from bedside flexible laryngoscopy revealed intact vocal fold motion bilaterally with glottic competence. No supraglottic or glottic masses were identified. Anterior-posterior neck and chest radiography demonstrated narrowing and tortuosity of the trachea with displacement to the right proximal to the thoracic inlet and diffuse patchy heterogenous airspace opacities (Figure, A). Subsequent neck ultrasonography and computed tomography scan demonstrated a 3.2 × 2.0-cm low-density lesion abutting the trachea and hypopharynx at the level of thoracic inlet, with rightward displacement of the trachea and larynx (Figure, B-D). Operative laryngoscopy, bronchoscopy, and esophagoscopy revealed extrinsic compression of the trachea, right mainstem bronchus, and esophagus with rightward deviation of the trachea and esophagus. No mucosal tract was identified. ### OUTPUT:

JAMA_FINAL109

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old woman with chronic hepatitis B infection and hepatocellular carcinoma (HCC) presented with subacute epigastric pain. Three years prior, she was diagnosed with a solitary HCC and underwent surgical resection with curative intent. Pathology revealed poorly differentiated HCC, 16 cm in largest dimension, with large vein involvement (T3bNXM0, R0 resection). The patient underwent expectant observation. One and a half years prior to the current presentation, laboratory results revealed an elevated α-fetoprotein (AFP), and cross-sectional imaging revealed multiple lung nodules consistent with metastases. She was treated with nivolumab every other week and attained a biochemical (baseline, 212.2 ng/dL; best response, 3.3 ng/dL) and radiographic complete response. In the current presentation, the patient reported nonradiating epigastric pain of moderate intensity for 1 month. Associated symptoms included nausea, anorexia, and water brash without emesis. Review of systems was positive for unchanged chronic abdominal bloating and negative for other constitutional or gastrointestinal symptoms. Laboratory results, including liver function tests, amylase, lipase, and AFP, were within normal limits, and hepatitis B virus polymerase chain reaction was undetectable. Computed tomography with multiphasic liver protocol showed new enlarged mesenteric nodes and diffuse thickening of the gastric body (Figure, A). Esophagogastroduodenoscopy (EGD) identified diffuse inflammation and ulcerations in the gastric body and antrum (Figure, B). Biopsy specimens showed chronic and active mixed inflammatory infiltrate, including intraepithelial lymphocytosis (Figure, C). No overt viral cytopathic effects were observed, and immunostaining results for Helicobacter pylori, cytomegalovirus, and adenovirus were negative. ### OUTPUT:

Immunotherapy-related gastritis

['Clinical Pharmacy and Pharmacology', 'Hepatobiliary Disease', 'Adverse Drug Events', 'Gastroenterology and Hepatology', 'Targeted and Immune Therapy']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old man with chronic hepatitis B infection and hepatocellular carcinoma (HCC) presented with subacute epigastric pain. Three years prior, he was diagnosed with a solitary HCC and underwent surgical resection with curative intent. Pathology revealed poorly differentiated HCC, 16 cm in largest dimension, with large vein involvement (T3bNXM0, R0 resection). The patient underwent expectant observation. One and a half years prior to the current presentation, laboratory results revealed an elevated α-fetoprotein (AFP), and cross-sectional imaging revealed multiple lung nodules consistent with metastases. He was treated with nivolumab every other week and attained a biochemical (baseline, 212.2 ng/dL; best response, 3.3 ng/dL) and radiographic complete response. In the current presentation, the patient reported nonradiating epigastric pain of moderate intensity for 1 month. Associated symptoms included nausea, anorexia, and water brash without emesis. Review of systems was positive for unchanged chronic abdominal bloating and negative for other constitutional or gastrointestinal symptoms. Laboratory results, including liver function tests, amylase, lipase, and AFP, were within normal limits, and hepatitis B virus polymerase chain reaction was undetectable. Computed tomography with multiphasic liver protocol showed new enlarged mesenteric nodes and diffuse thickening of the gastric body (Figure, A). Esophagogastroduodenoscopy (EGD) identified diffuse inflammation and ulcerations in the gastric body and antrum (Figure, B). Biopsy specimens showed chronic and active mixed inflammatory infiltrate, including intraepithelial lymphocytosis (Figure, C). No overt viral cytopathic effects were observed, and immunostaining results for Helicobacter pylori, cytomegalovirus, and adenovirus were negative. ### OUTPUT:

JAMA_FINAL110

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old patient was referred to the ear, nose, and throat department with left-sided hearing loss during the past 6 months without evident cause. He had a medical history of myocardial infarction, sleep apnea, Ménière disease, and congenital cataract. Furthermore, he did not report otalgia, otorrhea, a recent episode of Ménière disease, or other ear, nose, and throat or systemic symptoms. The patient used atorvastatin and acetylsalicylic acid, did not smoke, and reported drinking 2 glasses of wine daily. Otoscopy of the left ear revealed a yellow-whitish calcareous lobular mass located in the mesotympanum anterior to the malleus with an intact tympanic membrane. The lesion was hard and painful during palpation (Figure 1A). Otoscopy results for the right side were normal. ### OUTPUT:

Tophaceous gout

['Otolaryngology', 'Rheumatology', 'Otology', 'Audiology and Hearing']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old patient was referred to the ear, nose, and throat department with left-sided hearing loss during the past 6 months without evident cause. She had a medical history of myocardial infarction, sleep apnea, Ménière disease, and congenital cataract. Furthermore, she did not report otalgia, otorrhea, a recent episode of Ménière disease, or other ear, nose, and throat or systemic symptoms. The patient used atorvastatin and acetylsalicylic acid, did not smoke, and reported drinking 2 glasses of wine daily. Otoscopy of the left ear revealed a yellow-whitish calcareous lobular mass located in the mesotympanum anterior to the malleus with an intact tympanic membrane. The lesion was hard and painful during palpation (Figure 1A). Otoscopy results for the right side were normal. ### OUTPUT:

JAMA_FINAL111

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old woman with a 5-year history of intermittent bilateral uveitis and scleritis presented with painful left uveitis and an episcleral nodule (Figure 1). Ultrasound biomicroscopy revealed an elevated and tender uveal-episcleral lesion. Visual acuity was 20/30 in the left eye and 20/25 in the right eye. She had been taking 60 mg of oral prednisone; topical prednisolone acetate, 1%; and oral ibuprofen for 10 days without relief. She was suspected of being a steroid responder due to elevated intraocular pressure bilaterally. Three years prior, sinus pressure symptoms led to magnetic resonance imaging that revealed a nasal sinus mass. Biopsy demonstrated a histiocytic infiltrate with emperipolesis, consistent with Rosai-Dorfman-Destombes (RDD) disease. Timolol-dorzolamide topical drops were initiated. Staging evaluations showed no other sites of RDD disease. ### OUTPUT:

Episcleral-uveal nodule and uveitis associated with histiocytosis

['Hematology', 'Intraocular Inflammation', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old man with a 5-year history of intermittent bilateral uveitis and scleritis presented with painful left uveitis and an episcleral nodule (Figure 1). Ultrasound biomicroscopy revealed an elevated and tender uveal-episcleral lesion. Visual acuity was 20/30 in the left eye and 20/25 in the right eye. He had been taking 60 mg of oral prednisone; topical prednisolone acetate, 1%; and oral ibuprofen for 10 days without relief. He was suspected of being a steroid responder due to elevated intraocular pressure bilaterally. Three years prior, sinus pressure symptoms led to magnetic resonance imaging that revealed a nasal sinus mass. Biopsy demonstrated a histiocytic infiltrate with emperipolesis, consistent with Rosai-Dorfman-Destombes (RDD) disease. Timolol-dorzolamide topical drops were initiated. Staging evaluations showed no other sites of RDD disease. ### OUTPUT:

JAMA_FINAL112

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his mid-50s with a history of mitral valve repair presented to the emergency department with complaints of recent-onset palpitation within the last hour. On physical examination, the patient showed a rhythmic tachycardia with a rate of 178 beats/min and blood pressure of 130/80 mm Hg. The 12-lead electrocardiogram (ECG) revealed a regular tachycardia with a rate of 178 beats/min; no obvious P waves were recognizable (Figure 1A). The QRS complexes displayed 2 different morphologies occurring with a definite allorhythmic distribution: pairs of beats exhibiting complete right bundle branch block (RBBB) and QRS duration of 140 milliseconds followed by a third beat with normal configuration and QRS duration of 70 milliseconds. This trigeminal variation in intraventricular conduction occurred without any change in cycle length and was maintained. Adenosine administration quickly slowed the ventricular rate allowing recognition of an atrial tachycardia with a rate of 178/min and a 2:1 atrioventricular (AV) ratio (Figure 1B). ### OUTPUT:

Atypical atrial flutter with RBBB aberration and conduction improvement every third beat resulting from concealed type I (Wenckebach) second-degree block in the right bundle branch with 3:2 ratio

['Cardiology', 'Rhythm Disorders', 'Cardiothoracic Surgery', 'Surgery']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her mid-50s with a history of mitral valve repair presented to the emergency department with complaints of recent-onset palpitation within the last hour. On physical examination, the patient showed a rhythmic tachycardia with a rate of 178 beats/min and blood pressure of 130/80 mm Hg. The 12-lead electrocardiogram (ECG) revealed a regular tachycardia with a rate of 178 beats/min; no obvious P waves were recognizable (Figure 1A). The QRS complexes displayed 2 different morphologies occurring with a definite allorhythmic distribution: pairs of beats exhibiting complete right bundle branch block (RBBB) and QRS duration of 140 milliseconds followed by a third beat with normal configuration and QRS duration of 70 milliseconds. This trigeminal variation in intraventricular conduction occurred without any change in cycle length and was maintained. Adenosine administration quickly slowed the ventricular rate allowing recognition of an atrial tachycardia with a rate of 178/min and a 2:1 atrioventricular (AV) ratio (Figure 1B). ### OUTPUT:

JAMA_FINAL113

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 27-year-old White man presented with a recent onset of malaise, chills, night sweats, and sore throat with difficulty swallowing. He also reported redness of his right eye with watery discharge. He developed a skin rash affecting his trunk, limbs, and genitalia within the previous week. His medical history was noncontributory, except for allergic rhinitis, for which he was prescribed fexofenadrine pro re nata. His visual acuity was 6/6 in both eyes. Examination of his right eye revealed erythematous swollen eyelids. A slightly raised dome-shaped umbilicated nodule, of approximately 3 mm, was present on his medial one-third lower eyelid margin, with a similar lesion developing on the corresponding upper eyelid margin (Figure). A vesicular lesion was also present on the caruncle and there was global conjunctival hyperemia, mostly pronounced nasally and around the lesions (Figure, B). There were no signs of corneal involvement, and the anterior chamber was quiet. The left eye was normal. Results of fundus examination in both eyes were normal. No preauricular or submandibular lymph node involvement was noted, but cervical lymph nodes were enlarged. The pharynx was erythematous and swollen with white pus patches. The skin lesions were dome-shaped papules, round, pinkish-white in color, surrounded by an erythematous area. Full blood cell count and tests for HIV, AIDS, and syphilis were ordered. Conjunctival swabs and eyelid vesicle fluid were taken for polymerase chain reaction testing. Swabs of the upper respiratory tract were also taken. ### OUTPUT:

Ocular manifestation of Monkeypox infection

['Dermatology', 'External Eye Disease', 'Infectious Diseases', 'Ophthalmology', 'Mpox (Monkeypox)']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 27-year-old White woman presented with a recent onset of malaise, chills, night sweats, and sore throat with difficulty swallowing. She also reported redness of her right eye with watery discharge. She developed a skin rash affecting her trunk, limbs, and genitalia within the previous week. Her medical history was noncontributory, except for allergic rhinitis, for which she was prescribed fexofenadrine pro re nata. Her visual acuity was 6/6 in both eyes. Examination of her right eye revealed erythematous swollen eyelids. A slightly raised dome-shaped umbilicated nodule, of approximately 3 mm, was present on her medial one-third lower eyelid margin, with a similar lesion developing on the corresponding upper eyelid margin (Figure). A vesicular lesion was also present on the caruncle and there was global conjunctival hyperemia, mostly pronounced nasally and around the lesions (Figure, B). There were no signs of corneal involvement, and the anterior chamber was quiet. The left eye was normal. Results of fundus examination in both eyes were normal. No preauricular or submandibular lymph node involvement was noted, but cervical lymph nodes were enlarged. The pharynx was erythematous and swollen with white pus patches. The skin lesions were dome-shaped papules, round, pinkish-white in color, surrounded by an erythematous area. Full blood cell count and tests for HIV, AIDS, and syphilis were ordered. Conjunctival swabs and eyelid vesicle fluid were taken for polymerase chain reaction testing. Swabs of the upper respiratory tract were also taken. ### OUTPUT:

JAMA_FINAL114

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum. ### OUTPUT:

Eosinophilic fasciitis

['Neurology', 'Rheumatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 31-year-old woman with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, she found her palms could not make full contact with each other (the “prayer sign”). She had not been able to fully clench her fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on her limbs or trunk. No Raynaud phenomenon had occurred. Her medical and family histories were unremarkable. On examination, she showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum. ### OUTPUT:

JAMA_FINAL115

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits. Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B). ### OUTPUT:

Neuromuscular choristoma

['Facial Nerve', 'Facial Plastic Surgery', 'Head and Neck Cancer', 'Oncology', 'Head and Neck Surgery']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 21-year-old woman was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits. Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B). ### OUTPUT:

JAMA_FINAL116

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 18-year-old woman presented to the dermatology clinic for evaluation of recurrent skin, nail, and oral mucosal abnormalities. At age 4 years, she developed white oral plaques that resolved with oral nystatin. Approximately 6 months later, the oral plaques recurred, her toenails became thickened and yellowed, and red plaques appeared on both feet and lower legs. After 3 months of daily oral itraconazole, her skin, nail, and oral mucosal abnormalities resolved for approximately 1 year. Over the following years, she received intermittent 3- to 6-month courses of daily itraconazole for recurrent skin, nail, and oral mucosal abnormalities, which typically recurred within 6 to 12 months of discontinuing itraconazole. Her last dose of itraconazole was approximately 2 years prior to presentation. On physical examination, the patient had white, moist, nonadherent plaques in the oral mucosa and moist red fissures at bilateral oral commissures (Figure, left panel). She also had thickened, yellowed toenails and scaly erythematous plaques on her lower legs and feet bilaterally (Figure, right panel). Results of complete blood cell count with differential were normal, as were results of measurement of serum IgG, IgA, IgM, and IgE levels and analysis of CD3, CD4, and CD8 T-cell subsets. Potassium hydroxide wet mount preparation of skin scrapings from the lower extremities demonstrated fungal elements. Fungal culture of the skin scrapings grew Candida albicans. ### OUTPUT:

Chronic mucocutaneous candidiasis (CMC)

['Allergy and Clinical Immunology', 'Dermatology', 'Nail Disorders', 'Otolaryngology', 'Fungal Infections']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 18-year-old man presented to the dermatology clinic for evaluation of recurrent skin, nail, and oral mucosal abnormalities. At age 4 years, he developed white oral plaques that resolved with oral nystatin. Approximately 6 months later, the oral plaques recurred, his toenails became thickened and yellowed, and red plaques appeared on both feet and lower legs. After 3 months of daily oral itraconazole, his skin, nail, and oral mucosal abnormalities resolved for approximately 1 year. Over the following years, he received intermittent 3- to 6-month courses of daily itraconazole for recurrent skin, nail, and oral mucosal abnormalities, which typically recurred within 6 to 12 months of discontinuing itraconazole. His last dose of itraconazole was approximately 2 years prior to presentation. On physical examination, the patient had white, moist, nonadherent plaques in the oral mucosa and moist red fissures at bilateral oral commissures (Figure, left panel). He also had thickened, yellowed toenails and scaly erythematous plaques on his lower legs and feet bilaterally (Figure, right panel). Results of complete blood cell count with differential were normal, as were results of measurement of serum IgG, IgA, IgM, and IgE levels and analysis of CD3, CD4, and CD8 T-cell subsets. Potassium hydroxide wet mount preparation of skin scrapings from the lower extremities demonstrated fungal elements. Fungal culture of the skin scrapings grew Candida albicans. ### OUTPUT:

JAMA_FINAL117

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D). ### OUTPUT:

Keloidal scleroderma

['Rheumatology', 'Connective Tissue Disease of the Skin', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. She had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D). ### OUTPUT:

JAMA_FINAL118

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged. After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis. One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1). ### OUTPUT:

Recurrent retrobulbar hemorrhage owing to an orbital tumor: a primary orbital melanoma.

['Melanoma', 'Intraocular Tumors', 'Ophthalmology', 'Orbit']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged. After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis. One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1). ### OUTPUT:

JAMA_FINAL119

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development. ### OUTPUT:

Farber disease (disseminated lipogranuloma)

['Dermatology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 2-year-old male toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development. ### OUTPUT:

JAMA_FINAL120

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 74-year-old woman was referred for evaluation of retinal lesions in her left eye. Her ocular history was notable for recent cataract surgery 5 weeks prior to presentation that was complicated by endophthalmitis. A normal funduscopic examination was documented prior to cataract surgery. At the time of initial presentation to her local retina specialist 1 week following her cataract surgery, the patient had severe pain and redness. Her visual acuity was light perception. An examination revealed a 2-mm hypopyon and dense vitreous haze with no view of the retina. She was treated for presumed endophthalmitis with a vitreous tap and intravitreal injections of vancomycin (1 mg/0.1 mL), ceftazidime (2.2 mg/0.1 mL), and dexamethasone (0.4 mg/0.1 mL). The vitreous sample obtained at the time of treatment grew Staphylococcus caprae susceptible to vancomycin. At time of examination in our clinic 4 weeks following treatment, the patient was receiving topical steroid and cycloplegic drops. Her best-corrected visual acuity had improved to 20/70. Examination showed a deep and quiet anterior chamber with a well-positioned intraocular lens without any plaques or deposits on the lens capsule. Dilated ophthalmoscopic examination demonstrated improvement in the vitreous debris with 1+ vitritis and numerous superficial, round, white lesions spread throughout the fundus in all 4 quadrants and in the macula (Figure 1A). Optical coherence tomography verified the preretinal location of the lesions (Figure 1B). ### OUTPUT:

Vancomycin and ceftazidime deposits

['Cataract and Other Lens Disorders', 'Ophthalmology', 'Retinal Disorders', 'Antibiotic Use, Overuse, Resistance, Stewardship', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 74-year-old man was referred for evaluation of retinal lesions in his left eye. His ocular history was notable for recent cataract surgery 5 weeks prior to presentation that was complicated by endophthalmitis. A normal funduscopic examination was documented prior to cataract surgery. At the time of initial presentation to his local retina specialist 1 week following his cataract surgery, the patient had severe pain and redness. His visual acuity was light perception. An examination revealed a 2-mm hypopyon and dense vitreous haze with no view of the retina. He was treated for presumed endophthalmitis with a vitreous tap and intravitreal injections of vancomycin (1 mg/0.1 mL), ceftazidime (2.2 mg/0.1 mL), and dexamethasone (0.4 mg/0.1 mL). The vitreous sample obtained at the time of treatment grew Staphylococcus caprae susceptible to vancomycin. At time of examination in our clinic 4 weeks following treatment, the patient was receiving topical steroid and cycloplegic drops. His best-corrected visual acuity had improved to 20/70. Examination showed a deep and quiet anterior chamber with a well-positioned intraocular lens without any plaques or deposits on the lens capsule. Dilated ophthalmoscopic examination demonstrated improvement in the vitreous debris with 1+ vitritis and numerous superficial, round, white lesions spread throughout the fundus in all 4 quadrants and in the macula (Figure 1A). Optical coherence tomography verified the preretinal location of the lesions (Figure 1B). ### OUTPUT:

JAMA_FINAL121

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy 54-year-old woman presented with an erythematous right lower eyelid lesion with a vermiform appearance, accompanied by pruritus and pain (Figure 1A). The lesion resolved after 1 month, but she developed redness and swelling of the inner part of her right conjunctiva the next day (Figure 1B). She denied any vision changes, eye pain, eye discharge, or systemic symptoms, such as fevers, chills, night sweats, weight loss, or diarrhea. The patient had recently immigrated from rural Moldova 1 month prior to presentation, where she had exposure to farm animals, including dogs and cats. She had not traveled to any other countries. ### OUTPUT:

Ocular dirofilariasis

['External Eye Disease', 'Infectious Diseases', 'Ophthalmology', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy 54-year-old man presented with an erythematous right lower eyelid lesion with a vermiform appearance, accompanied by pruritus and pain (Figure 1A). The lesion resolved after 1 month, but he developed redness and swelling of the inner part of his right conjunctiva the next day (Figure 1B). He denied any vision changes, eye pain, eye discharge, or systemic symptoms, such as fevers, chills, night sweats, weight loss, or diarrhea. The patient had recently immigrated from rural Moldova 1 month prior to presentation, where he had exposure to farm animals, including dogs and cats. He had not traveled to any other countries. ### OUTPUT:

JAMA_FINAL122

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 79-year-old female patient presented with a 2-year history of asymptomatic erythematous-infiltrated patches and plaques on the right side of her scalp and face. The lesions gradually enlarged and coalesced into large plaques and nodules. Mild erosions occurred occasionally on the surface of the lesions. She denied having fever, fatigue, chills, night sweats, or weight loss. Physical examination demonstrated ill-defined, indurated erythematous-violaceous patches, nodules, and plaques involving the surface of her head and face with sporadic erosion and brownish crusts (Figure, A). The findings of systemic reviews were unremarkable, and there was no lymphadenopathy. The complete blood cell count revealed normal white blood cell count. The biopsy from an erythematous nodule displayed sheets of medium to large mononuclear cells infiltrated in the dermis, some of which filled and expanded apparent dermal blood vessels and had large, irregular, pleomorphic nuclei (Figure, B). In addition, some neoplastic cells formed a balloon appearance. No epidermotrophism was found. The initial immunohistochemical stain revealed the tumor cells were positive for CD3 and negative for CD20, AE1/AE3, CK20, chromogranin A, and melan-A. The Ki-67 labeling index was 70%. ### OUTPUT:

Intravascular anaplastic large cell lymphoma

['Dermatology', 'Oncology', 'Soft-Tissue Tumors', 'Lymphomas']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 79-year-old male patient presented with a 2-year history of asymptomatic erythematous-infiltrated patches and plaques on the right side of his scalp and face. The lesions gradually enlarged and coalesced into large plaques and nodules. Mild erosions occurred occasionally on the surface of the lesions. He denied having fever, fatigue, chills, night sweats, or weight loss. Physical examination demonstrated ill-defined, indurated erythematous-violaceous patches, nodules, and plaques involving the surface of his head and face with sporadic erosion and brownish crusts (Figure, A). The findings of systemic reviews were unremarkable, and there was no lymphadenopathy. The complete blood cell count revealed normal white blood cell count. The biopsy from an erythematous nodule displayed sheets of medium to large mononuclear cells infiltrated in the dermis, some of which filled and expanded apparent dermal blood vessels and had large, irregular, pleomorphic nuclei (Figure, B). In addition, some neoplastic cells formed a balloon appearance. No epidermotrophism was found. The initial immunohistochemical stain revealed the tumor cells were positive for CD3 and negative for CD20, AE1/AE3, CK20, chromogranin A, and melan-A. The Ki-67 labeling index was 70%. ### OUTPUT:

JAMA_FINAL123

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 11-year-old boy was referred to assess a retinal mass in the left eye found on his first routine ophthalmic evaluation. He reported no present or past ocular symptoms and had negative findings on a review of systems. His history included full-term birth by cesarean delivery from an uncomplicated pregnancy. He had healthy, nonconsanguineous parents. The ocular examination showed a visual acuity of 20/20 OU with no anterior segment abnormalities. Findings of dilated fundus examination of the right eye were within normal limits. In the left eye, a white, translucent solid lesion with calcification was noticeable in the inferonasal quadrant (Figure, A). The lesion measured approximately 1.6 mm in height, exhibited mild underlying chorioretinal changes, and had associated 3 vitreous seeds (Figure, A). There were no signs of internal vascularization or vitritis. Optical coherence tomography confirmed an intraretinal location and calcified deposits within the lesion (Figure, B). ### OUTPUT:

Retinoma

['Ophthalmology', 'Pediatrics', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 11-year-old girl was referred to assess a retinal mass in the left eye found on her first routine ophthalmic evaluation. She reported no present or past ocular symptoms and had negative findings on a review of systems. Her history included full-term birth by cesarean delivery from an uncomplicated pregnancy. She had healthy, nonconsanguineous parents. The ocular examination showed a visual acuity of 20/20 OU with no anterior segment abnormalities. Findings of dilated fundus examination of the right eye were within normal limits. In the left eye, a white, translucent solid lesion with calcification was noticeable in the inferonasal quadrant (Figure, A). The lesion measured approximately 1.6 mm in height, exhibited mild underlying chorioretinal changes, and had associated 3 vitreous seeds (Figure, A). There were no signs of internal vascularization or vitritis. Optical coherence tomography confirmed an intraretinal location and calcified deposits within the lesion (Figure, B). ### OUTPUT:

JAMA_FINAL124

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy man in his early 70s presented to the Department of Dermatology with a 2-year history of a mildly pruritic, erythematous, and gradually enlarging lesion on the proximal portion of his left calf. The lesion had appeared without an identifiable cause, and for the previous 2 months, the patient had applied topical corticosteroids and antifungals with no improvement. Physical examination revealed an ill-defined, nonindurated, erythematous-violaceous plaque that was slightly raised but with an atrophic appearance (Figure, A). A skin biopsy was obtained for histopathology examination (Figure, B-D). ### OUTPUT:

Poikilodermatous plaque–like hemangioma

['Geriatrics', 'Cutaneous Vascular Malformations', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy woman in her early 70s presented to the Department of Dermatology with a 2-year history of a mildly pruritic, erythematous, and gradually enlarging lesion on the proximal portion of her left calf. The lesion had appeared without an identifiable cause, and for the previous 2 months, the patient had applied topical corticosteroids and antifungals with no improvement. Physical examination revealed an ill-defined, nonindurated, erythematous-violaceous plaque that was slightly raised but with an atrophic appearance (Figure, A). A skin biopsy was obtained for histopathology examination (Figure, B-D). ### OUTPUT:

JAMA_FINAL125

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old man with history of cutaneous melanoma of the trunk was referred for evaluation of a pigmented angle lesion in the right eye. He denied any changes in vision, flashes, floaters, eye pain, or eye redness. He denied a history of trauma, intraocular surgery, or inflammation in the eyes. He had a history of stage 3B melanoma treated with ipilimumab complicated by grade 3 colitis refractory to high-dose corticosteroids and infliximab requiring colectomy and stomal hernia after hernia repair. Serial positron emission tomography/computed tomography scans showed no evidence of metabolically active disease. His medical history was notable for hypertension controlled with metoprolol. His mother had a history of breast cancer but otherwise family history was unremarkable. Visual acuity was 20/20 OD and 20/25 OS. Intraocular pressure was 16 mm Hg OD and 15 mm Hg OS. Anterior segment examination showed inferior corneal endothelial pigmentation in the right eye (Figure, A) and trace nuclear sclerotic cataracts in both eyes. He did not have ectropion uvea, corectopia, or feeder vessels. Dilated ophthalmoscopy was unremarkable. Four-mirror gonioscopy in the right eye showed an open angle, normally pigmented trabecular meshwork, and a well-demarcated pigmented brown lesion without extension into the angle (Figure, B). Ultrasound biomicroscopy (UBM) in the right eye was unremarkable and did not show any masses. ### OUTPUT:

Peripheral pigmented placoid corneal endotheliopathy

['Dermatology', 'Oncology', 'Skin Cancer', 'Melanoma', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old woman with history of cutaneous melanoma of the trunk was referred for evaluation of a pigmented angle lesion in the right eye. She denied any changes in vision, flashes, floaters, eye pain, or eye redness. She denied a history of trauma, intraocular surgery, or inflammation in the eyes. She had a history of stage 3B melanoma treated with ipilimumab complicated by grade 3 colitis refractory to high-dose corticosteroids and infliximab requiring colectomy and stomal hernia after hernia repair. Serial positron emission tomography/computed tomography scans showed no evidence of metabolically active disease. Her medical history was notable for hypertension controlled with metoprolol. Her mother had a history of breast cancer but otherwise family history was unremarkable. Visual acuity was 20/20 OD and 20/25 OS. Intraocular pressure was 16 mm Hg OD and 15 mm Hg OS. Anterior segment examination showed inferior corneal endothelial pigmentation in the right eye (Figure, A) and trace nuclear sclerotic cataracts in both eyes. She did not have ectropion uvea, corectopia, or feeder vessels. Dilated ophthalmoscopy was unremarkable. Four-mirror gonioscopy in the right eye showed an open angle, normally pigmented trabecular meshwork, and a well-demarcated pigmented brown lesion without extension into the angle (Figure, B). Ultrasound biomicroscopy (UBM) in the right eye was unremarkable and did not show any masses. ### OUTPUT:

JAMA_FINAL127

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old woman with a history of intravenous heroin use and chronic inactive hepatitis B virus (HBV) infection with a low serum HBV DNA value, normal liver enzyme values, and no evidence of cirrhosis presented to the emergency department with sudden onset of painless jaundice and 8 days of malaise. Her last intravenous heroin use occurred 9 days prior to presentation. She was not taking any prescription or herbal medications and had not been prescribed suppressive antiviral medication for chronic HBV infection. She reported no history of travel outside the US and no raw meat ingestion. Her vital signs, mentation, and physical examination were normal except for scleral icterus (Figure). Results of blood testing were negative for hepatitis C virus RNA, anti–hepatitis A IgM, and HIV antibody. Other selected laboratory values are shown in the Table. A liver ultrasound performed 6 months prior to presentation and a repeat liver ultrasound with Doppler revealed no abnormalities. ### OUTPUT:

Hepatitis D superinfection

['Infectious Diseases', 'Hepatitis B', 'Hepatobiliary Disease', 'Gastroenterology and Hepatology', 'Viral Hepatitis']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old man with a history of intravenous heroin use and chronic inactive hepatitis B virus (HBV) infection with a low serum HBV DNA value, normal liver enzyme values, and no evidence of cirrhosis presented to the emergency department with sudden onset of painless jaundice and 8 days of malaise. His last intravenous heroin use occurred 9 days prior to presentation. He was not taking any prescription or herbal medications and had not been prescribed suppressive antiviral medication for chronic HBV infection. He reported no history of travel outside the US and no raw meat ingestion. His vital signs, mentation, and physical examination were normal except for scleral icterus (Figure). Results of blood testing were negative for hepatitis C virus RNA, anti–hepatitis A IgM, and HIV antibody. Other selected laboratory values are shown in the Table. A liver ultrasound performed 6 months prior to presentation and a repeat liver ultrasound with Doppler revealed no abnormalities. ### OUTPUT:

JAMA_FINAL128

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 2-month-old, full-term female presented with a left upper neck mass that was first noted at birth. Her parents reported no fevers, constitutional symptoms, or enlargement of the mass. On physical examination, there was a nontender 4-cm mass in the left submandibular region with no overlying skin changes. Ultrasonography results showed an avascular cystic structure with internal debris and a single thin septation. Contrast-enhanced computed tomography (CT) of the neck soft tissue revealed a 3-cm low attenuation, nonenhancing, cystic-appearing mass that elevated the submandibular gland to the level of the parapharyngeal fat space with medial extension of the lesion into the tongue musculature. The walls were thin except for mildly thickened capsule along the posterior aspect of the lesion (Figure, A and B). Fluid that aspirated from the cyst was serous, and cytology showed mature and anucleate squamous cells with acute inflammation. The mass returned after 3 weeks. Further analysis 8 months after the initial CT via contrast-enhanced magnetic resonance imaging (MRI) showed a large, multiseptated cystic structure (Figure, C); the capsule of the wall was mildly thickened and was contrast enhancing. At age 12 months, the mass was excised via neck dissection. A lateral component at the level of the sternocleidomastoid muscle was completely excised. An intraoperative rupture of the thin capsule caused some spillage of cystic contents that were milky white in some areas and mucinous in others. ### OUTPUT:

Foregut duplication cyst

['Congenital Defects', 'Otolaryngology', 'Pediatrics', 'Head and Neck Surgery']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 2-month-old, full-term male presented with a left upper neck mass that was first noted at birth. His parents reported no fevers, constitutional symptoms, or enlargement of the mass. On physical examination, there was a nontender 4-cm mass in the left submandibular region with no overlying skin changes. Ultrasonography results showed an avascular cystic structure with internal debris and a single thin septation. Contrast-enhanced computed tomography (CT) of the neck soft tissue revealed a 3-cm low attenuation, nonenhancing, cystic-appearing mass that elevated the submandibular gland to the level of the parapharyngeal fat space with medial extension of the lesion into the tongue musculature. The walls were thin except for mildly thickened capsule along the posterior aspect of the lesion (Figure, A and B). Fluid that aspirated from the cyst was serous, and cytology showed mature and anucleate squamous cells with acute inflammation. The mass returned after 3 weeks. Further analysis 8 months after the initial CT via contrast-enhanced magnetic resonance imaging (MRI) showed a large, multiseptated cystic structure (Figure, C); the capsule of the wall was mildly thickened and was contrast enhancing. At age 12 months, the mass was excised via neck dissection. A lateral component at the level of the sternocleidomastoid muscle was completely excised. An intraoperative rupture of the thin capsule caused some spillage of cystic contents that were milky white in some areas and mucinous in others. ### OUTPUT:

JAMA_FINAL129

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 32-year-old woman who was admitted to the hospital for fever, flulike symptoms, and altered mental status developed sudden-onset blurry vision in her right eye. Her history was notable for phthisis in her left eye due to a left orbit clear cell sarcoma with metastatic disease, after surgical excision and radiation, with recent enrollment in a palliative immunotherapy research protocol. After completing 2 days of broad-spectrum intravenous antibiotics and antivirals for presumed septic meningitis, her laboratory and imaging results returned negative and she was transitioned to intravenous methylprednisolone (1 mg/kg). One day later, her mental status improved, and she reported central blurry vision in her right eye. On examination, her visual acuity was 20/40 in this eye, she had normal intraocular pressure, and there was no evidence of anterior chamber or vitreous cells. Dilated fundus examination revealed segmental areas of venous sheathing (Figure 1A) in the right eye and was not possible in the left eye owing to phthisis. An optical coherence tomography scan of the right eye revealed hyperreflective changes along the outer plexiform and outer nuclear layers, small intraretinal cysts, and disruption of the ellipsoid and especially the interdigitation zone (Figure 1B). ### OUTPUT:

Atezolizumab-associated retinopathy

['Targeted and Immune Therapy', 'Oncology', 'Ophthalmology', 'Sarcomas', 'Adverse Drug Events']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 32-year-old man who was admitted to the hospital for fever, flulike symptoms, and altered mental status developed sudden-onset blurry vision in his right eye. His history was notable for phthisis in his left eye due to a left orbit clear cell sarcoma with metastatic disease, after surgical excision and radiation, with recent enrollment in a palliative immunotherapy research protocol. After completing 2 days of broad-spectrum intravenous antibiotics and antivirals for presumed septic meningitis, his laboratory and imaging results returned negative and he was transitioned to intravenous methylprednisolone (1 mg/kg). One day later, his mental status improved, and he reported central blurry vision in his right eye. On examination, his visual acuity was 20/40 in this eye, he had normal intraocular pressure, and there was no evidence of anterior chamber or vitreous cells. Dilated fundus examination revealed segmental areas of venous sheathing (Figure 1A) in the right eye and was not possible in the left eye owing to phthisis. An optical coherence tomography scan of the right eye revealed hyperreflective changes along the outer plexiform and outer nuclear layers, small intraretinal cysts, and disruption of the ellipsoid and especially the interdigitation zone (Figure 1B). ### OUTPUT:

JAMA_FINAL130

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An adolescent girl presented with an asymptomatic slightly reddish verrucous plaque on the right temple. The skin lesion was nail sized when first noticed 1½ years earlier, then gradually developed over the 8 months prior to presentation. The patient denied any associated fevers, weight loss, or night sweats. Physical examination revealed a slightly reddish verrucous mass with translucent papules and plaques on the right temple, about 5 cm in diameter, with surface hemorrhagic crust in the side adjacent to right eyebrow arch (Figure, A). The lesion was nontender with no purulent discharge and no severe necrotic changes. There was no hepatosplenomegaly or superficial lymphadenopathy. Laboratory tests, including blood cell counts, urinalysis, and kidney and hepatic panels, revealed no abnormalities. A skin biopsy was performed and submitted for histopathologic analysis (Figure, B-D). ### OUTPUT:

Primary cutaneous embryonal rhabdomyosarcoma

['Oncology', 'Pediatrics', 'Sarcomas', 'Soft-Tissue Tumors', 'Adolescent Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An adolescent boy presented with an asymptomatic slightly reddish verrucous plaque on the right temple. The skin lesion was nail sized when first noticed 1½ years earlier, then gradually developed over the 8 months prior to presentation. The patient denied any associated fevers, weight loss, or night sweats. Physical examination revealed a slightly reddish verrucous mass with translucent papules and plaques on the right temple, about 5 cm in diameter, with surface hemorrhagic crust in the side adjacent to right eyebrow arch (Figure, A). The lesion was nontender with no purulent discharge and no severe necrotic changes. There was no hepatosplenomegaly or superficial lymphadenopathy. Laboratory tests, including blood cell counts, urinalysis, and kidney and hepatic panels, revealed no abnormalities. A skin biopsy was performed and submitted for histopathologic analysis (Figure, B-D). ### OUTPUT:

JAMA_FINAL131

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 40s with a long-standing history of poorly controlled HIV (multiple treatment lapses, viral load of 22 871 copies/mL 8 months prior to presentation but now undetectable with use of highly active antiretroviral therapy, with a CD4 count of 40 cells/mm3) presented to the emergency department with nausea, abdominal pain, bloody stools, odynophagia, and recurrent oral and perianal ulcers and was found to have pancytopenia and septic shock. During admission in the intensive care unit, treatment with broad-spectrum oral antibiotics for presumed infection and oral fluconazole for thrush led to improvement in the patient’s medical condition, but the ulcers persisted. Dermatology was consulted for input on the cause of the ulcers, which had been ongoing for approximately 6 months prior; individual lesions lasted 1 to 3 weeks before self-resolving. Biopsy of an oral mucosal lesion performed 1 month earlier had shown nonspecific inflammation. Examination revealed exquisitely tender, ovoid, punched-out ulcerations of the inferior lip and scrapeable white plaques on the tongue (Figure, A), right buccal mucosa, and external anal mucosa (Figure, B). A punch biopsy from 1 of the perianal ulcers was performed (Figure, C and D). ### OUTPUT:

Epstein-Barr virus–positive mucocutaneous ulcers

['Dermatology', 'Emergency Medicine', 'HIV', 'Infectious Diseases', 'Critical Care Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 40s with a long-standing history of poorly controlled HIV (multiple treatment lapses, viral load of 22 871 copies/mL 8 months prior to presentation but now undetectable with use of highly active antiretroviral therapy, with a CD4 count of 40 cells/mm3) presented to the emergency department with nausea, abdominal pain, bloody stools, odynophagia, and recurrent oral and perianal ulcers and was found to have pancytopenia and septic shock. During admission in the intensive care unit, treatment with broad-spectrum oral antibiotics for presumed infection and oral fluconazole for thrush led to improvement in the patient’s medical condition, but the ulcers persisted. Dermatology was consulted for input on the cause of the ulcers, which had been ongoing for approximately 6 months prior; individual lesions lasted 1 to 3 weeks before self-resolving. Biopsy of an oral mucosal lesion performed 1 month earlier had shown nonspecific inflammation. Examination revealed exquisitely tender, ovoid, punched-out ulcerations of the inferior lip and scrapeable white plaques on the tongue (Figure, A), right buccal mucosa, and external anal mucosa (Figure, B). A punch biopsy from 1 of the perianal ulcers was performed (Figure, C and D). ### OUTPUT:

JAMA_FINAL132

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his early 20s presented with suspected syncope and shaking with no significant medical history. The patient fell asleep and his girlfriend tried to wake him, but he started shaking and slumped over on the ground. He denied confusion afterward but did not feel well with nausea, flushing, chest tightness, and a rapid heart rate. About 10 minutes later, he had a second syncopal episode for 2 to 3 minutes with more than 20 muscle jerks. On presentation at the emergency department, he was afebrile, blood pressure was 120/59 mm Hg, heart rate was 85 beats per min, respiratory rate was 16 breaths per min, and oxygen saturation was 96% on room air. His cardiac examination revealed normal heart sounds with no murmurs. The electrocardiogram (ECG) was performed early on arrival in the emergency department (Figure). Transthoracic echocardiography revealed an ejection fraction of 54%, mild right ventricular (RV) dilation (RV diameter, 4.1 cm), and no significant valvular abnormalities. Cardiac magnetic resonance imaging showed no RV abnormalities and qualitatively normal RV function. Neurology consultation was obtained with concern for an epileptic seizure event surrounding the recurrent syncopal episodes. Brain magnetic resonance imaging and electroencephalogram were obtained, both of which results were normal. On further questioning, patient reported having a second cousin with sudden cardiac death of uncertain etiology in his early 20s. ### OUTPUT:

Brugada type 1 syndrome with unexplained syncope

['Neurology', 'Cardiology', 'Rhythm Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her early 20s presented with suspected syncope and shaking with no significant medical history. The patient fell asleep and her boyfriend tried to wake her, but she started shaking and slumped over on the ground. She denied confusion afterward but did not feel well with nausea, flushing, chest tightness, and a rapid heart rate. About 10 minutes later, she had a second syncopal episode for 2 to 3 minutes with more than 20 muscle jerks. On presentation at the emergency department, she was afebrile, blood pressure was 120/59 mm Hg, heart rate was 85 beats per min, respiratory rate was 16 breaths per min, and oxygen saturation was 96% on room air. Her cardiac examination revealed normal heart sounds with no murmurs. The electrocardiogram (ECG) was performed early on arrival in the emergency department (Figure). Transthoracic echocardiography revealed an ejection fraction of 54%, mild right ventricular (RV) dilation (RV diameter, 4.1 cm), and no significant valvular abnormalities. Cardiac magnetic resonance imaging showed no RV abnormalities and qualitatively normal RV function. Neurology consultation was obtained with concern for an epileptic seizure event surrounding the recurrent syncopal episodes. Brain magnetic resonance imaging and electroencephalogram were obtained, both of which results were normal. On further questioning, patient reported having a second cousin with sudden cardiac death of uncertain etiology in her early 20s. ### OUTPUT:

JAMA_FINAL133

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 32-year-old Black woman presented with a 1-year history of facial swelling, predominantly in the right preauricular and left submandibular regions. Her symptoms began after relocation to California and occurred more frequently at her home. However, she could not discern any environmental or dietary triggers. She reported pruritus and swelling, which were usually moderate but occasionally severe, prompting several emergency department visits. During an emergency department visit, she was diagnosed with acute parotitis based on clinical and radiographic findings of diffuse gland edema, without salivary stones or masses. Her symptoms responded to oral prednisone bursts and diphenhydramine, but not to second-generation antihistamines or montelukast. Her workup included immune serology and total immunoglobulin (Ig) E measurements, all of which were within normal limits. A differential blood cell count revealed 10% eosinophils (normal, <6%) and an absolute eosinophil count 500/µL (to convert to ×109/L, multiply by 0.001). Titers for antinuclear antibodies, rheumatoid factor, anti-Ro (SS-A), and anti-La (SS-B) were negative. Sialendoscopy of her right parotid and left submandibular glands found no obstructing stones or strictures. Concurrent steroid irrigation did not provide any substantial benefit. An open biopsy of the right parotid tail revealed nonspecific inflammatory changes and otherwise normal parenchyma. Given the frequency and severity of her symptoms along with multiple treatment failures, she opted to undergo a right superficial parotidectomy, which proceeded without complications. Further histologic examination of the surgical specimen revealed substantial periductal inflammatory infiltrate with eosinophils, as seen in the Figure. ### OUTPUT:

Eosinophilic sialodochitis

['Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 32-year-old Black man presented with a 1-year history of facial swelling, predominantly in the right preauricular and left submandibular regions. His symptoms began after relocation to California and occurred more frequently at his home. However, he could not discern any environmental or dietary triggers. He reported pruritus and swelling, which were usually moderate but occasionally severe, prompting several emergency department visits. During an emergency department visit, he was diagnosed with acute parotitis based on clinical and radiographic findings of diffuse gland edema, without salivary stones or masses. His symptoms responded to oral prednisone bursts and diphenhydramine, but not to second-generation antihistamines or montelukast. His workup included immune serology and total immunoglobulin (Ig) E measurements, all of which were within normal limits. A differential blood cell count revealed 10% eosinophils (normal, <6%) and an absolute eosinophil count 500/µL (to convert to ×109/L, multiply by 0.001). Titers for antinuclear antibodies, rheumatoid factor, anti-Ro (SS-A), and anti-La (SS-B) were negative. Sialendoscopy of his right parotid and left submandibular glands found no obstructing stones or strictures. Concurrent steroid irrigation did not provide any substantial benefit. An open biopsy of the right parotid tail revealed nonspecific inflammatory changes and otherwise normal parenchyma. Given the frequency and severity of his symptoms along with multiple treatment failures, he opted to undergo a right superficial parotidectomy, which proceeded without complications. Further histologic examination of the surgical specimen revealed substantial periductal inflammatory infiltrate with eosinophils, as seen in the Figure. ### OUTPUT:

JAMA_FINAL134

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 78-year-old White man was referred to our clinic for evaluation of an unexplained subjective decrease in vision for more than 6 months, more pronounced in the right eye, and insufficiently controlled intraocular pressure (IOP). Local antiglaucoma therapy with a fixed-combination prostaglandin and β-blocker was used regularly in both eyes owing to long-standing primary open-angle glaucoma. Uneventful cataract surgery with phacoemulsification and in-the-bag insertion of an intraocular lens was performed 10 years earlier in both eyes. Best corrected visual acuity (BCVA) was 1.0 and 0.5 (Snellen equivalent, 20/20 and 20/40) OD and OS, respectively. His manifest refraction revealed a difference of −0.75 D sphere compared with his own preexisting glasses in the right eye. IOP was 24 mm Hg in the right eye and 18 mm Hg in the left eye. Slitlamp examination revealed a milky substance in the retrolental space, more pronounced in the right eye (Figure) but evident in both. The rest of the slitlamp examination was unremarkable with moderate superficial punctate keratitis owing to ocular surface disease, an anterior chamber depth of Van Herick grade 4 (peripheral anterior chamber depth >1 corneal thickness), an absence of anterior chamber inflammation, and a moderate amount of Elschnig pearls in both eyes. ### OUTPUT:

Late-onset postoperative capsular bag distension syndrome

['Cataract and Other Lens Disorders', 'Glaucoma', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Late-onset postoperative capsular bag distension syndrome. Case report: A 78-year-old White woman was referred to our clinic for evaluation of an unexplained subjective decrease in vision for more than 6 months, more pronounced in the right eye, and insufficiently controlled intraocular pressure (IOP). Local antiglaucoma therapy with a fixed-combination prostaglandin and β-blocker was used regularly in both eyes owing to long-standing primary open-angle glaucoma. Uneventful cataract surgery with phacoemulsification and in-the-bag insertion of an intraocular lens was performed 10 years earlier in both eyes. Best corrected visual acuity (BCVA) was 1.0 and 0.5 (Snellen equivalent, 20/20 and 20/40) OD and OS, respectively. Her manifest refraction revealed a difference of −0.75 D sphere compared with her own preexisting glasses in the right eye. IOP was 24 mm Hg in the right eye and 18 mm Hg in the left eye. Slitlamp examination revealed a milky substance in the retrolental space, more pronounced in the right eye (Figure) but evident in both. The rest of the slitlamp examination was unremarkable with moderate superficial punctate keratitis owing to ocular surface disease, an anterior chamber depth of Van Herick grade 4 (peripheral anterior chamber depth >1 corneal thickness), an absence of anterior chamber inflammation, and a moderate amount of Elschnig pearls in both eyes. ### OUTPUT:

JAMA_FINAL135

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old US-born man with a history of cataract surgery in both eyes 3 years ago presented with worsening blurriness, photopsia, floaters, and intermittent eye redness for the past year, worse in the left eye. He was otherwise well. The referring physician was treating him with prednisolone eye drops for cystoid macular edema after recent left Nd:YAG capsulotomy. His best-corrected visual acuity was 20/20 OD and 20/30 OS with intraocular pressures of 20 mm Hg OD and 26 mm Hg OS. The anterior segments showed well-positioned posterior chamber intraocular lens implants with open posterior capsules. Dilated fundus examination revealed a small peripheral hypoautofluorescent chorioretinal scar in the right eye. In the left eye, there was trace vitreous haze and 2+ anterior vitreous cell. Multifocal chorioretinal scars extended from the left optic nerve into the macula in each quadrant (Figure 1). These lesions showed variable hypoautofluorescence and hyperautofluorescence. On indocyanine green angiography (ICGA), the confluent hypoautofluorescent lesions showed loss of the choriocapillaris and prominent large choroidal vessels, whereas the mottled hypoautofluorescence and hyperautofluorescent lesions appeared to block the underlying fluorescence. Routine laboratory testing was unremarkable except for a positive interferon-gamma release assay for Mycobacterium tuberculosis. A chest radiograph was normal. ### OUTPUT:

Tuberculous serpiginouslike choroiditis

['Infectious Diseases', 'Macular Diseases', 'Ophthalmology', 'Tuberculosis', 'Choroidal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old US-born woman with a history of cataract surgery in both eyes 3 years ago presented with worsening blurriness, photopsia, floaters, and intermittent eye redness for the past year, worse in the left eye. She was otherwise well. The referring physician was treating her with prednisolone eye drops for cystoid macular edema after recent left Nd:YAG capsulotomy. Her best-corrected visual acuity was 20/20 OD and 20/30 OS with intraocular pressures of 20 mm Hg OD and 26 mm Hg OS. The anterior segments showed well-positioned posterior chamber intraocular lens implants with open posterior capsules. Dilated fundus examination revealed a small peripheral hypoautofluorescent chorioretinal scar in the right eye. In the left eye, there was trace vitreous haze and 2+ anterior vitreous cell. Multifocal chorioretinal scars extended from the left optic nerve into the macula in each quadrant (Figure 1). These lesions showed variable hypoautofluorescence and hyperautofluorescence. On indocyanine green angiography (ICGA), the confluent hypoautofluorescent lesions showed loss of the choriocapillaris and prominent large choroidal vessels, whereas the mottled hypoautofluorescence and hyperautofluorescent lesions appeared to block the underlying fluorescence. Routine laboratory testing was unremarkable except for a positive interferon-gamma release assay for Mycobacterium tuberculosis. A chest radiograph was normal. ### OUTPUT:

JAMA_FINAL136

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old woman with a history of metastatic neuroendocrine carcinoid tumor (NET) status in remission after liver transplant was hospitalized for workup of a new pancreatic mass concerning for recurrence. Several days into her hospital course, she developed acute-onset severe bilateral periorbital swelling, chemosis, and ophthalmoplegia as well as occasional flushing and palpitations. Her best-corrected visual acuity was 20/70 in both eyes. Pupils, intraocular pressure, and color vision were normal. She had bilateral proptosis to 20/21 mm by Hertel exophthalmometer, −3 restriction of extraocular movements in all directions of gaze, diffuse punctate epithelial erosions, and mechanical lower lid entropion secondary to severe chemosis in both eyes (Figure 1A). Anterior segment examination and dilated ophthalmoscopy results were otherwise unremarkable. ### OUTPUT:

Recurrent NET metastatic to the EOMs

['Ophthalmology', 'Oncology', 'Surgery', 'Surgical Oncology', 'External Eye Disease']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old man with a history of metastatic neuroendocrine carcinoid tumor (NET) status in remission after liver transplant was hospitalized for workup of a new pancreatic mass concerning for recurrence. Several days into his hospital course, he developed acute-onset severe bilateral periorbital swelling, chemosis, and ophthalmoplegia as well as occasional flushing and palpitations. His best-corrected visual acuity was 20/70 in both eyes. Pupils, intraocular pressure, and color vision were normal. He had bilateral proptosis to 20/21 mm by Hertel exophthalmometer, −3 restriction of extraocular movements in all directions of gaze, diffuse punctate epithelial erosions, and mechanical lower lid entropion secondary to severe chemosis in both eyes (Figure 1A). Anterior segment examination and dilated ophthalmoscopy results were otherwise unremarkable. ### OUTPUT:

JAMA_FINAL137

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 60s with a history of hypertension and hyperlipidemia presented to dermatology clinic with a 4-month history of fatigue, night sweats, and weight loss and 2 months of enlarging lesions on his scalp and hands. He reported no new medications or recent infection. His temperature was 37.5 °C (99.5 °F); heart rate, 102/min; blood pressure, 98/72 mm Hg; respiratory rate, 12/min; and oxygen saturation, 94% on room air. His skin examination revealed 3 tender, nonfluctuant 10-cm scalp plaques with overlying hemorrhagic crust and necrosis on an erythematous indurated base (Figure, left panel). Similar-appearing papules and plaques were present on the dorsal surfaces of his hands. The remainder of his physical examination was normal. ### OUTPUT:

Sweet syndrome with myelodysplastic syndrome (MDS)

['Geriatrics', 'Hematology', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 60s with a history of hypertension and hyperlipidemia presented to dermatology clinic with a 4-month history of fatigue, night sweats, and weight loss and 2 months of enlarging lesions on her scalp and hands. She reported no new medications or recent infection. Her temperature was 37.5 °C (99.5 °F); heart rate, 102/min; blood pressure, 98/72 mm Hg; respiratory rate, 12/min; and oxygen saturation, 94% on room air. Her skin examination revealed 3 tender, nonfluctuant 10-cm scalp plaques with overlying hemorrhagic crust and necrosis on an erythematous indurated base (Figure, left panel). Similar-appearing papules and plaques were present on the dorsal surfaces of her hands. The remainder of her physical examination was normal. ### OUTPUT:

JAMA_FINAL138

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 51-year-old woman presented with a 24-hour history of severe dizziness that she described as “room spinning,” right aural fullness, and a subjective right-sided hearing loss. She denied any medical history of vertigo, recent upper respiratory infection, head trauma, or prior otologic surgery. A physical examination revealed no abnormalities on otoscopic evaluation; however, a strongly positive right-sided Dix−Hallpike test was elicited with rotary nystagmus; a subsequent Epley maneuver was performed. The patient’s symptoms subjectively worsened during the following several days. Therefore, an audiogram test (Figure 1) and computed tomography (CT) of the temporal bone were performed. ### OUTPUT:

Pneumolabyrinth

['Vestibular Disorders', 'Otolaryngology', 'Otology', 'Audiology and Hearing']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 51-year-old man presented with a 24-hour history of severe dizziness that he described as “room spinning,” right aural fullness, and a subjective right-sided hearing loss. He denied any medical history of vertigo, recent upper respiratory infection, head trauma, or prior otologic surgery. A physical examination revealed no abnormalities on otoscopic evaluation; however, a strongly positive right-sided Dix−Hallpike test was elicited with rotary nystagmus; a subsequent Epley maneuver was performed. The patient’s symptoms subjectively worsened during the following several days. Therefore, an audiogram test (Figure 1) and computed tomography (CT) of the temporal bone were performed. ### OUTPUT:

JAMA_FINAL139

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 6-year-old boy with severe autism spectrum disorder (ASD) was brought to the hospital by his mother for whitening in the right eye. The patient was nonverbal at baseline and exhibited restrictive and repetitive behaviors. His diet consisted exclusively of cookies, apples, potato chips, and Gatorade. His mother noticed him frequently rubbing his eyes for several weeks, which she initially attributed to new-onset allergies. She did not describe any reduction in visual function or ability to perform low-luminance tasks. The patient was admitted and ophthalmology was consulted. He required an examination under sedation. His visual acuity could not be determined. There was no relative afferent pupillary defect in either eye. The eyelids were mildly erythematous with bilateral eyelash hypertrichosis. The conjunctiva and cornea appeared dry and leathery bilaterally. The right cornea was diffusely hazy with a 3-mm paracentral epithelial defect with 60% stromal thinning and a 1-mm infiltrate. There was a small crescentic fibrin deposit nasally in the right anterior chamber. The left cornea was diffusely hazy with a 1-mm epithelial defect without stromal thinning (Figure). Dilated examination showed bilateral grade 3 optic nerve head edema and otherwise normal retinal findings. Fortified vancomycin eye drops, 25 mg/mL, and tobramycin eye drops, 15 mg/mL, were initiated. Results of magnetic resonance imaging of the brain were normal. ### OUTPUT:

Xerophthalmia and keratomalacia from vitamin A deficiency

['Cornea', 'Nutrition', 'Ophthalmology', 'Psychiatry and Behavioral Health', 'Child and Adolescent Psychiatry']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 6-year-old girl with severe autism spectrum disorder (ASD) was brought to the hospital by her mother for whitening in the right eye. The patient was nonverbal at baseline and exhibited restrictive and repetitive behaviors. Her diet consisted exclusively of cookies, apples, potato chips, and Gatorade. Her mother noticed her frequently rubbing her eyes for several weeks, which she initially attributed to new-onset allergies. She did not describe any reduction in visual function or ability to perform low-luminance tasks. The patient was admitted and ophthalmology was consulted. She required an examination under sedation. Her visual acuity could not be determined. There was no relative afferent pupillary defect in either eye. The eyelids were mildly erythematous with bilateral eyelash hypertrichosis. The conjunctiva and cornea appeared dry and leathery bilaterally. The right cornea was diffusely hazy with a 3-mm paracentral epithelial defect with 60% stromal thinning and a 1-mm infiltrate. There was a small crescentic fibrin deposit nasally in the right anterior chamber. The left cornea was diffusely hazy with a 1-mm epithelial defect without stromal thinning (Figure). Dilated examination showed bilateral grade 3 optic nerve head edema and otherwise normal retinal findings. Fortified vancomycin eye drops, 25 mg/mL, and tobramycin eye drops, 15 mg/mL, were initiated. Results of magnetic resonance imaging of the brain were normal. ### OUTPUT:

JAMA_FINAL140

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 2-year-old girl who was otherwise healthy presented with a 10-month history of asymptomatic skin depressions in her neck, nape, and submandibular regions. The lesion initially occurred as an erythema in the neck and progressed centrifugally to the nape and submandibular areas. Atrophy was observed in the center of the lesion, surrounded by an erythematous border, with underlying blood vessels being visible deep to the atrophy (Figure, A). ### OUTPUT:

Lipodystrophia centrifugalis abdominalis infantilis

['Dermatology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 2-year-old boy who was otherwise healthy presented with a 10-month history of asymptomatic skin depressions in his neck, nape, and submandibular regions. The lesion initially occurred as an erythema in the neck and progressed centrifugally to the nape and submandibular areas. Atrophy was observed in the center of the lesion, surrounded by an erythematous border, with underlying blood vessels being visible deep to the atrophy (Figure, A). ### OUTPUT:

JAMA_FINAL141

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A healthy 27-year-old woman received a COVID-19 mRNA booster vaccine (Moderna) on December 7, 2021. She had not experienced adverse effects after the first 2 vaccine doses on January 17 and February 5, 2021. Twelve days after the booster vaccination, she developed pruritic wheals on her face and bilateral, transient eyelid swelling. Over the next week, a pruritic rash spread over her neck, chest, trunk, and arms; each lesion faded without scarring within 24 hours. She did not experience lip, tongue, or neck swelling; shortness of breath; wheezing; chest pain; or palpitations. Application of pressure to her forearm in a circular motion using a pen cap elicited wheal and flare lesions (Figure, left panel). On physical examination, performed 17 days after the onset of rash, her vital signs were normal. She had no tongue, lip, or throat swelling, and her lungs were clear to auscultation bilaterally. Wheal and flare lesions developed on her upper eyelids during the examination and resolved after approximately 30 minutes (Figure, right panel). Light pressure applied to her skin with a tongue depressor elicited wheal and flare lesions within 3 to 5 minutes. ### OUTPUT:

Inducible urticaria (symptomatic dermatographism) and acute urticaria

['Dermatology', 'Coronavirus (COVID-19)', 'Allergy and Clinical Immunology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A healthy 27-year-old man received a COVID-19 mRNA booster vaccine (Moderna) on December 7, 2021. He had not experienced adverse effects after the first 2 vaccine doses on January 17 and February 5, 2021. Twelve days after the booster vaccination, he developed pruritic wheals on his face and bilateral, transient eyelid swelling. Over the next week, a pruritic rash spread over his neck, chest, trunk, and arms; each lesion faded without scarring within 24 hours. He did not experience lip, tongue, or neck swelling; shortness of breath; wheezing; chest pain; or palpitations. Application of pressure to his forearm in a circular motion using a pen cap elicited wheal and flare lesions (Figure, left panel). On physical examination, performed 17 days after the onset of rash, his vital signs were normal. He had no tongue, lip, or throat swelling, and his lungs were clear to auscultation bilaterally. Wheal and flare lesions developed on his upper eyelids during the examination and resolved after approximately 30 minutes (Figure, right panel). Light pressure applied to his skin with a tongue depressor elicited wheal and flare lesions within 3 to 5 minutes. ### OUTPUT:

JAMA_FINAL142

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A middle-aged patient with a remote history of bilateral juvenile cataracts after posterior chamber intraocular lens (PCIOL) placement presented with decreased vision in the right eye for several months. There was no recent ocular trauma or intraocular surgery. At the time of the initial examination, visual acuity was 20/50 in the right eye and 20/20 in the left eye, with a refraction of −1.50 diopters (D) sphere in both eyes. Examination was notable for a superonasal area of pigmentation with elevation of the conjunctiva and an inferotemporally subluxed PCIOL in the right eye. Results of the fundus examination were reported to be normal in both eyes and the anterior examination of the left eye was notable for only a well-positioned PCIOL. The patient was referred to a cornea specialist for further evaluation and treatment. Because of the COVID-19 pandemic, specialty evaluation occurred 10 weeks later at which time the patient complained of progressive vision loss in the right eye. Visual acuity measured hand motion in the right eye with normal intraocular pressure. The PCIOL was subluxed inferotemporally with vitreous prolapse into the anterior chamber (Figure 1A). A 4 mm × 3.1-mm superonasal pigmented scleral lesion was also noted (Figure 1B). The examination of the left eye was remarkable only for a well-centered PCIOL and iris transillumination defects. ### OUTPUT:

Intraocular lens implant subluxation and extrascleral extension secondary to ciliochoroidal melanoma

['Cataract and Other Lens Disorders', 'Intraocular Tumors', 'Choroidal Disorders', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Intraocular lens implant subluxation and extrascleral extension secondary to ciliochoroidal melanoma. Case report: A middle-aged patient with a remote history of bilateral juvenile cataracts after posterior chamber intraocular lens (PCIOL) placement presented with decreased vision in the right eye for several months. There was no recent ocular trauma or intraocular surgery. At the time of the initial examination, visual acuity was 20/50 in the right eye and 20/20 in the left eye, with a refraction of −1.50 diopters (D) sphere in both eyes. Examination was notable for a superonasal area of pigmentation with elevation of the conjunctiva and an inferotemporally subluxed PCIOL in the right eye. Results of the fundus examination were reported to be normal in both eyes and the anterior examination of the left eye was notable for only a well-positioned PCIOL. The patient was referred to a cornea specialist for further evaluation and treatment. Because of the COVID-19 pandemic, specialty evaluation occurred 10 weeks later at which time the patient complained of progressive vision loss in the right eye. Visual acuity measured hand motion in the right eye with normal intraocular pressure. The PCIOL was subluxed inferotemporally with vitreous prolapse into the anterior chamber (Figure 1A). A 4 mm × 3.1-mm superonasal pigmented scleral lesion was also noted (Figure 1B). The examination of the left eye was remarkable only for a well-centered PCIOL and iris transillumination defects. ### OUTPUT:

JAMA_FINAL143

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old woman with a history of hypertension, type 2 diabetes, and chronic hepatitis B treated with tenofovir presented to the emergency department for evaluation of digital erythema and painful finger ulcers, which developed 6 months prior but which had increased in number and become more painful in the past several weeks. She also reported dyspnea on exertion, which developed 6 months prior to presentation. On physical examination, her peripheral oxygen saturation was 95% on room air. Auscultation of her lungs revealed crackles at the bases bilaterally. She had normal strength throughout all muscle groups and full range of motion in the joints of her hands. The palmar surfaces of her hands revealed livedo racemosa, erythema, and retiform purpura; ulcers overlying her phalangeal joint creases and fingertips; and scale and fissures on several digits (Figure). On the dorsal surfaces there was a large ulcer on the right second metacarpophalangeal joint and erythematous papules over several metacarpophalangeal joints. Ulcers were also noted on her elbows. Laboratory testing showed a hemoglobin level of 10.5 g/dL and normal creatine kinase level. The patient was admitted to the hospital for pain management and expedited workup of her progressive finger ulcerations. ### OUTPUT:

Anti–melanoma differentiation–associated protein 5 (MDA5) antibody-positive dermatomyositis

['Pulmonary Medicine', 'Rheumatology', 'Connective Tissue Disease of the Skin', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old man with a history of hypertension, type 2 diabetes, and chronic hepatitis B treated with tenofovir presented to the emergency department for evaluation of digital erythema and painful finger ulcers, which developed 6 months prior but which had increased in number and become more painful in the past several weeks. He also reported dyspnea on exertion, which developed 6 months prior to presentation. On physical examination, his peripheral oxygen saturation was 95% on room air. Auscultation of his lungs revealed crackles at the bases bilaterally. He had normal strength throughout all muscle groups and full range of motion in the joints of his hands. The palmar surfaces of his hands revealed livedo racemosa, erythema, and retiform purpura; ulcers overlying his phalangeal joint creases and fingertips; and scale and fissures on several digits (Figure). On the dorsal surfaces there was a large ulcer on the right second metacarpophalangeal joint and erythematous papules over several metacarpophalangeal joints. Ulcers were also noted on his elbows. Laboratory testing showed a hemoglobin level of 10.5 g/dL and normal creatine kinase level. The patient was admitted to the hospital for pain management and expedited workup of his progressive finger ulcerations. ### OUTPUT:

JAMA_FINAL144

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old man presented with a history of previous left superficial parotidectomy 10 years before for a Warthin tumor. His histology results showed a 5-cm Warthin tumor, with a focus of nodular oncocytic hyperplasia in the adjacent parenchyma and reactive intraparotid lymph nodes. He presented to the ear, nose, and throat clinic and complained of pain in the operative site of 6 months duration. This occurred intermittently once a week and lasted for a few minutes each time. It was associated with a small lump over the left neck, and the pain was worse on touch and head turning. On examination, there was a 3-mm nodularity palpated deep to the neck wound along the mid sternocleidomastoid muscle. It was associated with focal tenderness. His facial nerve function was otherwise normal, and sensation in the ear lobe was intact. A magnetic resonance imaging (MRI) scan was performed, and the results showed no focal lesion in either parotid glands or at the area of interest over the left sternocleidomastoid muscle. The patient was counseled for an excisional biopsy of the left neck nodule. The intraoperative photograph of the neck and the excised specimen is shown in Figure 1. ### OUTPUT:

Greater auricular nerve neuroma

['Otolaryngology', 'Head and Neck Surgery', 'Pain Medicine', 'Neurology', 'Neuromuscular Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old woman presented with a history of previous left superficial parotidectomy 10 years before for a Warthin tumor. Her histology results showed a 5-cm Warthin tumor, with a focus of nodular oncocytic hyperplasia in the adjacent parenchyma and reactive intraparotid lymph nodes. She presented to the ear, nose, and throat clinic and complained of pain in the operative site of 6 months duration. This occurred intermittently once a week and lasted for a few minutes each time. It was associated with a small lump over the left neck, and the pain was worse on touch and head turning. On examination, there was a 3-mm nodularity palpated deep to the neck wound along the mid sternocleidomastoid muscle. It was associated with focal tenderness. Her facial nerve function was otherwise normal, and sensation in the ear lobe was intact. A magnetic resonance imaging (MRI) scan was performed, and the results showed no focal lesion in either parotid glands or at the area of interest over the left sternocleidomastoid muscle. The patient was counseled for an excisional biopsy of the left neck nodule. The intraoperative photograph of the neck and the excised specimen is shown in Figure 1. ### OUTPUT:

JAMA_FINAL145

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 60s with a history of hyperlipidemia, hypothyroidism, and chronic migraines presented with 9 months of progressively worsening left-sided ptosis, which was more notable at night and with fatigue. She denied experiencing pain, diplopia, muscle weakness, dysarthria, dysphagia, difficulty breathing, or other neurologic deficits. On examination, corrected visual acuity was 20/20 bilaterally, with normal color vision, visual fields, intraocular pressure, extraocular movements, alignment, and pupils. External examination was notable for left upper eyelid ptosis (Figure 1), with a margin-to-reflex distance 1 of 3.5 mm on the right and 0.5 mm on the left, intact levator function, and no fatiguability on sustained upgaze. There was no evidence of eyelid edema, erythema, or tenderness to palpation. There were no palpable adnexal masses or orbital rim deformities, but there was mild fullness in the left superior sulcus and mildly increased left-sided resistance to retropulsion. However, Hertel exophthalmometry did not reveal any relative proptosis. No lacrimal gland abnormalities or conjunctival masses were seen with upper eyelid eversion. There was no palpable preauricular or cervical lymphadenopathy. Slitlamp and fundus examination findings were normal. Serological testing results for antiacetylcholine receptor antibody were negative. ### OUTPUT:

Unilateral ptosis secondary to mantle cell lymphoma of the left lacrimal gland

['External Eye Disease', 'Neuro-ophthalmology', 'Oncology', 'Ophthalmology', 'Lymphomas']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 60s with a history of hyperlipidemia, hypothyroidism, and chronic migraines presented with 9 months of progressively worsening left-sided ptosis, which was more notable at night and with fatigue. He denied experiencing pain, diplopia, muscle weakness, dysarthria, dysphagia, difficulty breathing, or other neurologic deficits. On examination, corrected visual acuity was 20/20 bilaterally, with normal color vision, visual fields, intraocular pressure, extraocular movements, alignment, and pupils. External examination was notable for left upper eyelid ptosis (Figure 1), with a margin-to-reflex distance 1 of 3.5 mm on the right and 0.5 mm on the left, intact levator function, and no fatiguability on sustained upgaze. There was no evidence of eyelid edema, erythema, or tenderness to palpation. There were no palpable adnexal masses or orbital rim deformities, but there was mild fullness in the left superior sulcus and mildly increased left-sided resistance to retropulsion. However, Hertel exophthalmometry did not reveal any relative proptosis. No lacrimal gland abnormalities or conjunctival masses were seen with upper eyelid eversion. There was no palpable preauricular or cervical lymphadenopathy. Slitlamp and fundus examination findings were normal. Serological testing results for antiacetylcholine receptor antibody were negative. ### OUTPUT:

JAMA_FINAL146

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy man in his 20s presented to the dermatology department with thickening and swelling of hands after immersion in water, accompanied by burning pruritus for 3 years. The lesions occurred as symmetrical white and transparent papules, white keratosis, excessive wrinkling on the dorsum of hands after water immersion and worsened in summer, and remitted in winter. He was treated with topical tretinoin ointment intermittently per a diagnosis of chronic eczema at the local clinic with little improvement. The lesions gradually aggravated, and the affected area dispersed to wrists and elbows during past the 1.5 years. He attributed these changes to the need for washing hands frequently in the period of the COVID-19 epidemic. He had no family history of similar skin problems and did not have a history of hyperhidrosis, cystic fibrosis, atopy, or trauma to the hands. Physical examination showed some changes emerged on both hands after water immersion contrasting with any other condition (Figure, A and B). We took a skin biopsy specimen from white papules on the right hand, and representative histopathologic features are shown in the Figure, C and D. ### OUTPUT:

Aquagenic syringeal acrokeratoderma

['Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy woman in her 20s presented to the dermatology department with thickening and swelling of hands after immersion in water, accompanied by burning pruritus for 3 years. The lesions occurred as symmetrical white and transparent papules, white keratosis, excessive wrinkling on the dorsum of hands after water immersion and worsened in summer, and remitted in winter. She was treated with topical tretinoin ointment intermittently per a diagnosis of chronic eczema at the local clinic with little improvement. The lesions gradually aggravated, and the affected area dispersed to wrists and elbows during the past 1.5 years. She attributed these changes to the need for washing hands frequently in the period of the COVID-19 epidemic. She had no family history of similar skin problems and did not have a history of hyperhidrosis, cystic fibrosis, atopy, or trauma to the hands. Physical examination showed some changes emerged on both hands after water immersion contrasting with any other condition (Figure, A and B). We took a skin biopsy specimen from white papules on the right hand, and representative histopathologic features are shown in the Figure, C and D. ### OUTPUT:

JAMA_FINAL147

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: On the day of giving birth via a normal vaginal delivery, a healthy woman in her 20s developed painful swelling on her right thigh, at the site of a methergine injection administered 1 day prior. Despite 3 days of treatment with an oral antibiotic (cefalexin), her thigh pain and swelling did not improve, and she was readmitted to the hospital and intravenous clindamycin was started. Wound cultures and blood cultures obtained during incision and drainage performed on hospital day 1 were negative for bacterial, mycobacterial, and fungal organisms. The following day, her temperature was 39.4 °C (102.9 °F), blood pressure was 86/42 mm Hg, and heart rate was 131/min. She was transferred to the intensive care unit for presumed septic shock, and her antibiotics were changed to vancomycin and meropenem. Surgical debridement of the right thigh was performed on hospital day 3. On hospital day 4, a new purple dusky border developed along the wound edge, and the patent underwent a second surgical debridement. After debridement on hospital day 5, her temperature was 39.8 °C (103.6 °F), and she required vasopressor infusion with norepinephrine for shock. Her right thigh had a deep 9 × 8–cm ulcer with a dusky violaceous border extending 2 to 5 cm from the wound edge (Figure, left), with many 1- to 2-mm pustules (not visible in Figure). Laboratory testing showed a white blood cell count of 30 000/μL (88% neutrophils); lactate level, 77.5 mg/dL (8.6 mmol/L); and procalcitonin level, 16.1 ng/mL (reference, <0.1 ng/mL). Histologic examination of the tissue obtained during the second surgical debridement revealed ulceration with extensive neutrophilic inflammation (Figure, right). Stains for microorganisms, and tissue and blood cultures, remained negative. ### OUTPUT:

Necrotizing pyoderma gangrenosum

['Dermatology', 'Surgery', 'Pathology and Laboratory Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: On the day of giving birth via a normal vaginal delivery, a healthy man in his 20s developed painful swelling on his right thigh, at the site of a methergine injection administered 1 day prior. Despite 3 days of treatment with an oral antibiotic (cefalexin), his thigh pain and swelling did not improve, and he was readmitted to the hospital and intravenous clindamycin was started. Wound cultures and blood cultures obtained during incision and drainage performed on hospital day 1 were negative for bacterial, mycobacterial, and fungal organisms. The following day, his temperature was 39.4 °C (102.9 °F), blood pressure was 86/42 mm Hg, and heart rate was 131/min. He was transferred to the intensive care unit for presumed septic shock, and his antibiotics were changed to vancomycin and meropenem. Surgical debridement of the right thigh was performed on hospital day 3. On hospital day 4, a new purple dusky border developed along the wound edge, and the patient underwent a second surgical debridement. After debridement on hospital day 5, his temperature was 39.8 °C (103.6 °F), and he required vasopressor infusion with norepinephrine for shock. His right thigh had a deep 9 × 8–cm ulcer with a dusky violaceous border extending 2 to 5 cm from the wound edge (Figure, left), with many 1- to 2-mm pustules (not visible in Figure). Laboratory testing showed a white blood cell count of 30 000/μL (88% neutrophils); lactate level, 77.5 mg/dL (8.6 mmol/L); and procalcitonin level, 16.1 ng/mL (reference, <0.1 ng/mL). Histologic examination of the tissue obtained during the second surgical debridement revealed ulceration with extensive neutrophilic inflammation (Figure, right). Stains for microorganisms, and tissue and blood cultures, remained negative. ### OUTPUT:

JAMA_FINAL148

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old woman with osteoarthritis and obstructive sleep apnea treated with nasal continuous positive airway pressure (CPAP) presented with several months of worsening pain in her hands (first metacarpophalangeal joints), wrists, and feet. Radiographs of the hands and wrists performed 1 month prior showed degenerative changes but no bone erosions. Her vital signs and physical examination findings were normal. She had no redness, warmth, or swelling of any joints, and her skin examination was unremarkable. However, a deformity of the nasal bridge was noted after she was asked to remove her face mask, which she was wearing as required during the COVID-19 pandemic (Figure). She reported no history of facial trauma, recent travel, illicit drug use, or high-risk sexual behavior. The nasal deformity, which she attributed to use of her CPAP mask, had developed gradually over the past several years. ### OUTPUT:

Granulomatosis with polyangiitis (GPA) with rapidly progressive pauci-immune glomerulonephritis (RPGN)

['Nephrology', 'Rheumatology', 'Pulmonary Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old man with osteoarthritis and obstructive sleep apnea treated with nasal continuous positive airway pressure (CPAP) presented with several months of worsening pain in his hands (first metacarpophalangeal joints), wrists, and feet. Radiographs of the hands and wrists performed 1 month prior showed degenerative changes but no bone erosions. His vital signs and physical examination findings were normal. He had no redness, warmth, or swelling of any joints, and his skin examination was unremarkable. However, a deformity of the nasal bridge was noted after he was asked to remove his face mask, which he was wearing as required during the COVID-19 pandemic (Figure). He reported no history of facial trauma, recent travel, illicit drug use, or high-risk sexual behavior. The nasal deformity, which he attributed to use of his CPAP mask, had developed gradually over the past several years. ### OUTPUT:

JAMA_FINAL149

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old woman was referred with a 6-week history of blurry vision, ocular pain, and subconjunctival yellow discoloration in the left eye. Suspicious retinal detachment and intraocular mass were identified, which raised concerns for choroidal melanoma. No symptoms or signs were reported in the right eye. Her ocular history included bilateral cataract surgery 5 years prior. Review of systems yielded negative results, including for ocular trauma, jaundice, and cutaneous melanoma. She had no history of tobacco use. On examination of the left eye, visual acuity was hand motion, and intraocular pressure was 8 mm Hg. The anterior segment showed diffuse conjunctival chemosis of yellow hue, low-grade aqueous reaction, and pseudophakia (Figure 1A). On the fundus evaluation, large pockets of subretinal fluid suggested choroidal effusion based on marked fluid shifting with head position. B-scan ultrasonography confirmed 4-quadrant choroidal hemorrhage and partially mobile serous retinal detachment. B-scans also exhibited a solid lesion from the 6- to 10-o’clock meridians with irregular shape and variable internal reflectivity, measuring 5.8 mm in height. Magnetic resonance imaging was requested to delineate the mass from the surrounding clot (Figure 1B). In the interim, she received oral steroids aiming to contain the abundant exudation and topical atropine for pain, evolving with minimal clinical improvement on these features. ### OUTPUT:

Choroidal metastasis from lung adenocarcinoma

['Oncology', 'Ophthalmology', 'Lung Cancer', 'Choroidal Disorders', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old man was referred with a 6-week history of blurry vision, ocular pain, and subconjunctival yellow discoloration in the left eye. Suspicious retinal detachment and intraocular mass were identified, which raised concerns for choroidal melanoma. No symptoms or signs were reported in the right eye. His ocular history included bilateral cataract surgery 5 years prior. Review of systems yielded negative results, including for ocular trauma, jaundice, and cutaneous melanoma. He had no history of tobacco use. On examination of the left eye, visual acuity was hand motion, and intraocular pressure was 8 mm Hg. The anterior segment showed diffuse conjunctival chemosis of yellow hue, low-grade aqueous reaction, and pseudophakia (Figure 1A). On the fundus evaluation, large pockets of subretinal fluid suggested choroidal effusion based on marked fluid shifting with head position. B-scan ultrasonography confirmed 4-quadrant choroidal hemorrhage and partially mobile serous retinal detachment. B-scans also exhibited a solid lesion from the 6- to 10-o’clock meridians with irregular shape and variable internal reflectivity, measuring 5.8 mm in height. Magnetic resonance imaging was requested to delineate the mass from the surrounding clot (Figure 1B). In the interim, he received oral steroids aiming to contain the abundant exudation and topical atropine for pain, evolving with minimal clinical improvement on these features. ### OUTPUT:

JAMA_FINAL150

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 60s with a medical history of hypertension was referred for new-onset fluctuating diplopia and worsening right upper eyelid ptosis. The patient underwent right-sided ptosis repair at another hospital less than 1 year earlier without improvement. Best-corrected visual acuity was 20/30 OU, and pupil examination revealed no anisocoria or afferent pupillary defect. Color vision was full in both eyes. External examination revealed a margin reflex distance 1 (MRD1) of 0 mm OD, 4 mm OS without fatigability in extended upgaze (Figure 1A). The patient had a small exotropia in primary gaze with a −2 supraduction deficit. No proptosis was observed. An ice pack was applied in the clinic to the ptotic eyelid for 2 minutes, which led to a 1.5-mm improvement (Figure 1B) in ptosis and no appreciable change in strabismus. The patient reported no associated headache, weakness, or difficulty swallowing. ### OUTPUT:

Superior divisional oculomotor nerve palsy due to internal carotid artery aneurysm

['Neuro-ophthalmology', 'Ophthalmology', 'Carotid and Intracranial Artery Disease']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 60s with a medical history of hypertension was referred for new-onset fluctuating diplopia and worsening right upper eyelid ptosis. The patient underwent right-sided ptosis repair at another hospital less than 1 year earlier without improvement. Best-corrected visual acuity was 20/30 OU, and pupil examination revealed no anisocoria or afferent pupillary defect. Color vision was full in both eyes. External examination revealed a margin reflex distance 1 (MRD1) of 0 mm OD, 4 mm OS without fatigability in extended upgaze (Figure 1A). The patient had a small exotropia in primary gaze with a −2 supraduction deficit. No proptosis was observed. An ice pack was applied in the clinic to the ptotic eyelid for 2 minutes, which led to a 1.5-mm improvement (Figure 1B) in ptosis and no appreciable change in strabismus. The patient reported no associated headache, weakness, or difficulty swallowing. ### OUTPUT:

JAMA_FINAL151

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A teenaged boy presented to the outpatient clinic with a 1-year history of asymptomatic cutaneous lesions on the face that had progressively spread to the trunk and extremities. He also had asthenia and mild intermittent arthralgias. Physical examination revealed multiple millimetric erythematous to hyperpigmented monomorphic keratotic papules involving the head, trunk, and extremities. Symmetric annular brown erythematous plaques on the cheeks and temples were also seen. There were no vesicles or pustules (Figure, A and B). Laboratory investigations revealed a normal white blood cell count, mild anemia (hemoglobin level, 11.3 g/dL; normal level 12.50-15.50 g/dL; to convert to g/L, multiply by 10.0), hypocomplementemia, and moderate proteinuria. Autoimmune serology results showed raised levels of antinuclear antibodies (>1:160), anti-Smith antibodies, SSA/Ro antibodies, SSB/La antibodies, and anti-U1RNP antibodies. Anti-dsDNA antibodies, lupus anticoagulant, rheumatoid factor, IgG and IgM anticardiolipin antibody, and anti-β2 glycoprotein 1 antibody results were negative. A biopsy specimen obtained from an erythematous papule on the trunk and stained with hematoxylin-eosin is shown in the Figure, C and D. ### OUTPUT:

Nonbullous neutrophilic lupus erythematosus

['Dermatology', 'Connective Tissue Disease of the Skin', 'Pediatrics', 'Adolescent Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A teenaged girl presented to the outpatient clinic with a 1-year history of asymptomatic cutaneous lesions on the face that had progressively spread to the trunk and extremities. She also had asthenia and mild intermittent arthralgias. Physical examination revealed multiple millimetric erythematous to hyperpigmented monomorphic keratotic papules involving the head, trunk, and extremities. Symmetric annular brown erythematous plaques on the cheeks and temples were also seen. There were no vesicles or pustules (Figure, A and B). Laboratory investigations revealed a normal white blood cell count, mild anemia (hemoglobin level, 11.3 g/dL; normal level 12.50-15.50 g/dL; to convert to g/L, multiply by 10.0), hypocomplementemia, and moderate proteinuria. Autoimmune serology results showed raised levels of antinuclear antibodies (>1:160), anti-Smith antibodies, SSA/Ro antibodies, SSB/La antibodies, and anti-U1RNP antibodies. Anti-dsDNA antibodies, lupus anticoagulant, rheumatoid factor, IgG and IgM anticardiolipin antibody, and anti-β2 glycoprotein 1 antibody results were negative. A biopsy specimen obtained from an erythematous papule on the trunk and stained with hematoxylin-eosin is shown in the Figure, C and D. ### OUTPUT:

JAMA_FINAL152

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 20-year-old woman presented with complaints of blurred vision in her left eye over several weeks and a growing, bulging left-eye mass. Her history was notable for bilateral colobomas involving the iris, optic nerve, and retina; congenital cataracts after lensectomy of the left eye; retinal detachment with proliferative vitreoretinopathy of the left eye requiring a scleral buckle and silicone oil; and intractable glaucoma in the left eye requiring a superior trabeculectomy, an inferotemporal Ahmed tube implant, and multiple diode cyclophotocoagulation treatments. Because of the high risk of retinal redetachment, the silicone oil was retained throughout the glaucoma procedures. The patient presented 9 months after the last cyclophotocoagulation procedure. At presentation, she was taking dorzolamide-timolol, brimonidine, netarsudil, and latanoprost for her left eye. Best-corrected visual acuity was 20/80 OD and light perception OS. Intraocular pressures (IOPs) were 11 mm Hg OD and 20 mm Hg OS. Examination of the left eye revealed a large, firm, pink subconjunctival mass inferotemporally near the Ahmed valve (Figure 1). There was a left hypertropia of more than 45° by Hirschberg test. The anterior chamber was deep with fine silicone oil bubbles superiorly. The aphakic left eye revealed a well-positioned tube. Cup-disc ratios were 0.7 OD and 0.8 OS. The retina was centrally attached under silicone oil with a stable peripheral tractional retinal detachment. ### OUTPUT:

Subconjunctival silicone oil granuloma

['Ophthalmology', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 20-year-old man presented with complaints of blurred vision in his left eye over several weeks and a growing, bulging left-eye mass. His history was notable for bilateral colobomas involving the iris, optic nerve, and retina; congenital cataracts after lensectomy of the left eye; retinal detachment with proliferative vitreoretinopathy of the left eye requiring a scleral buckle and silicone oil; and intractable glaucoma in the left eye requiring a superior trabeculectomy, an inferotemporal Ahmed tube implant, and multiple diode cyclophotocoagulation treatments. Because of the high risk of retinal redetachment, the silicone oil was retained throughout the glaucoma procedures. The patient presented 9 months after the last cyclophotocoagulation procedure. At presentation, he was taking dorzolamide-timolol, brimonidine, netarsudil, and latanoprost for his left eye. Best-corrected visual acuity was 20/80 OD and light perception OS. Intraocular pressures (IOPs) were 11 mm Hg OD and 20 mm Hg OS. Examination of the left eye revealed a large, firm, pink subconjunctival mass inferotemporally near the Ahmed valve (Figure 1). There was a left hypertropia of more than 45° by Hirschberg test. The anterior chamber was deep with fine silicone oil bubbles superiorly. The aphakic left eye revealed a well-positioned tube. Cup-disc ratios were 0.7 OD and 0.8 OS. The retina was centrally attached under silicone oil with a stable peripheral tractional retinal detachment. ### OUTPUT:

JAMA_FINAL153

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her mid-20s presented with cardiogenic shock. On presentation, she was afebrile with cool extremities; her blood pressure was 75/51 mm Hg, heart rate was 147 beats per minute, respiratory rate was 20 breaths per minute, and oxygen saturation was 99% on mechanical ventilation. Her chest examination revealed bilateral coarse breath sounds and distant heart sounds. Transthoracic echocardiogram revealed an ejection fraction of 10% with elevated filling pressures and no significant valvular abnormalities. Owing to hemodynamic instability, the patient was given venoarterial extracorporeal membrane oxygenation (ECMO) with the peripheral ventricular assist device (pVAD) Impella CP (Abiomed) and was administered high-dose intravenous corticosteroids. Endomyocardial biopsy showed lymphocytic viral myocarditis. There was significant hemodynamic improvement within 48 hours; transthoracic echocardiogram was obtained and showed impressive recovery of the left ventricular function to an ejection fraction of 45%. As a result, ECMO was decannulated after 72 hours. Left pVAD support was maintained alone for another 24 hours. In the interim, her vitals remained unchanged, but the patient developed hematuria and laboratory parameters suggestive of hemolysis. Chest radiography showed pulmonary edema, and low-flow alarms sounded on the device console. Transthoracic echocardiogram showed severe mitral regurgitation (MR), and a transesophageal echocardiogram was performed to evaluate pVAD positioning (Figure and Video). ### OUTPUT:

Iatrogenic mitral regurgitation

['Urology', 'Cardiology', 'Medical Devices and Equipment', 'Nephrology', 'Acute Coronary Syndromes']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his mid-20s presented with cardiogenic shock. On presentation, he was afebrile with cool extremities; his blood pressure was 75/51 mm Hg, heart rate was 147 beats per minute, respiratory rate was 20 breaths per minute, and oxygen saturation was 99% on mechanical ventilation. His chest examination revealed bilateral coarse breath sounds and distant heart sounds. Transthoracic echocardiogram revealed an ejection fraction of 10% with elevated filling pressures and no significant valvular abnormalities. Owing to hemodynamic instability, the patient was given venoarterial extracorporeal membrane oxygenation (ECMO) with the peripheral ventricular assist device (pVAD) Impella CP (Abiomed) and was administered high-dose intravenous corticosteroids. Endomyocardial biopsy showed lymphocytic viral myocarditis. There was significant hemodynamic improvement within 48 hours; transthoracic echocardiogram was obtained and showed impressive recovery of the left ventricular function to an ejection fraction of 45%. As a result, ECMO was decannulated after 72 hours. Left pVAD support was maintained alone for another 24 hours. In the interim, his vitals remained unchanged, but the patient developed hematuria and laboratory parameters suggestive of hemolysis. Chest radiography showed pulmonary edema, and low-flow alarms sounded on the device console. Transthoracic echocardiogram showed severe mitral regurgitation (MR), and a transesophageal echocardiogram was performed to evaluate pVAD positioning (Figure and Video). ### OUTPUT:

JAMA_FINAL154

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A white man in his early 80s with history of autoimmune pancreatitis, recurrent colon polyps, and benign prostatic hyperplasia developed rapid, painless vision loss of both eyes over a 2-week period 6 months after cataract surgery. Vision was 20/250 OD and 20/60 OS. The anterior segment was unremarkable in either eye, while the posterior segment examination noted 1+ vitreous cell, asteroid hyalosis, and a multilobulated, serous retinal detachment (RD) in the right eye and trace vitreous cell and a multilobulated, serous RD in the left eye. Imaging included B-scan, optical coherence tomography, and fundus autofluorescence, which revealed diffuse choroidal and ciliary body thickening, multifocal pockets of subretinal fluid, and speckled hyperautofluorescence and hypoautofluorescence in both eyes (Figure 1). No poliosis or skin changes were noted. A review of systems was unremarkable, most notably a lack of any pulmonary symptoms. A focused laboratory evaluation identified a significantly elevated angiotensin-converting enzyme (ACE) level and antinuclear antibody titer, but serum lysozyme, syphilis, and tuberculosis testing had negative results. To better differentiate between Vogt-Koyanagi-Harada (VKH) syndrome, a lymphoproliferative disorder, or sarcoidosis as the underlying cause of the vitreous inflammation and multilobulated, serous RD in both eyes, a computed tomographic scan was performed. It showed marked lymphadenopathy throughout the mediastinum and diffuse scleral thickening in both eyes. The institute’s radiologists believed these computed tomography findings were nonspecific and could be indicative of either sarcoidosis or intraocular lymphoma. ### OUTPUT:

Biopsy-proven, Harada-like ocular sarcoidosis in both eyes

['Ophthalmology', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A white woman in her early 80s with history of autoimmune pancreatitis, recurrent colon polyps, and benign prostatic hyperplasia developed rapid, painless vision loss of both eyes over a 2-week period 6 months after cataract surgery. Vision was 20/250 OD and 20/60 OS. The anterior segment was unremarkable in either eye, while the posterior segment examination noted 1+ vitreous cell, asteroid hyalosis, and a multilobulated, serous retinal detachment (RD) in the right eye and trace vitreous cell and a multilobulated, serous RD in the left eye. Imaging included B-scan, optical coherence tomography, and fundus autofluorescence, which revealed diffuse choroidal and ciliary body thickening, multifocal pockets of subretinal fluid, and speckled hyperautofluorescence and hypoautofluorescence in both eyes (Figure 1). No poliosis or skin changes were noted. A review of systems was unremarkable, most notably a lack of any pulmonary symptoms. A focused laboratory evaluation identified a significantly elevated angiotensin-converting enzyme (ACE) level and antinuclear antibody titer, but serum lysozyme, syphilis, and tuberculosis testing had negative results. To better differentiate between Vogt-Koyanagi-Harada (VKH) syndrome, a lymphoproliferative disorder, or sarcoidosis as the underlying cause of the vitreous inflammation and multilobulated, serous RD in both eyes, a computed tomographic scan was performed. It showed marked lymphadenopathy throughout the mediastinum and diffuse scleral thickening in both eyes. The institute’s radiologists believed these computed tomography findings were nonspecific and could be indicative of either sarcoidosis or intraocular lymphoma. ### OUTPUT:

JAMA_FINAL155

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 50s presented with asymptomatic keratotic papules, first noticed on the left middle and ring fingers and left toe web spaces more than 10 years earlier. The papules progressed proximally over the subsequent decade to involve the forearm, arm, scapular area, ankle, shin, and thigh, but only affected the left side of the body. The patient’s face, palms, soles, and entire right side of the body were spared. The patient has a history of rosacea being treated with topical metronidazole gel for flares but was otherwise asymptomatic. The patient did not have any alopecia, night blindness, or dry eyes or skin. There was no history of any exposure to radiation or arsenic, nutritional deficiency, inflammatory skin disease, or malignant neoplasm. There was no family history of a similar condition. Examination revealed multiple, submillimeter, skin-colored to yellowish keratotic spiny projections over the aforementioned areas, only on the left side of the body (Figure, A and B). Punch biopsy from a lesion showed orthokeratosis with parakeratotic columns emerging from an epidermal invagination. The epidermis was mildly acanthotic and with a normal granular layer. There was a sparse superficial perivascular lymphocytic infiltrate. Adjacent hair follicles were unaffected (Figure, C). ### OUTPUT:

Multiple minute digitate hyperkeratosis

['Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 50s presented with asymptomatic keratotic papules, first noticed on the left middle and ring fingers and left toe web spaces more than 10 years earlier. The papules progressed proximally over the subsequent decade to involve the forearm, arm, scapular area, ankle, shin, and thigh, but only affected the left side of the body. The patient’s face, palms, soles, and entire right side of the body were spared. The patient has a history of rosacea being treated with topical metronidazole gel for flares but was otherwise asymptomatic. The patient did not have any alopecia, night blindness, or dry eyes or skin. There was no history of any exposure to radiation or arsenic, nutritional deficiency, inflammatory skin disease, or malignant neoplasm. There was no family history of a similar condition. Examination revealed multiple, submillimeter, skin-colored to yellowish keratotic spiny projections over the aforementioned areas, only on the left side of the body (Figure, A and B). Punch biopsy from a lesion showed orthokeratosis with parakeratotic columns emerging from an epidermal invagination. The epidermis was mildly acanthotic and with a normal granular layer. There was a sparse superficial perivascular lymphocytic infiltrate. Adjacent hair follicles were unaffected (Figure, C). ### OUTPUT:

JAMA_FINAL156

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A White woman in her 40s was referred to an outside ophthalmologist after developing nausea and a headache following a dilated eye examination. She was found to have narrow angles in both eyes and a laser peripheral iridotomy (LPI) was performed in her left eye. Two weeks later she developed flickering photopsias and a temporal scotoma progressing to a “brown tint” of her vision in her left eye. Her vision had decreased in her left eye and macular and optic nerve edema were noted and she was subsequently referred to us. In our clinic, her visual acuity was 20/20 OD and 20/50 OS, and she had normal intraocular pressure, a shallow anterior chamber but open angle in both eyes, a patent LPI in the left eye, and clear crystalline lenses in both eyes. The rest of her anterior segment was unremarkable. The posterior examination was notable for shifting subretinal fluid with choroidal detachments without retinal breaks, inflammation, or optic nerve edema and leopard spotting, while her right eye was unremarkable (Figure, A). Fluorescein angiography was unrevealing, while optical coherence tomography showed shallow subretinal fluid and an irregular and thickened choroid (Figure, B). Ultrasonography showed an axial length of 20.0 mm, thickened sclera, anteriorly rotated ciliary body, and 360° of ciliochoroidal detachments in both eyes but worse in the left eye. Results of a systemic laboratory evaluation for infectious and noninfectious disorders were unremarkable. Systemic corticosteroids failed to resolve the subretinal fluid and her vision declined. ### OUTPUT:

Uveal effusion syndrome

['Glaucoma', 'Ophthalmology', 'Choroidal Disorders', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A White man in his 40s was referred to an outside ophthalmologist after developing nausea and a headache following a dilated eye examination. He was found to have narrow angles in both eyes and a laser peripheral iridotomy (LPI) was performed in his left eye. Two weeks later he developed flickering photopsias and a temporal scotoma progressing to a “brown tint” of his vision in his left eye. His vision had decreased in his left eye and macular and optic nerve edema were noted and he was subsequently referred to us. In our clinic, his visual acuity was 20/20 OD and 20/50 OS, and he had normal intraocular pressure, a shallow anterior chamber but open angle in both eyes, a patent LPI in the left eye, and clear crystalline lenses in both eyes. The rest of his anterior segment was unremarkable. The posterior examination was notable for shifting subretinal fluid with choroidal detachments without retinal breaks, inflammation, or optic nerve edema and leopard spotting, while his right eye was unremarkable (Figure, A). Fluorescein angiography was unrevealing, while optical coherence tomography showed shallow subretinal fluid and an irregular and thickened choroid (Figure, B). Ultrasonography showed an axial length of 20.0 mm, thickened sclera, anteriorly rotated ciliary body, and 360° of ciliochoroidal detachments in both eyes but worse in the left eye. Results of a systemic laboratory evaluation for infectious and noninfectious disorders were unremarkable. Systemic corticosteroids failed to resolve the subretinal fluid and his vision declined. ### OUTPUT:

JAMA_FINAL157

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man aged 57 years presented to the emergency department after 3 weeks of bilateral periorbital pain and swelling with associated headaches. He reported diplopia and pain with extraocular movement. There were no constitutional, dermatologic, or neurologic symptoms. The patient endorsed a history of Crohn disease, and his medication had been changed from infliximab to ustekinumab 6 weeks prior owing to persistent intestinal inflammation. Clinical examination revealed bilateral periorbital edema, diplopia with decreased abduction in the right eye and decreased adduction in the left eye, chemosis, proptosis, and conjunctival hyperemia (Figure 1A). Visual acuity and neurologic and fundus examination findings were otherwise normal with no sign of optic neuropathy. ### OUTPUT:

Medication-induced orbital myositis secondary to ustekinumab

['Clinical Pharmacy and Pharmacology', 'Gastroenterology', 'Inflammatory Bowel Disease', 'Adverse Drug Events', 'Gastroenterology and Hepatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Medication-induced orbital myositis secondary to ustekinumab. Case report: A woman aged 57 years presented to the emergency department after 3 weeks of bilateral periorbital pain and swelling with associated headaches. She reported diplopia and pain with extraocular movement. There were no constitutional, dermatologic, or neurologic symptoms. The patient endorsed a history of Crohn disease, and her medication had been changed from infliximab to ustekinumab 6 weeks prior owing to persistent intestinal inflammation. Clinical examination revealed bilateral periorbital edema, diplopia with decreased abduction in the right eye and decreased adduction in the left eye, chemosis, proptosis, and conjunctival hyperemia (Figure 1A). Visual acuity and neurologic and fundus examination findings were otherwise normal with no sign of optic neuropathy. ### OUTPUT:

JAMA_FINAL158

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 40s with a medical history of multiple sclerosis consulted for the sudden development of 2 adjacent nodules on the left arm. An excision with 1-cm margins of the left arm demonstrated desmoplastic melanoma with a Breslow thickness of 1 mm, and a left axillary sentinel lymph node biopsy (SLNB) had been performed 3 weeks before under general anesthesia. The patient was also being treated with subcutaneous interferon beta 1a for the multiple sclerosis. Physical examination revealed 2 indurated and mobile subcutaneous nodules on the anterior surface of the arm 5 cm distal to the surgical scar, the larger of them measuring 15 mm in diameter (Figure, A) and the smaller of them measuring 4 mm. When the arm was abducted to 90°, the patient denied pain but described a subtle tightness sensation on the arm. An excisional biopsy from the larger lesion was performed (Figure, B-D). ### OUTPUT:

Axillary web syndrome

['Oncology', 'Skin Cancer', 'Melanoma', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 40s with a medical history of multiple sclerosis consulted for the sudden development of 2 adjacent nodules on the left arm. An excision with 1-cm margins of the left arm demonstrated desmoplastic melanoma with a Breslow thickness of 1 mm, and a left axillary sentinel lymph node biopsy (SLNB) had been performed 3 weeks before under general anesthesia. The patient was also being treated with subcutaneous interferon beta 1a for the multiple sclerosis. Physical examination revealed 2 indurated and mobile subcutaneous nodules on the anterior surface of the arm 5 cm distal to the surgical scar, the larger of them measuring 15 mm in diameter (Figure, A) and the smaller of them measuring 4 mm. When the arm was abducted to 90°, the patient denied pain but described a subtle tightness sensation on the arm. An excisional biopsy from the larger lesion was performed (Figure, B-D). ### OUTPUT:

JAMA_FINAL159

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 40s was seen in clinic for a long history of palpitations. He had a history of cardiac arrest after receiving adenosine for sustained supraventricular tachycardia and tachycardia-induced cardiomyopathy. The patient was also noted to have episodes of atrial flutter. Transthoracic echocardiogram displayed a left ventricular ejection fraction of 63% and mild aortic and mitral regurgitation. Cardiac magnetic resonance imaging in sinus rhythm showed mild left ventricle thickening (up to 14 mm) and was otherwise normal. The patient was hospitalized for initiation of sotalol, given that he experienced frequent episodes of atrial arrhythmia. Figure 1A shows sinus rhythm prior to sotalol initiation. Figure 1B shows telemetry during administration of sotalol. ### OUTPUT:

Latent accessory pathway (Wolff-Parkinson-White syndrome)

['Rhythm Disorders', 'Cardiology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 40s was seen in clinic for a long history of palpitations. She had a history of cardiac arrest after receiving adenosine for sustained supraventricular tachycardia and tachycardia-induced cardiomyopathy. The patient was also noted to have episodes of atrial flutter. Transthoracic echocardiogram displayed a left ventricular ejection fraction of 63% and mild aortic and mitral regurgitation. Cardiac magnetic resonance imaging in sinus rhythm showed mild left ventricle thickening (up to 14 mm) and was otherwise normal. The patient was hospitalized for initiation of sotalol, given that she experienced frequent episodes of atrial arrhythmia. Figure 1A shows sinus rhythm prior to sotalol initiation. Figure 1B shows telemetry during administration of sotalol. ### OUTPUT:

JAMA_FINAL160

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old man with advanced primary open-angle glaucoma presented with 1 day of decreased vision and eye pain. He had undergone trabeculectomy and 5-fluorouracil injection 1 month prior. On initial examination, his visual acuity was 20/25. He had diffuse conjunctival hyperemia without bleb purulence or leakage and more than 50 cells per high-power field of a 1 × 1-mm area of light on slitlamp biomicroscopy. He was treated for blebitis with topical fortified antibiotics but subsequently developed vitritis. He underwent vitreous tap and injection of vancomycin and amikacin followed by pars plana vitrectomy with bleb revision. Separate vitreous samples from each procedure were sent for Gram stain and bacterial and fungal culture on chocolate and Sabouraud agar with no growth. His eye pain worsened significantly, and ultrasound biomicroscopy showed scleral thickening (Figure 1A). Lab workup for autoimmune scleritis including tests for rheumatoid factor, antinuclear antibodies, and antineutrophil cytoplasmic antibodies was negative. He was admitted to the hospital and started intravenous vancomycin and piperacillin-tazobactam treatment. His vision continued to decline to counting fingers because of the development of a dense cataract with retrolenticular plaque (Figure 1B). ### OUTPUT:

Aspergillus fumigatus endophthalmitis and scleritis

['Fungal Infections', 'Infectious Diseases', 'Ophthalmology', 'Glaucoma']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old woman with advanced primary open-angle glaucoma presented with 1 day of decreased vision and eye pain. She had undergone trabeculectomy and 5-fluorouracil injection 1 month prior. On initial examination, her visual acuity was 20/25. She had diffuse conjunctival hyperemia without bleb purulence or leakage and more than 50 cells per high-power field of a 1 × 1-mm area of light on slitlamp biomicroscopy. She was treated for blebitis with topical fortified antibiotics but subsequently developed vitritis. She underwent vitreous tap and injection of vancomycin and amikacin followed by pars plana vitrectomy with bleb revision. Separate vitreous samples from each procedure were sent for Gram stain and bacterial and fungal culture on chocolate and Sabouraud agar with no growth. Her eye pain worsened significantly, and ultrasound biomicroscopy showed scleral thickening (Figure 1A). Lab workup for autoimmune scleritis including tests for rheumatoid factor, antinuclear antibodies, and antineutrophil cytoplasmic antibodies was negative. She was admitted to the hospital and started intravenous vancomycin and piperacillin-tazobactam treatment. Her vision continued to decline to counting fingers because of the development of a dense cataract with retrolenticular plaque (Figure 1B). ### OUTPUT:

JAMA_FINAL161

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 57-year-old man presented to the emergency department with 5 months of epigastric pain and a 6.8-kg (15-lb) weight loss. He had no fevers or night sweats. Physical examination was notable for oral thrush and mild epigastric tenderness. Results of a fourth-generation HIV Ab/Ag combination assay were positive, and subsequent testing showed a CD4 cell count of 16/mm3 and an HIV viral load greater than 10 million copies/mL. Computed tomography of the abdomen and pelvis showed thickening of the walls of the stomach, duodenum, and colon as well as multiple masses in the right hepatic lobe measuring up to 6.9 cm in diameter. A core biopsy of one of the liver masses demonstrated diffuse large B-cell lymphoma. He started antiretroviral therapy with bictegravir/emtricitabine/tenofovir/alafenamide and chemotherapy with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). Four weeks after initiation of chemotherapy, the patient developed sudden onset of bright red blood per rectum, tachycardia, and hypotension. Mesenteric computed tomography angiography demonstrated active extravasation in the jejunum from a branch of the superior mesenteric artery. After unsuccessful coil embolization, he underwent open resection of 40 cm of distal small intestine; pathological examination of a stained section showed acute inflammation of the lamina propria, with crypt epithelial apoptosis and numerous cytoplasmic and nuclear inclusions with an “owl eye” appearance (Figure 1, left panel). Five weeks later, he developed blurred vision, and visual acuity testing revealed 20/50 vision in the left eye and 20/70 in the right eye. A dilated retinal examination revealed extensive macular hemorrhage in the left eye, with peripapillary whitening and perivascular hemorrhage with whitening along the superior vascular arcade (Figure, right panel). ### OUTPUT:

Cytomegalovirus (CMV) retinitis and hemorrhagic enteritis

['Bleeding and Transfusion', 'Gastroenterology', 'Gastroenterology and Hepatology', 'Ophthalmology', 'HIV']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 57-year-old woman presented to the emergency department with 5 months of epigastric pain and a 6.8-kg (15-lb) weight loss. She had no fevers or night sweats. Physical examination was notable for oral thrush and mild epigastric tenderness. Results of a fourth-generation HIV Ab/Ag combination assay were positive, and subsequent testing showed a CD4 cell count of 16/mm3 and an HIV viral load greater than 10 million copies/mL. Computed tomography of the abdomen and pelvis showed thickening of the walls of the stomach, duodenum, and colon as well as multiple masses in the right hepatic lobe measuring up to 6.9 cm in diameter. A core biopsy of one of the liver masses demonstrated diffuse large B-cell lymphoma. She started antiretroviral therapy with bictegravir/emtricitabine/tenofovir/alafenamide and chemotherapy with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). Four weeks after initiation of chemotherapy, the patient developed sudden onset of bright red blood per rectum, tachycardia, and hypotension. Mesenteric computed tomography angiography demonstrated active extravasation in the jejunum from a branch of the superior mesenteric artery. After unsuccessful coil embolization, she underwent open resection of 40 cm of distal small intestine; pathological examination of a stained section showed acute inflammation of the lamina propria, with crypt epithelial apoptosis and numerous cytoplasmic and nuclear inclusions with an “owl eye” appearance (Figure 1, left panel). Five weeks later, she developed blurred vision, and visual acuity testing revealed 20/50 vision in the left eye and 20/70 in the right eye. A dilated retinal examination revealed extensive macular hemorrhage in the left eye, with peripapillary whitening and perivascular hemorrhage with whitening along the superior vascular arcade (Figure, right panel). ### OUTPUT:

JAMA_FINAL162

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 49-year-old man with a history of diabetes, hypertension, intravenous drug abuse, and multiple sexual partners presented to the emergency department with painless vision loss in both eyes for 10 days, left eye worse than right eye, and photophobia in both eyes. His visual acuity was count fingers OD and 20/70 OS. Intraocular pressure was 20 mm Hg OD and 16 mm Hg OS. There were 1+ (10-12 cells/high-power field) anterior chamber cells in both eyes with very hazy posterior pole details in the right eye and minimal vitreous haze in the left eye. There was a hazy view to the posterior pole in the right eye with disc edema and multiple flame hemorrhages surrounding the nerve. Examination of the posterior pole in the left eye revealed partial obstruction of all vessels and a complete halo on the disc with numerous flame hemorrhages emanating from and surrounding the optic nerve, along with a few dot blot hemorrhages within the macula (Figure). His blood pressure was 173/137 mm Hg, but the rest of his vital signs were normal. ### OUTPUT:

Syphilitic panuveitis and optic neuritis

['Infectious Diseases', 'Neuro-ophthalmology', 'Sexually Transmitted Infections', 'Retinal Disorders', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 49-year-old woman with a history of diabetes, hypertension, intravenous drug abuse, and multiple sexual partners presented to the emergency department with painless vision loss in both eyes for 10 days, left eye worse than right eye, and photophobia in both eyes. Her visual acuity was count fingers OD and 20/70 OS. Intraocular pressure was 20 mm Hg OD and 16 mm Hg OS. There were 1+ (10-12 cells/high-power field) anterior chamber cells in both eyes with very hazy posterior pole details in the right eye and minimal vitreous haze in the left eye. There was a hazy view to the posterior pole in the right eye with disc edema and multiple flame hemorrhages surrounding the nerve. Examination of the posterior pole in the left eye revealed partial obstruction of all vessels and a complete halo on the disc with numerous flame hemorrhages emanating from and surrounding the optic nerve, along with a few dot blot hemorrhages within the macula (Figure). Her blood pressure was 173/137 mm Hg, but the rest of her vital signs were normal. ### OUTPUT:

JAMA_FINAL163

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A male in his late teens presented with asymptomatic congenital papules, plaques, and nodules in a linear bilateral distribution following Blaschko lines on the scalp and face region. The papules and nodules appeared to grow as the boy grew, and some pedunculated lesions tended to fall off spontaneously. He had not received any prior treatment. The patient had no other significant medical history and denied having a family history of similar lesions. Clinical examination findings revealed multiple skin-colored, nontender soft papules of varying sizes protruding from the skin surface on the right cheek, forehead, and jaw, as well as on the anterior surface of the scalp, distributed along Blaschko lines, with sparse vellus hairs and multiple hair follicles on the lesions (Figure, A and B). However, no hair was observed on the lesion because the patient had shaved the hair on his face. An incisional biopsy of a pedunculated lesion above the left eyebrow was performed (Figure, B). ### OUTPUT:

Hair follicle nevus

['Dermatology', 'Hair Disorders', 'Nevi', 'Pediatrics', 'Adolescent Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Hair follicle nevus. Case report: A female in her late teens presented with asymptomatic congenital papules, plaques, and nodules in a linear bilateral distribution following Blaschko lines on the scalp and face region. The papules and nodules appeared to grow as the girl grew, and some pedunculated lesions tended to fall off spontaneously. She had not received any prior treatment. The patient had no other significant medical history and denied having a family history of similar lesions. Clinical examination findings revealed multiple skin-colored, nontender soft papules of varying sizes protruding from the skin surface on the right cheek, forehead, and jaw, as well as on the anterior surface of the scalp, distributed along Blaschko lines, with sparse vellus hairs and multiple hair follicles on the lesions (Figure, A and B). However, no hair was observed on the lesion because the patient had shaved the hair on her face. An incisional biopsy of a pedunculated lesion above the left eyebrow was performed (Figure, B). ### OUTPUT:

JAMA_FINAL164

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy 25-year-old woman presented with headache, dysarthria, double vision, and dizziness for 1 week. She denied any history of fever, head trauma, vomiting, diarrhea, abdominal pain, or cough. She had traveled to northeastern Brazil 2 months before the onset of the neurological symptoms. On examination, she had a mild right-side hemiparesis with hyperreflexia and hemiataxia. She could walk unassisted but presented with a broad base. There were no meningeal signs. She did not present with hepatosplenomegaly of lymphadenopathy. Her cranial magnetic resonance imaging showed a T2-weighted fluid-attenuated inversion recovery hyperintense lesion with heterogeneous gadolinium enhancement in the pons (Figure). There were no signs of diffusion restriction on diffusion-weighted imaging or hemorrhages on susceptibility-weighted imaging. ### OUTPUT:

Neuroschistosomiasis

['Infectious Diseases', 'Neurology', 'CNS Infections', 'Radiology', 'Neuroimaging']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy 25-year-old man presented with headache, dysarthria, double vision, and dizziness for 1 week. He denied any history of fever, head trauma, vomiting, diarrhea, abdominal pain, or cough. He had traveled to northeastern Brazil 2 months before the onset of the neurological symptoms. On examination, he had a mild right-side hemiparesis with hyperreflexia and hemiataxia. He could walk unassisted but presented with a broad base. There were no meningeal signs. He did not present with hepatosplenomegaly of lymphadenopathy. His cranial magnetic resonance imaging showed a T2-weighted fluid-attenuated inversion recovery hyperintense lesion with heterogeneous gadolinium enhancement in the pons (Figure). There were no signs of diffusion restriction on diffusion-weighted imaging or hemorrhages on susceptibility-weighted imaging. ### OUTPUT:

JAMA_FINAL165

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 20s was referred for evaluation of a 4-year history of recurrent pustular eruptions on her face, which initially presented while she was vacationing in Florida. She noted mild associated pruritus but denied burning sensation. The eruptions occurred intermittently, appearing as erythematous papules with prominent pustules, and were exacerbated by sunlight. On average, her lesions would resolve in 3 to 4 days with only mild background erythema by 5 to 7 days. Even mild sun exposure would induce the eruption, leading to frequent recurrences in summer months but long periods of remission in the fall through spring. Trials with various broad-spectrum sunscreens in combination with topical and oral antibiotics and topical ivermectin did not prevent flares or mitigate severity of eruptions when they occurred. She denied joint pain, fever, fatigue, changes in urine color, use of other topical or systemic medications, or presence of rashes elsewhere. She was otherwise healthy without other medical history. On physical examination, she was well appearing with numerous 1- to 2-mm monomorphous pustules over background erythema on the medial cheeks, chin, and nose (Figure, A). No nail fold capillary changes or mucosal lesions were observed. Serum analysis results for antinuclear, anti-SSA/Ro, and anti-SSB/La antibodies were negative. A 4-mm punch biopsy was taken from a representative lesion along the right jawline (Figure, B-D). ### OUTPUT:

Actinic folliculitis

['Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 20s was referred for evaluation of a 4-year history of recurrent pustular eruptions on his face, which initially presented while he was vacationing in Florida. He noted mild associated pruritus but denied burning sensation. The eruptions occurred intermittently, appearing as erythematous papules with prominent pustules, and were exacerbated by sunlight. On average, his lesions would resolve in 3 to 4 days with only mild background erythema by 5 to 7 days. Even mild sun exposure would induce the eruption, leading to frequent recurrences in summer months but long periods of remission in the fall through spring. Trials with various broad-spectrum sunscreens in combination with topical and oral antibiotics and topical ivermectin did not prevent flares or mitigate severity of eruptions when they occurred. He denied joint pain, fever, fatigue, changes in urine color, use of other topical or systemic medications, or presence of rashes elsewhere. He was otherwise healthy without other medical history. On physical examination, he was well appearing with numerous 1- to 2-mm monomorphous pustules over background erythema on the medial cheeks, chin, and nose (Figure, A). No nail fold capillary changes or mucosal lesions were observed. Serum analysis results for antinuclear, anti-SSA/Ro, and anti-SSB/La antibodies were negative. A 4-mm punch biopsy was taken from a representative lesion along the right jawline (Figure, B-D). ### OUTPUT:

JAMA_FINAL166

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 39-year-old healthy woman without family history of malignancy found a mass in her right breast at 38 weeks of pregnancy. Prior to delivery, she underwent diagnostic ultrasound of the right breast, which showed a possible mass in the location of the palpable lesion that was most consistent with a normal island of fibroglandular tissue. Follow-up mammogram and ultrasound of the right breast (without axillary evaluation) were performed 6 months later, which showed an irregular 17-mm mass with associated pleomorphic calcifications in the same area. Ultrasound-guided biopsy was performed. Pathology showed high-grade, estrogen receptor–positive ductal carcinoma in situ (DCIS). On postbiopsy physical examination, the patient had a palpable 2.5-cm right breast mass at the 3-o’clock position without palpable axillary lymphadenopathy. Surgical treatment with lumpectomy was recommended, and breast magnetic resonance imaging (MRI) was performed prior to surgery to evaluate the extent of disease (Figure). Axial T2-weighted MRI at the level of the axilla revealed edema surrounding 2 enlarged, morphologically abnormal right level-1 axillary lymph nodes; axial postcontrast T1 fat-saturated MRI of the right breast revealed an irregular mass with irregular margins at the site of biopsy-proven DCIS. The patient reported receiving her second dose of COVID-19 vaccine (Pfizer-BioNTech) in the right arm the day before the breast MRI. ### OUTPUT:

Vaccination-associated reactive lymphadenopathy

['Breast Cancer', 'Oncology', 'Radiology', "Women's Health", 'Vaccination']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Vaccination-associated reactive lymphadenopathy. Case report: A 39-year-old healthy man without family history of malignancy found a mass in his right breast at 38 weeks of his partner's pregnancy. Prior to delivery, he underwent diagnostic ultrasound of the right breast, which showed a possible mass in the location of the palpable lesion that was most consistent with a normal island of fibroglandular tissue. Follow-up mammogram and ultrasound of the right breast (without axillary evaluation) were performed 6 months later, which showed an irregular 17-mm mass with associated pleomorphic calcifications in the same area. Ultrasound-guided biopsy was performed. Pathology showed high-grade, estrogen receptor–positive ductal carcinoma in situ (DCIS). On postbiopsy physical examination, the patient had a palpable 2.5-cm right breast mass at the 3-o’clock position without palpable axillary lymphadenopathy. Surgical treatment with lumpectomy was recommended, and breast magnetic resonance imaging (MRI) was performed prior to surgery to evaluate the extent of disease (Figure). Axial T2-weighted MRI at the level of the axilla revealed edema surrounding 2 enlarged, morphologically abnormal right level-1 axillary lymph nodes; axial postcontrast T1 fat-saturated MRI of the right breast revealed an irregular mass with irregular margins at the site of biopsy-proven DCIS. The patient reported receiving his second dose of COVID-19 vaccine (Pfizer-BioNTech) in the right arm the day before the breast MRI. ### OUTPUT:

JAMA_FINAL167

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 12-year-old girl presented for assessment of abnormal gait. A year prior, she was found to have bilateral panuveitis with occlusive retinal periphlebitis involving all quadrants of the central and peripheral retina with capillary nonperfusion (Figure 1). Her subsequent workup revealed elevated inflammatory markers and subcentimeter chest and abdominal lymph nodes. Given a positive interferon-γ release assay, therapy was initiated with rifampin, isoniazid, pyrazinamide, ethambutol (RIPE) and corticosteroids for presumed tuberculosis. ### OUTPUT:

Pediatric neurosarcoidosis

['Adolescent Medicine', 'Neuro-ophthalmology', 'Neurology', 'Ophthalmology', 'Intraocular Inflammation']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Pediatric neurosarcoidosis. Case report: A 12-year-old boy presented for assessment of abnormal gait. A year prior, he was found to have bilateral panuveitis with occlusive retinal periphlebitis involving all quadrants of the central and peripheral retina with capillary nonperfusion (Figure 1). His subsequent workup revealed elevated inflammatory markers and subcentimeter chest and abdominal lymph nodes. Given a positive interferon-γ release assay, therapy was initiated with rifampin, isoniazid, pyrazinamide, ethambutol (RIPE) and corticosteroids for presumed tuberculosis. ### OUTPUT:

JAMA_FINAL168

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 51-year-old woman presented with a 1-month history of intense and worsening polyarthralgia and swelling of bilateral fingers and toes. There was no history of alopecia, oral ulcers, rashes, or Raynaud phenomenon. She did not report preceding fever, diarrhea, or dysuria. There was no history of weight loss or anorexia. Medical history included tertiary hyperparathyroidism related to end-stage kidney disease from chronic glomerulonephritis. The patient had successfully received an ABO-incompatible kidney transplant 1 year ago, but this was complicated by invasive fungal (Volvariella volvacea) infection of the central nervous system. Medications included tacrolimus (0.5 mg twice daily), prednisolone (10 mg daily), cinacalcet (12.5 mg daily), and voriconazole (500 mg daily). On examination, her fingers and toes were symmetrically and diffusely swollen and tender. There was no rash, enthesitis, psoriatic nail changes, clubbing, or lower limb edema. The rest of the physical examination was unremarkable. Alkaline phosphatase level was elevated at 640 U/L (10.69 μkat/L) (reference range, 40-130 U/L [0.67-2.17 μkat/L]). Corrected calcium and parathyroid hormone levels were 10.88 mg/dL (2.71 mmol/L) (reference range, 8.6-10.2 mg/dL [2.15-2.55 mmol/L]) and 23.7 pmol/L (reference range, 1.3-9.3), respectively. Serum bilirubin, aspartate transferase, alanine transferase, creatinine, and phosphate levels were within reference ranges. Free thyroxine and thyrotropin levels were normal. Results of testing for rheumatoid factor and anti-citrullinated protein antibody were negative. Her chest radiograph was unremarkable. Radiography of her hands was performed (Figure). ### OUTPUT:

Voriconazole-induced periostitis

['Clinical Pharmacy and Pharmacology', 'Nephrology', 'Rheumatology', 'Transplantation', 'Adverse Drug Events']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 51-year-old man presented with a 1-month history of intense and worsening polyarthralgia and swelling of bilateral fingers and toes. There was no history of alopecia, oral ulcers, rashes, or Raynaud phenomenon. He did not report preceding fever, diarrhea, or dysuria. There was no history of weight loss or anorexia. Medical history included tertiary hyperparathyroidism related to end-stage kidney disease from chronic glomerulonephritis. The patient had successfully received an ABO-incompatible kidney transplant 1 year ago, but this was complicated by invasive fungal (Volvariella volvacea) infection of the central nervous system. Medications included tacrolimus (0.5 mg twice daily), prednisolone (10 mg daily), cinacalcet (12.5 mg daily), and voriconazole (500 mg daily). On examination, his fingers and toes were symmetrically and diffusely swollen and tender. There was no rash, enthesitis, psoriatic nail changes, clubbing, or lower limb edema. The rest of the physical examination was unremarkable. Alkaline phosphatase level was elevated at 640 U/L (10.69 μkat/L) (reference range, 40-130 U/L [0.67-2.17 μkat/L]). Corrected calcium and parathyroid hormone levels were 10.88 mg/dL (2.71 mmol/L) (reference range, 8.6-10.2 mg/dL [2.15-2.55 mmol/L]) and 23.7 pmol/L (reference range, 1.3-9.3), respectively. Serum bilirubin, aspartate transferase, alanine transferase, creatinine, and phosphate levels were within reference ranges. Free thyroxine and thyrotropin levels were normal. Results of testing for rheumatoid factor and anti-citrullinated protein antibody were negative. His chest radiograph was unremarkable. Radiography of his hands was performed (Figure). ### OUTPUT:

JAMA_FINAL169

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old man was referred for evaluation of a retinal detachment in his left eye. His visual acuity on presentation was 20/20 in the right eye and hand motion only in the left eye. Examination of the right eye was normal. Anterior segment examination of the left eye revealed around 30 cells per high-power field of a 1 mm × 1 mm light beam and diffuse stellate-appearing keratic precipitates. Posterior examination results showed a vitreous cell that precluded a clear view of the posterior pole and inferior snow banking. Most notable was a large, white, preretinal lesion in the inferior macula and a near-total retinal detachment with no identifiable retinal break and shifting subretinal fluid (Figure). ### OUTPUT:

Ocular and disseminated toxoplasmosis with toxoplasmic myocarditis

['Global Health', 'Infectious Diseases', 'Ophthalmology', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old woman was referred for evaluation of a retinal detachment in her left eye. Her visual acuity on presentation was 20/20 in the right eye and hand motion only in the left eye. Examination of the right eye was normal. Anterior segment examination of the left eye revealed around 30 cells per high-power field of a 1 mm × 1 mm light beam and diffuse stellate-appearing keratic precipitates. Posterior examination results showed a vitreous cell that precluded a clear view of the posterior pole and inferior snow banking. Most notable was a large, white, preretinal lesion in the inferior macula and a near-total retinal detachment with no identifiable retinal break and shifting subretinal fluid (Figure). ### OUTPUT:

JAMA_FINAL170

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 17-year-old previously healthy girl presented with 3 months of decreased vision in the right eye associated with throbbing pain with eye movement. The patient had no history of weakness, incontinence, or severe headaches. Initial presentation was notable for hand motion visual acuity with a 2+ relative afferent pupillary defect on the right; fundus examination revealed grade IV disc edema with obscuration of all major vessels on the disc (Figure, A). A magnetic resonance image (MRI) of the brain with and without gadolinium contrast was degraded by motion and orthodontic artifact but was suggestive of optic nerve enhancement consistent with optic neuritis. Results of serology tests and cerebral spinal fluid analysis were negative for infectious and inflammatory etiologies, including syphilis, sarcoidosis, Lyme disease, viral etiologies, multiple sclerosis, and lupus. ### OUTPUT:

Pilocytic astrocytoma with anaplastic transformation

['Neuro-oncology', 'Neuro-ophthalmology', 'Neurology', 'Intraocular Tumors', 'Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 17-year-old previously healthy boy presented with 3 months of decreased vision in the right eye associated with throbbing pain with eye movement. The patient had no history of weakness, incontinence, or severe headaches. Initial presentation was notable for hand motion visual acuity with a 2+ relative afferent pupillary defect on the right; fundus examination revealed grade IV disc edema with obscuration of all major vessels on the disc (Figure, A). A magnetic resonance image (MRI) of the brain with and without gadolinium contrast was degraded by motion and orthodontic artifact but was suggestive of optic nerve enhancement consistent with optic neuritis. Results of serology tests and cerebral spinal fluid analysis were negative for infectious and inflammatory etiologies, including syphilis, sarcoidosis, Lyme disease, viral etiologies, multiple sclerosis, and lupus. ### OUTPUT:

JAMA_FINAL171

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 46-year-old man presented with acute-onset weakness of his bilateral lower limbs for 3 days, accompanied by ascending numbness to just below his nipples. Three weeks prior, he had developed acute urinary retention. Neurological examination revealed weakness in bilateral lower limbs (Medical Research Council grade 4 on the right and grade 3 on the left), extensor plantar responses, and a sensory level at T6. Magnetic resonance imaging of his thoracic spine was performed 10 days after the onset of weakness and did not show any signal abnormalities or restricted diffusion. Cerebrospinal fluid analysis findings were remarkable for elevated protein (0.14 g/dL [to convert to grams per liter, multiply by 10]) but white cell count (5 cells/mm3) and glucose levels (54.05 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) were normal. Cytology and flow cytometry were negative for malignancy. Antibodies to aquaporin 4 and myelin oligodendrocyte glycoprotein were not detected. The patient developed a sudden worsening of weakness in his legs 2 weeks after initial presentation. Repeated thoracic spine imaging showed an area of T2 hyperintensity in the left posterolateral cord at T7, which did not enhance with contrast or show restricted diffusion (Figure 1A). Notably, he had a 4-year history of an asymptomatic papular skin eruption with more lesions developing in the last 4 months. These were distributed on the neck, trunk, and limbs, sparing his face, scalp, and genitalia (Figure 1B). Findings of extensive workup for malignancy, including full-body computed tomography scan, paraneoplastic antibody panel, and systemic autoimmune diseases (antinuclear antibody, antidouble stranded DNA, and myositis antibody panel), were negative. The skin papules were biopsied. ### OUTPUT:

Malignant atrophic papulosis

['Dermatology', 'Neurology', 'Spinal Cord Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 46-year-old woman presented with acute-onset weakness of her bilateral lower limbs for 3 days, accompanied by ascending numbness to just below her nipples. Three weeks prior, she had developed acute urinary retention. Neurological examination revealed weakness in bilateral lower limbs (Medical Research Council grade 4 on the right and grade 3 on the left), extensor plantar responses, and a sensory level at T6. Magnetic resonance imaging of her thoracic spine was performed 10 days after the onset of weakness and did not show any signal abnormalities or restricted diffusion. Cerebrospinal fluid analysis findings were remarkable for elevated protein (0.14 g/dL [to convert to grams per liter, multiply by 10]) but white cell count (5 cells/mm3) and glucose levels (54.05 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) were normal. Cytology and flow cytometry were negative for malignancy. Antibodies to aquaporin 4 and myelin oligodendrocyte glycoprotein were not detected. The patient developed a sudden worsening of weakness in her legs 2 weeks after initial presentation. Repeated thoracic spine imaging showed an area of T2 hyperintensity in the left posterolateral cord at T7, which did not enhance with contrast or show restricted diffusion (Figure 1A). Notably, she had a 4-year history of an asymptomatic papular skin eruption with more lesions developing in the last 4 months. These were distributed on the neck, trunk, and limbs, sparing her face, scalp, and genitalia (Figure 1B). Findings of extensive workup for malignancy, including full-body computed tomography scan, paraneoplastic antibody panel, and systemic autoimmune diseases (antinuclear antibody, antidouble stranded DNA, and myositis antibody panel), were negative. The skin papules were biopsied. ### OUTPUT:

JAMA_FINAL172

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 30s, employed as a painter, presented with multiple painless nodules on his right cheek of 4 years’ duration. He reported episodic breathlessness, cough, and wheezing with expectoration of brownish sputum, exacerbated with exposure to hay dust, in the past 5 years. He also reported recent-onset headache while reading. Physical examination revealed a depressed plaque measuring 6 × 4 cm in the right infraorbital region, surrounded by multiple nodules of sizes ranging from 1 × 1 cm to 5 × 1 cm (Figure, A). The nodules were firm, mobile, and nontender on palpation. Local temperature was normal. There was proptosis of the right eye with mild restriction of extraocular movements on lateral gaze. Examination of the oral cavity revealed dental caries, while gingivolabial sulcus was free on bidigital examination. Nasal mucosa was normal. Respiratory system examination revealed occasional polyphonic wheeze. Chest radiography imaging showed nodular opacities in right upper zone and bronchiectasis. Punch biopsy from 1 nodule was sent for histopathological and microbiological examination (Figure, B and C). ### OUTPUT:

Cutaneous aspergillosis

['Dermatology', 'Fungal Infections', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 30s, employed as a painter, presented with multiple painless nodules on her right cheek of 4 years’ duration. She reported episodic breathlessness, cough, and wheezing with expectoration of brownish sputum, exacerbated with exposure to hay dust, in the past 5 years. She also reported recent-onset headache while reading. Physical examination revealed a depressed plaque measuring 6 × 4 cm in the right infraorbital region, surrounded by multiple nodules of sizes ranging from 1 × 1 cm to 5 × 1 cm (Figure, A). The nodules were firm, mobile, and nontender on palpation. Local temperature was normal. There was proptosis of the right eye with mild restriction of extraocular movements on lateral gaze. Examination of the oral cavity revealed dental caries, while gingivolabial sulcus was free on bidigital examination. Nasal mucosa was normal. Respiratory system examination revealed occasional polyphonic wheeze. Chest radiography imaging showed nodular opacities in right upper zone and bronchiectasis. Punch biopsy from 1 nodule was sent for histopathological and microbiological examination (Figure, B and C). ### OUTPUT:

JAMA_FINAL173

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 69-year-old man presented with a 1-month history of progressive skin discoloration. His medical history included chronic kidney disease, chronic hepatitis C infection, cirrhosis, ischemic cardiomyopathy with an implantable cardioverter-defibrillator (ICD), and atrial fibrillation with prophylactic apixaban. He had recurrent staphylococcus bacteremia due to infection of an ICD lead and had been treated for the past 6 months with minocycline, 100 mg twice daily. His arms had been purple and bruise-like for several years but turned a near black color 1 month ago. He reported no discoloration of his sweat or urine. He had no history of malnutrition and reported infrequent alcohol use. Physical examination showed dense blue-black skin pigmentation of his forearms, dorsal hands, legs, and dorsal feet, as well as blue discoloration of his sclerae and teeth (Figure 1). He had normal-colored nails and oral mucosa. Laboratory studies showed white blood cell count of 15 800/μL (reference range, 4000-11 000/μL), hemoglobin of 10.7 g/dL (reference, 13.5-17.5 g/dL), platelet count of 58 000/μL (reference, 150 000-400 000/μL), and INR of 1.8 (reference, 0.8-1.1). Complete metabolic panel showed increased creatinine (1.51 mg/dL; reference, 0.64-1.27 mg/dL) and elevated total bilirubin (1.7 mg/dL; reference range, 0.3-1.2 mg/dL). His estimated glomerular filtration rate was 40 mL/min/1.73 m2. ### OUTPUT:

Minocycline-induced hyperpigmentation

['Dermatology', 'Clinical Pharmacy and Pharmacology', 'External Eye Disease', 'Ophthalmology', 'Adverse Drug Events']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 69-year-old woman presented with a 1-month history of progressive skin discoloration. Her medical history included chronic kidney disease, chronic hepatitis C infection, cirrhosis, ischemic cardiomyopathy with an implantable cardioverter-defibrillator (ICD), and atrial fibrillation with prophylactic apixaban. She had recurrent staphylococcus bacteremia due to infection of an ICD lead and had been treated for the past 6 months with minocycline, 100 mg twice daily. Her arms had been purple and bruise-like for several years but turned a near black color 1 month ago. She reported no discoloration of her sweat or urine. She had no history of malnutrition and reported infrequent alcohol use. Physical examination showed dense blue-black skin pigmentation of her forearms, dorsal hands, legs, and dorsal feet, as well as blue discoloration of her sclerae and teeth (Figure 1). She had normal-colored nails and oral mucosa. Laboratory studies showed white blood cell count of 15 800/μL (reference range, 4000-11 000/μL), hemoglobin of 10.7 g/dL (reference, 13.5-17.5 g/dL), platelet count of 58 000/μL (reference, 150 000-400 000/μL), and INR of 1.8 (reference, 0.8-1.1). Complete metabolic panel showed increased creatinine (1.51 mg/dL; reference, 0.64-1.27 mg/dL) and elevated total bilirubin (1.7 mg/dL; reference range, 0.3-1.2 mg/dL). Her estimated glomerular filtration rate was 40 mL/min/1.73 m2. ### OUTPUT:

JAMA_FINAL174

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 46-year-old man presented with a 2-week history of a persistent blurred area in his right lower visual field of both eyes. He noticed colors surrounding the dark area that lasted 2 to 3 minutes at a time and occurred multiple times per day. His medical history was significant for dyslipidemia for which he took rosuvastatin. He also reported feeling lethargic, with polydipsia and a dull mild holocephalic headache during this period. Ophthalmological examination revealed a visual acuity of 20/20 OU, pupils were equal and reactive to light with no relative afferent pupillary defect, and color vision was normal. Dilated fundus examination was normal. Humphrey 24-2 Swedish interactive threshold algorithm fast visual field testing revealed a right homonymous hemianopia denser inferiorly (Figure, A). An urgent noncontrast computed tomography (CT) scan of the head was obtained and was normal (Figure, B). Magnetic resonance imaging (MRI) of the brain was initially reported as normal but revealed subtle abnormal T2/fluid-attenuated inversion recovery hyperintensity involving the left occipital cortex after further review (Figure, B). ### OUTPUT:

Homonymous hemianopia secondary to nonketotic hyperglycemia

['Neurology', 'Ophthalmology', 'Diabetes', 'Diabetes and Endocrinology', 'Neuroimaging']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 46-year-old woman presented with a 2-week history of a persistent blurred area in her right lower visual field of both eyes. She noticed colors surrounding the dark area that lasted 2 to 3 minutes at a time and occurred multiple times per day. Her medical history was significant for dyslipidemia for which she took rosuvastatin. She also reported feeling lethargic, with polydipsia and a dull mild holocephalic headache during this period. Ophthalmological examination revealed a visual acuity of 20/20 OU, pupils were equal and reactive to light with no relative afferent pupillary defect, and color vision was normal. Dilated fundus examination was normal. Humphrey 24-2 Swedish interactive threshold algorithm fast visual field testing revealed a right homonymous hemianopia denser inferiorly (Figure, A). An urgent noncontrast computed tomography (CT) scan of the head was obtained and was normal (Figure, B). Magnetic resonance imaging (MRI) of the brain was initially reported as normal but revealed subtle abnormal T2/fluid-attenuated inversion recovery hyperintensity involving the left occipital cortex after further review (Figure, B). ### OUTPUT:

JAMA_FINAL175

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old woman was referred by optometry after waking up with cloudy vision in the left eye and an ache around the left brow. Visual acuity was 20/20 OD and light perception OS. Intraocular pressure (IOP) was 15 mm Hg OD and 54 mm Hg OS. Anterior segment examination of the left eye was remarkable for a large cystic iris stromal lesion from the 2- to 7-o’clock position with iris-cornea touch. The anterior chamber was shallow in the area of the enlarged cystic lesion with a large amount of pigmented cells. The pupil was irregular with blood at the pupillary margin. Her intraocular lens was not visible because of occlusion by a cystic lesion behind the iris (Figure 1). Her ocular history was notable for indiscriminate trauma to her left eye, primary open-angle glaucoma in both eyes treated with dorzolamide hydrochloride and brimonidine tartrate, and pseudophakia in both eyes. Four years prior, an inferior cystic iris stromal lesion was discovered in the left eye that measured approximately 5 × 2 mm in basal dimensions at the slitlamp. Fine-needle aspiration was negative for malignancy, and the lesion was managed by close follow-up. ### OUTPUT:

Secondary angle-closure glaucoma due to sudden enlargement of a cystic iris stromal lesion

['Glaucoma', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old man was referred by optometry after waking up with cloudy vision in the left eye and an ache around the left brow. Visual acuity was 20/20 OD and light perception OS. Intraocular pressure (IOP) was 15 mm Hg OD and 54 mm Hg OS. Anterior segment examination of the left eye was remarkable for a large cystic iris stromal lesion from the 2- to 7-o’clock position with iris-cornea touch. The anterior chamber was shallow in the area of the enlarged cystic lesion with a large amount of pigmented cells. The pupil was irregular with blood at the pupillary margin. His intraocular lens was not visible because of occlusion by a cystic lesion behind the iris (Figure 1). His ocular history was notable for indiscriminate trauma to his left eye, primary open-angle glaucoma in both eyes treated with dorzolamide hydrochloride and brimonidine tartrate, and pseudophakia in both eyes. Four years prior, an inferior cystic iris stromal lesion was discovered in the left eye that measured approximately 5 × 2 mm in basal dimensions at the slitlamp. Fine-needle aspiration was negative for malignancy, and the lesion was managed by close follow-up. ### OUTPUT:

JAMA_FINAL176

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 72-year-old woman presented with new-onset decreased vision in the right eye. Her ocular history included pseudoexfoliation syndrome and glaucomatous optic neuropathy in the right eye. Past ocular surgery included uncomplicated trabeculectomy in the right eye treated with mitomycin C (3 months prior) and no ocular surgery history in the left eye. Her medical history included pulmonary Mycobacterium avium infection secondary to hypogammaglobulinemia. Computed tomography scan 2 months prior exhibited reactivation and she started treatment with clarithromycin (1000 mg/d), ethambutol (15 mg/kg/d), and rifabutin (300 mg/d). Best-corrected visual acuity was hand motions OD and 20/20 OS. Intraocular pressures were 4 mm Hg ODand 13 mm Hg OS. Anterior segment examination of the right eye showed substantial conjunctival hyperemia and substantial cellular response in the anterior chamber (2 to 3+) along with a 1-mm hypopyon. There was no leak at the trabeculectomy bleb (negative Seidel test). B-scan ultrasonography showed no retinal detachment or mass. Presumed diagnosis of bleb-related infectious endophthalmitis was made and she was referred for treatment. Pars plana vitrectomy was performed, including vitreous sampling, and showed very light growth of Staphylococcus aureus in 1 colony on 1 plate, which was highly suspicious for contaminant. Intravitreal amikacin and vancomycin were administered after vitreous sampling was performed. Postoperatively, the patient initiated treatment with topical antibiotics and corticosteroids. Her visual acuity returned to 20/30. Two months later, she presented again with a similar acute vision loss in the left eye (counting fingers). Anterior segment examination showed conjunctival hyperemia, cellular reaction, and a small hypopyon (Figure). ### OUTPUT:

Rifabutin-associated uveitis

['Infectious Diseases', 'Ophthalmology', 'Adverse Drug Events', 'Clinical Pharmacy and Pharmacology', 'Glaucoma']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 72-year-old man presented with new-onset decreased vision in the right eye. His ocular history included pseudoexfoliation syndrome and glaucomatous optic neuropathy in the right eye. Past ocular surgery included uncomplicated trabeculectomy in the right eye treated with mitomycin C (3 months prior) and no ocular surgery history in the left eye. His medical history included pulmonary Mycobacterium avium infection secondary to hypogammaglobulinemia. Computed tomography scan 2 months prior exhibited reactivation and he started treatment with clarithromycin (1000 mg/d), ethambutol (15 mg/kg/d), and rifabutin (300 mg/d). Best-corrected visual acuity was hand motions OD and 20/20 OS. Intraocular pressures were 4 mm Hg OD and 13 mm Hg OS. Anterior segment examination of the right eye showed substantial conjunctival hyperemia and substantial cellular response in the anterior chamber (2 to 3+) along with a 1-mm hypopyon. There was no leak at the trabeculectomy bleb (negative Seidel test). B-scan ultrasonography showed no retinal detachment or mass. Presumed diagnosis of bleb-related infectious endophthalmitis was made and he was referred for treatment. Pars plana vitrectomy was performed, including vitreous sampling, and showed very light growth of Staphylococcus aureus in 1 colony on 1 plate, which was highly suspicious for contaminant. Intravitreal amikacin and vancomycin were administered after vitreous sampling was performed. Postoperatively, the patient initiated treatment with topical antibiotics and corticosteroids. His visual acuity returned to 20/30. Two months later, he presented again with a similar acute vision loss in the left eye (counting fingers). Anterior segment examination showed conjunctival hyperemia, cellular reaction, and a small hypopyon (Figure). ### OUTPUT:

JAMA_FINAL177

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A young man presented to the clinic with large, purple plaques on the left lower extremity. The plaques had been present for years, but the patient noted enlargement and darkening for the past 5 years. The lesions were asymptomatic with no associated pruritus, bleeding, or pain. No treatments or diagnostic workup had been attempted prior to presentation. The patient was otherwise healthy and was a never-smoker with no history of hypertension, atherosclerotic disease, or HIV. Physical examination revealed dark violaceous plaques, scattered subcutaneous nodules, and swelling to the mid-shin of the left lower extremity (Figure, A). There was mild warmth noted, but no palpable bruits. Complete metabolic panel, complete blood cell count, prothrombin, and serology were negative or within normal limits. A punch biopsy was performed and submitted for histopathologic analysis (Figure, B). ### OUTPUT:

Stewart-Bluefarb syndrome

['Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A young woman presented to the clinic with large, purple plaques on the left lower extremity. The plaques had been present for years, but the patient noted enlargement and darkening for the past 5 years. The lesions were asymptomatic with no associated pruritus, bleeding, or pain. No treatments or diagnostic workup had been attempted prior to presentation. The patient was otherwise healthy and was a never-smoker with no history of hypertension, atherosclerotic disease, or HIV. Physical examination revealed dark violaceous plaques, scattered subcutaneous nodules, and swelling to the mid-shin of the left lower extremity (Figure, A). There was mild warmth noted, but no palpable bruits. Complete metabolic panel, complete blood cell count, prothrombin, and serology were negative or within normal limits. A punch biopsy was performed and submitted for histopathologic analysis (Figure, B). ### OUTPUT:

JAMA_FINAL178

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 57-year-old man with chronic myelogenous leukemia (CML) refractory to multiple tyrosine kinase inhibitors (ie, imatinib, nilotinib, and bosutinib) presented for subacute-onset blurry vision in both eyes. He had been admitted for an upcoming bone marrow transplant. The patient had floaters without flashes and denied any eye pain. A review of symptoms found chronic fatigue and a new, mild headache beginning a few days prior. On examination, his visual acuity was 20/50 OU; intraocular pressures were 15 mm Hg OD and 13 mm Hg OS; and pupils were equal, round, and reactive, without a relative afferent pupillary defect. Extraocular movements, confrontational visual fields, and Ishihara color plates were full. An anterior segment examination had normal results. A fundus examination revealed clinically significant peripapillary intraretinal and preretinal hemorrhages obscuring the optic disc margins of both eyes (Figure 1). A peripheral retinal examination of both eyes had normal results. ### OUTPUT:

Terson syndrome in a patient with CML with central nervous system involvement

['Neuro-oncology', 'Neuro-ophthalmology', 'Neurology', 'Ophthalmology', 'Hematology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 57-year-old woman with chronic myelogenous leukemia (CML) refractory to multiple tyrosine kinase inhibitors (ie, imatinib, nilotinib, and bosutinib) presented for subacute-onset blurry vision in both eyes. She had been admitted for an upcoming bone marrow transplant. The patient had floaters without flashes and denied any eye pain. A review of symptoms found chronic fatigue and a new, mild headache beginning a few days prior. On examination, her visual acuity was 20/50 OU; intraocular pressures were 15 mm Hg OD and 13 mm Hg OS; and pupils were equal, round, and reactive, without a relative afferent pupillary defect. Extraocular movements, confrontational visual fields, and Ishihara color plates were full. An anterior segment examination had normal results. A fundus examination revealed clinically significant peripapillary intraretinal and preretinal hemorrhages obscuring the optic disc margins of both eyes (Figure 1). A peripheral retinal examination of both eyes had normal results. ### OUTPUT:

JAMA_FINAL179

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 42-year-old woman was referred for ophthalmologic evaluation after developing blurry vision in the right eye 30 days prior. She had a history of hyperlipidemia, hypertension, and migraine headaches. Her medications included atorvastatin, carvedilol, and norethindrone. Dilated-fundus examination of the right eye showed a single cotton-wool spot (indicating local retinal ischemia), with intraretinal hemorrhage in the inferotemporal quadrant. Ultrawide-field imaging showed a cotton-wool spot on the left fundus (Figure 1A, right) and a peripheral arterial occlusion in the right eye (Figure 1A, left), and fluorescein angiographic study of the right eye demonstrated an area of blockage corresponding to intraretinal hemorrhage and venous hyperfluorescence (Figure 1B). The patient was afebrile, with pulse 110 beats/min and blood pressure of 188/99 mm Hg. Auscultation over the heart apex revealed a holosystolic ejection murmur (grade 2/6). Laboratory testing showed normal complete blood cell count and thyrotropin level and negative results for autoantibodies against Sm, SSA, SSB, Scl-70, Jo-1, centromere, chromatin, ribonucleoprotein, and antineutrophil cytoplasmic antibodies. Erythrocyte sedimentation rate was mildly elevated (30 mm/h). Results of testing for antinuclear antibodies were positive at low titer (1:40, homogenous pattern) with positive dsDNA (5.0 IU/mL; negative if <4.0 IU/mL). Blood cultures were negative for bacterial or fungal growth after 5 days. An echocardiogram revealed pedunculated and mobile aortic valve vegetations. ### OUTPUT:

Nonbacterial thrombotic endocarditis (NBTE) associated with primary antiphospholipid syndrome (APS)

['Coagulation Disorders', 'Hematology', 'Valvular Heart Disease', 'Cardiology', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 42-year-old man was referred for ophthalmologic evaluation after developing blurry vision in the right eye 30 days prior. He had a history of hyperlipidemia, hypertension, and migraine headaches. His medications included atorvastatin, carvedilol, and norethindrone. Dilated-fundus examination of the right eye showed a single cotton-wool spot (indicating local retinal ischemia), with intraretinal hemorrhage in the inferotemporal quadrant. Ultrawide-field imaging showed a cotton-wool spot on the left fundus (Figure 1A, right) and a peripheral arterial occlusion in the right eye (Figure 1A, left), and fluorescein angiographic study of the right eye demonstrated an area of blockage corresponding to intraretinal hemorrhage and venous hyperfluorescence (Figure 1B). The patient was afebrile, with pulse 110 beats/min and blood pressure of 188/99 mm Hg. Auscultation over the heart apex revealed a holosystolic ejection murmur (grade 2/6). Laboratory testing showed normal complete blood cell count and thyrotropin level and negative results for autoantibodies against Sm, SSA, SSB, Scl-70, Jo-1, centromere, chromatin, ribonucleoprotein, and antineutrophil cytoplasmic antibodies. Erythrocyte sedimentation rate was mildly elevated (30 mm/h). Results of testing for antinuclear antibodies were positive at low titer (1:40, homogenous pattern) with positive dsDNA (5.0 IU/mL; negative if <4.0 IU/mL). Blood cultures were negative for bacterial or fungal growth after 5 days. An echocardiogram revealed pedunculated and mobile aortic valve vegetations. ### OUTPUT:

JAMA_FINAL180

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 68-year-old man presented to the clinic with bilateral eye redness and pain for the past 6 months. He had a history of dry eye disease for which he was treated with preservative-free artificial tears. He also noted a medical history of well-controlled HIV with highly active antiretroviral therapy. His last CD 4 lymphocyte count was 750 cells/mm3 with an undetectable viral load. A review of system produced negative results, including absence of weight loss, fevers, headache, joint pain, respiratory symptoms, or skin rash. The patient reported having unprotected sexual contact with multiple male partners in the past few years. On examination, his best-corrected visual acuity was 20/20 OU. Intraocular pressure was 12 mm Hg OD and 14 mm Hg OS. Slitlamp examination demonstrated diffuse scleral injection in both eyes without any scleral thinning. The redness did not blanch after administration of phenylephrine, 10% (Figure 1). Both eyes appeared to be moderately tender to touch. The rest of the anterior segment examination was within normal limits without any evidence of intraocular inflammation. Dilated fundus examination was also unremarkable in both eyes. ### OUTPUT:

Bilateral syphilitic scleritis

['External Eye Disease', 'HIV', 'Infectious Diseases', 'Ophthalmology', 'Sexually Transmitted Infections']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 68-year-old woman presented to the clinic with bilateral eye redness and pain for the past 6 months. She had a history of dry eye disease for which she was treated with preservative-free artificial tears. She also noted a medical history of well-controlled HIV with highly active antiretroviral therapy. Her last CD 4 lymphocyte count was 750 cells/mm3 with an undetectable viral load. A review of system produced negative results, including absence of weight loss, fevers, headache, joint pain, respiratory symptoms, or skin rash. The patient reported having unprotected sexual contact with multiple female partners in the past few years. On examination, her best-corrected visual acuity was 20/20 OU. Intraocular pressure was 12 mm Hg OD and 14 mm Hg OS. Slitlamp examination demonstrated diffuse scleral injection in both eyes without any scleral thinning. The redness did not blanch after administration of phenylephrine, 10% (Figure 1). Both eyes appeared to be moderately tender to touch. The rest of the anterior segment examination was within normal limits without any evidence of intraocular inflammation. Dilated fundus examination was also unremarkable in both eyes. ### OUTPUT:

JAMA_FINAL181

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 50s with a history of nasal-type natural killer (NK)/T-cell lymphoma (diagnosed 2 years prior; treated with pembrolizumab and methotrexate, ifosfamide, etoposide, dexamethasone, and pegaspargase) and chronic pulmonary coccidiomycosis being treated with fluconazole was admitted for fever, hypotension, and rash. Three months prior, pembrolizumab treatment was stopped because of a widespread morbilliform reaction, which had resolved completely 6 to 8 weeks before admission. The new widespread, asymptomatic skin eruption had been ongoing for 1 to 2 weeks and appeared different from her pembrolizumab reaction. A complete blood cell count was notable for a normal white blood cell count of 4100/μL, normal absolute neutrophil count of 2940/μL, chronic normocytic anemia (hemoglobin level of 8.2 g/dL), and chronic thrombocytopenia (platelet count of 62 ×103/μL). Blood culture results showed no growth at 1 week. Serum β-D-glucan, galactomannan, Coccidioides antibody by complement fixation, and immunodiffusion results were negative. Respiratory viral panel and SARS-CoV-2 test results were negative. Total body skin examination findings were notable for widespread, nontender, erythematous patches and thin plaques, some with prominent overlying telangiectases and hyperpigmentation (Figure, A). A punch biopsy of a representative lesion was performed (Figure, B-D). ### OUTPUT:

Intravascular involvement by NK/T-cell lymphoma

['Hematology', 'Oncology', 'Hematologic Cancer', 'Lymphomas', 'Skin Lymphomas']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 50s with a history of nasal-type natural killer (NK)/T-cell lymphoma (diagnosed 2 years prior; treated with pembrolizumab and methotrexate, ifosfamide, etoposide, dexamethasone, and pegaspargase) and chronic pulmonary coccidiomycosis being treated with fluconazole was admitted for fever, hypotension, and rash. Three months prior, pembrolizumab treatment was stopped because of a widespread morbilliform reaction, which had resolved completely 6 to 8 weeks before admission. The new widespread, asymptomatic skin eruption had been ongoing for 1 to 2 weeks and appeared different from his pembrolizumab reaction. A complete blood cell count was notable for a normal white blood cell count of 4100/μL, normal absolute neutrophil count of 2940/μL, chronic normocytic anemia (hemoglobin level of 8.2 g/dL), and chronic thrombocytopenia (platelet count of 62 ×103/μL). Blood culture results showed no growth at 1 week. Serum β-D-glucan, galactomannan, Coccidioides antibody by complement fixation, and immunodiffusion results were negative. Respiratory viral panel and SARS-CoV-2 test results were negative. Total body skin examination findings were notable for widespread, nontender, erythematous patches and thin plaques, some with prominent overlying telangiectases and hyperpigmentation (Figure, A). A punch biopsy of a representative lesion was performed (Figure, B-D). ### OUTPUT:

JAMA_FINAL182

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old man presented with progressive hoarseness and dyspnea over a 2-month period. Fifteen months previously, he had undergone allogeneic stem cell transplant (allo-SCT) with a matched related donor for treatment of fms-like tyrosine kinase (FLT3) internal tandem duplication–mutated acute myeloid leukemia (AML). The patient had been diagnosed with chronic gastrointestinal graft-vs-host disease after a workup for diarrhea. Results of a restaging bone marrow biopsy 2 weeks prior to presentation showed no evidence of leukemia. Physical examination findings revealed no neck masses or abnormalities, but the patient was noted to be severely dysphonic and stridulous. Flexible laryngoscopy findings demonstrated a right vocal fold neoplasm crossing the posterior commissure with associated bilateral vocal fold motion impairment and obstruction of the glottic airway (Figure, A). Awake tracheostomy was performed for airway protection, and biopsy of the neoplasm was obtained via operative microlaryngoscopy (Figure, B). Histologic findings demonstrated diffuse infiltrate of large cells with irregular nuclear contours, vesicular chromatin, and prominent nucleoli (Figure, C). Immunohistochemical stains showed CD33, CD43, and CD117 positivity, with a subset positive for CD7 and myeloperoxidase. Stains were negative for CD3, CD20, and cytokeratin expression. ### OUTPUT:

Extramedullary myeloid sarcoma of the larynx

['Laryngology', 'Otolaryngology', 'Stem Cell Transplantation', 'Hematology', 'Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old woman presented with progressive hoarseness and dyspnea over a 2-month period. Fifteen months previously, she had undergone allogeneic stem cell transplant (allo-SCT) with a matched related donor for treatment of fms-like tyrosine kinase (FLT3) internal tandem duplication–mutated acute myeloid leukemia (AML). The patient had been diagnosed with chronic gastrointestinal graft-vs-host disease after a workup for diarrhea. Results of a restaging bone marrow biopsy 2 weeks prior to presentation showed no evidence of leukemia. Physical examination findings revealed no neck masses or abnormalities, but the patient was noted to be severely dysphonic and stridulous. Flexible laryngoscopy findings demonstrated a right vocal fold neoplasm crossing the posterior commissure with associated bilateral vocal fold motion impairment and obstruction of the glottic airway (Figure, A). Awake tracheostomy was performed for airway protection, and biopsy of the neoplasm was obtained via operative microlaryngoscopy (Figure, B). Histologic findings demonstrated diffuse infiltrate of large cells with irregular nuclear contours, vesicular chromatin, and prominent nucleoli (Figure, C). Immunohistochemical stains showed CD33, CD43, and CD117 positivity, with a subset positive for CD7 and myeloperoxidase. Stains were negative for CD3, CD20, and cytokeratin expression. ### OUTPUT:

JAMA_FINAL183

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 40-year-old man presented with a large left neck mass in the setting of recently treated mixed nonseminomatous germ cell tumor (NSGCT) of the right testicle with metastasis to the retroperitoneal and mediastinal lymph nodes. He was treated with a right radical orchiectomy and 4 cycles of etoposide, ifosfamide, and cisplatin (VIP) chemotherapy with resulting reduction in metastatic tumor burden and normalization of α-fetoprotein and β-human chorionic gonadotropin. The patient’s neck swelling, which initially decreased in size while undergoing chemotherapy, progressively enlarged shortly after concluding treatment. He underwent magnetic resonance imaging and computed tomography of the neck that showed a clearly defined, bulky supraclavicular mass confined to left neck levels 3, 4, and 5 (Figure). ### OUTPUT:

Growing teratoma syndrome

['Oncology', 'Urology', 'Urologic Cancer']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 40-year-old woman presented with a large left neck mass in the setting of recently treated mixed nonseminomatous germ cell tumor (NSGCT) of the right ovary with metastasis to the retroperitoneal and mediastinal lymph nodes. She was treated with a right oophorectomy and 4 cycles of etoposide, ifosfamide, and cisplatin (VIP) chemotherapy with resulting reduction in metastatic tumor burden and normalization of α-fetoprotein and β-human chorionic gonadotropin. The patient’s neck swelling, which initially decreased in size while undergoing chemotherapy, progressively enlarged shortly after concluding treatment. She underwent magnetic resonance imaging and computed tomography of the neck that showed a clearly defined, bulky supraclavicular mass confined to left neck levels 3, 4, and 5 (Figure). ### OUTPUT:

JAMA_FINAL184

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 14-year-old boy was referred to us because of ocular and periocular pain with photophobia in his right eye for the last 5 days. Aside from atopic dermatitis, his medical history was unremarkable. Best-corrected visual acuity was 20/20 OU. Slitlamp examination of the right eye disclosed conjunctival hyperemia and ciliary congestion, anterior chamber flare 2+, and a few nongranulomatous keratic precipitates; the left anterior segment was quiet. Intraocular pressure was 15 mm Hg OU. Pupillary light responses were normal. Dilated fundus examination revealed 1+ of vitritis (binocular indirect ophthalmoscopy score) in the right eye and swelling of the optic disc in both eyes, to a greater extent in the right eye (Figure, A). Routine blood tests, including full blood cell count, plasma glucose levels, liver function test, and kidney function test, were performed on the same day and showed a serum creatinine level of 1.57 mg/dL (reference range: 0.5-1.0 mg/dL; to convert to micromoles per liter, multiply by 88.4). Antibodies anti–Treponema pallidum were tested and the results were negative. ### OUTPUT:

Tubulointerstitial nephritis and uveitis syndrome

['Nephrology', 'Pediatrics', 'Intraocular Inflammation', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 14-year-old girl was referred to us because of ocular and periocular pain with photophobia in her right eye for the last 5 days. Aside from atopic dermatitis, her medical history was unremarkable. Best-corrected visual acuity was 20/20 OU. Slitlamp examination of the right eye disclosed conjunctival hyperemia and ciliary congestion, anterior chamber flare 2+, and a few nongranulomatous keratic precipitates; the left anterior segment was quiet. Intraocular pressure was 15 mm Hg OU. Pupillary light responses were normal. Dilated fundus examination revealed 1+ of vitritis (binocular indirect ophthalmoscopy score) in the right eye and swelling of the optic disc in both eyes, to a greater extent in the right eye (Figure, A). Routine blood tests, including full blood cell count, plasma glucose levels, liver function test, and kidney function test, were performed on the same day and showed a serum creatinine level of 1.57 mg/dL (reference range: 0.5-1.0 mg/dL; to convert to micromoles per liter, multiply by 88.4). Antibodies anti–Treponema pallidum were tested and the results were negative. ### OUTPUT:

JAMA_FINAL185

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her mid-60s, who was in remission following successful combination chemotherapy for Burkitt lymphoma 8 years previously, presented with dyspnea, fatigue, general malaise, and presyncope. On examination, she was normotensive, afebrile, and clinically euvolemic. Laboratory testing showed a hemoglobin level of 12.1 g/dL (to convert to grams per liter, multiply by 10), white blood cell count of 9900/µL (to convert to ×109 per liter, multiply by 0.001), erythrocyte sedimentation rate of 76 mm/h, lactate dehydrogenase level of 139 U/L (to convert to microkatals per liter, multiply by 0.0167), and normal coagulation profile. Serum immunoglobulin quantitation showed normal immunoglobulin (Ig) G, IgA, and IgM levels of 1590 mg/L, 303 mg/L, and 94 mg/L, respectively (to convert to grams per liter, multiply by 0.01). Blood culture findings were negative. Transthoracic and transesophageal echocardiography (Figure 1 and Video) showed a large echogenic mass on the inferior aspect of the interatrial septum with infiltration of the coronary sinus, anterior mitral valve annulus, and aortic root. The mass protruded into the left ventricular outflow tract without causing valve obstruction. Cardiac magnetic resonance imaging confirmed a bilobed interatrial mass measuring 5.6 × 3.1 × 3.8 cm with patchy late gadolinium enhancement of the lesion. Contrast-enhanced computed tomography showed a left hilar mass encasing the left upper lobe bronchus with extension into the left main pulmonary artery, a nodular soft tissue lesion along the anterior nasal septum, and no abdominal or pelvic disease. Magnetic resonance imaging of the brain showed a left paraclinoid mass lesion consistent with a meningioma and right Meckel cave lesions. ### OUTPUT:

Biatrial intracardiac mass and multiple systemic lesions secondary to IgG4-related disease

['Cardiology', 'Oncology', 'Hematologic Cancer', 'Lymphomas']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his mid-60s, who was in remission following successful combination chemotherapy for Burkitt lymphoma 8 years previously, presented with dyspnea, fatigue, general malaise, and presyncope. On examination, he was normotensive, afebrile, and clinically euvolemic. Laboratory testing showed a hemoglobin level of 12.1 g/dL (to convert to grams per liter, multiply by 10), white blood cell count of 9900/µL (to convert to ×109 per liter, multiply by 0.001), erythrocyte sedimentation rate of 76 mm/h, lactate dehydrogenase level of 139 U/L (to convert to microkatals per liter, multiply by 0.0167), and normal coagulation profile. Serum immunoglobulin quantitation showed normal immunoglobulin (Ig) G, IgA, and IgM levels of 1590 mg/L, 303 mg/L, and 94 mg/L, respectively (to convert to grams per liter, multiply by 0.01). Blood culture findings were negative. Transthoracic and transesophageal echocardiography (Figure 1 and Video) showed a large echogenic mass on the inferior aspect of the interatrial septum with infiltration of the coronary sinus, anterior mitral valve annulus, and aortic root. The mass protruded into the left ventricular outflow tract without causing valve obstruction. Cardiac magnetic resonance imaging confirmed a bilobed interatrial mass measuring 5.6 × 3.1 × 3.8 cm with patchy late gadolinium enhancement of the lesion. Contrast-enhanced computed tomography showed a left hilar mass encasing the left upper lobe bronchus with extension into the left main pulmonary artery, a nodular soft tissue lesion along the anterior nasal septum, and no abdominal or pelvic disease. Magnetic resonance imaging of the brain showed a left paraclinoid mass lesion consistent with a meningioma and right Meckel cave lesions. ### OUTPUT:

JAMA_FINAL186

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old woman, with dyslipidemia, presented to the emergency department with sudden vision loss in the right eye. Visual acuity was 20/40 OD and 20/20 OS. Anterior segment, tonometry, and pupillary light reflex were unremarkable. Ophthalmoscopy of the right eye showed discretely blurred optic disc margins, tortuous and dilated retinal veins, and intraretinal hemorrhages in all quadrants; the left eye was unremarkable. An optical coherence tomography (OCT) scan showed a cystoid macular edema (CME) in the right eye; the left was unremarkable. Retinal nerve fiber layer thickness was 133 μm OD and 82 μm OS (reference value, 95.4 ± 10.48 μm).1 A fluorescein angiography was scheduled. One week later, the patient returned to our department due to multiple episodes of amaurosis fugax in left eye. By that time, ophthalmoscopy disclosed a mild optic disc swelling, tortuous venous vessels, and retinal hemorrhages bilaterally (Figure 1). The OCT scan showed a CME spontaneous resolution in the right eye while the left eye was unremarkable. Fluorescein angiography revealed a slight delay in venous filling but no capillary nonperfusion areas. These features were compatible with bilateral nonischemic central retinal vein occlusion (CRVO), with spontaneous reperfusion in the right eye. ### OUTPUT:

Occult tumor presenting with bilateral CRVO

['Coagulation Disorders', 'Hematology', 'Oncology', 'Retinal Disorders', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old man, with dyslipidemia, presented to the emergency department with sudden vision loss in the right eye. Visual acuity was 20/40 OD and 20/20 OS. Anterior segment, tonometry, and pupillary light reflex were unremarkable. Ophthalmoscopy of the right eye showed discretely blurred optic disc margins, tortuous and dilated retinal veins, and intraretinal hemorrhages in all quadrants; the left eye was unremarkable. An optical coherence tomography (OCT) scan showed a cystoid macular edema (CME) in the right eye; the left was unremarkable. Retinal nerve fiber layer thickness was 133 μm OD and 82 μm OS (reference value, 95.4 ± 10.48 μm).1 A fluorescein angiography was scheduled. One week later, the patient returned to our department due to multiple episodes of amaurosis fugax in left eye. By that time, ophthalmoscopy disclosed a mild optic disc swelling, tortuous venous vessels, and retinal hemorrhages bilaterally (Figure 1). The OCT scan showed a CME spontaneous resolution in the right eye while the left eye was unremarkable. Fluorescein angiography revealed a slight delay in venous filling but no capillary nonperfusion areas. These features were compatible with bilateral nonischemic central retinal vein occlusion (CRVO), with spontaneous reperfusion in the right eye. ### OUTPUT:

JAMA_FINAL187

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 13-year-old male presented to the pediatric otolaryngology clinic with a 2-year history of a right neck mass that had slowly increased in size. He denied any associated symptoms of pain, fevers, chills, malaise, night sweats, unintentional weight loss, prior history of neck masses, recent upper respiratory tract infections, or skin lesions. He was the product of a full-term pregnancy with up-to-date immunizations. Physical examination revealed a 2.5-cm firm, ovoid, mobile, and nontender mass at the apex of the posterior triangle of the right neck without any associated overlying skin changes. The remainder of the head and neck examination was unremarkable. Doppler ultrasonography revealed a 1.9 × 1.8 × 0.9-cm hypoechoic mass, and subsequent fine-needle aspirates demonstrated cells with elongated nuclei and eccentric blue cytoplasm in a background of myxoid stroma. The mass was excised in entirety without issue. At the time of surgery, the deep surface of the mass was found to be adherent to the sternocleidomastoid muscle. The lesion was resected with a cuff of muscle and sent for permanent histopathological examination. This revealed proliferation of bland spindle cells with plump nuclei and eosinophilic cytoplasm arranged as loose fascicles in a background of myxoid stroma (Figure 1). These cells were positive for mucin 4 (MUC4), epithelial membrane antigen (EMA), and transducing-like enhancer of split 1 (TLE1) immunohistochemical stains. Fluorescence in situ hybridization (FISH) revealed a positive FUS (16p11) gene rearrangement. ### OUTPUT:

Low-grade fibromyxoid sarcoma

['Adolescent Medicine', 'Otolaryngology', 'Pediatrics', 'Surgery', 'Head and Neck Surgery']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 13-year-old female presented to the pediatric otolaryngology clinic with a 2-year history of a right neck mass that had slowly increased in size. She denied any associated symptoms of pain, fevers, chills, malaise, night sweats, unintentional weight loss, prior history of neck masses, recent upper respiratory tract infections, or skin lesions. She was the product of a full-term pregnancy with up-to-date immunizations. Physical examination revealed a 2.5-cm firm, ovoid, mobile, and nontender mass at the apex of the posterior triangle of the right neck without any associated overlying skin changes. The remainder of the head and neck examination was unremarkable. Doppler ultrasonography revealed a 1.9 × 1.8 × 0.9-cm hypoechoic mass, and subsequent fine-needle aspirates demonstrated cells with elongated nuclei and eccentric blue cytoplasm in a background of myxoid stroma. The mass was excised in entirety without issue. At the time of surgery, the deep surface of the mass was found to be adherent to the sternocleidomastoid muscle. The lesion was resected with a cuff of muscle and sent for permanent histopathological examination. This revealed proliferation of bland spindle cells with plump nuclei and eosinophilic cytoplasm arranged as loose fascicles in a background of myxoid stroma (Figure 1). These cells were positive for mucin 4 (MUC4), epithelial membrane antigen (EMA), and transducing-like enhancer of split 1 (TLE1) immunohistochemical stains. Fluorescence in situ hybridization (FISH) revealed a positive FUS (16p11) gene rearrangement. ### OUTPUT:

JAMA_FINAL188

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 45-year-old woman was referred to the medical retina service for evaluation of bilateral macular atrophy noted by her general ophthalmologist. Medical history was positive for bilateral sensorineural hearing loss with cochlear origin as determined by an otolaryngologist and headache since age 35 years. She had no history of longer-term use of medications. There was no family history of hearing and vision loss in all immediate family members. Her best-corrected visual acuity was 20/20 OD and 20/63 OS. Her pupils were round and reactive. The anterior segment was unremarkable. Fundus examination confirmed the presence of bilateral macular atrophy. Fundus autofluorescence revealed a fairly symmetric loss of autofluorescence in the macula and in the regions surrounding the optic disc (Figure). In proximity of these areas of reduced autofluorescence, a speckled fundus autofluorescence pattern of alternating spots of increased and decreased autofluorescence was also noted. Optical coherence tomography displayed the presence of a bilateral atrophy of the outer retina and retinal pigment epithelium (Figure). The patient’s family underwent a complete ophthalmologic evaluation, which did not display any alteration. ### OUTPUT:

Mitochondrial encephalopathy with lactic acidosis and strokelike episodes–related syndrome

['Dermatology', 'Pediatrics', 'Otolaryngology', 'Audiology and Hearing', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 45-year-old man was referred to the medical retina service for evaluation of bilateral macular atrophy noted by his general ophthalmologist. Medical history was positive for bilateral sensorineural hearing loss with cochlear origin as determined by an otolaryngologist and headache since age 35 years. He had no history of longer-term use of medications. There was no family history of hearing and vision loss in all immediate family members. His best-corrected visual acuity was 20/20 OD and 20/63 OS. His pupils were round and reactive. The anterior segment was unremarkable. Fundus examination confirmed the presence of bilateral macular atrophy. Fundus autofluorescence revealed a fairly symmetric loss of autofluorescence in the macula and in the regions surrounding the optic disc (Figure). In proximity of these areas of reduced autofluorescence, a speckled fundus autofluorescence pattern of alternating spots of increased and decreased autofluorescence was also noted. Optical coherence tomography displayed the presence of a bilateral atrophy of the outer retina and retinal pigment epithelium (Figure). The patient’s family underwent a complete ophthalmologic evaluation, which did not display any alteration. ### OUTPUT:

JAMA_FINAL189

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A school-aged boy experienced generalized erythematous rashes for 4 years. Skin examination showed ichthyosiform brownish plaques on his lower extremities and multiple erythematous confluent papules and plaques on his trunk and face (Figure, A and B). Topical steroid and pimecrolimus were administered, but their effects were limited. In addition, painful distal and proximal interphalangeal joints were noted for 2 years, and the patient could not clench his fists. Uveitis in both eyes was also diagnosed by an ophthalmologist. Microscopic examination of his hair showed no trichorrhexis invaginata or trichorrhexis nodosa. A skin biopsy specimen was obtained and submitted for further histopathologic analysis (Figure, C and D). ### OUTPUT:

Blau syndrome

['Dermatology', 'Ophthalmology', 'Rheumatology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Blau syndrome. Case report: A school-aged girl experienced generalized erythematous rashes for 4 years. Skin examination showed ichthyosiform brownish plaques on her lower extremities and multiple erythematous confluent papules and plaques on her trunk and face (Figure, A and B). Topical steroid and pimecrolimus were administered, but their effects were limited. In addition, painful distal and proximal interphalangeal joints were noted for 2 years, and the patient could not clench her fists. Uveitis in both eyes was also diagnosed by an ophthalmologist. Microscopic examination of her hair showed no trichorrhexis invaginata or trichorrhexis nodosa. A skin biopsy specimen was obtained and submitted for further histopathologic analysis (Figure, C and D). ### OUTPUT:

JAMA_FINAL190

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 70-year-old woman with an ocular history of primary open-angle glaucoma on latanoprost, bilateral trabeculectomies, and argon laser trabeculoplasties presented with several months of worsening vision in the left eye. On examination, her best-corrected distance visual acuity was 20/40 OD and 20/60 OS (baseline 20/40 OU). Pupils were equally round and reactive, without afferent pupillary defect. Findings of Amsler grid testing were notable for a small area of distortion inferiorly in the left eye. Intraocular pressures (IOPs) were 13 mm Hg in both eyes. Findings of anterior segment examination were unremarkable. Findings of dilated fundus examination were notable for cup-disc ratio of 0.9 in the right eye and 0.85 in the left eye with temporal thinning, stable from prior, and new intraretinal thickening in the left eye. Optical coherence tomography (OCT) imaging of the left eye revealed schiticlike separation of the outer plexiform and outer nuclear layers extending from the temporal edge of the optic nerve head to the fovea (Figure 1A), continuous with the peripapillary nerve sheath. ### OUTPUT:

Macular retinoschisis in the setting of glaucomatous optic atrophy

['Macular Diseases', 'Ophthalmology', 'Retinal Disorders', 'Glaucoma', 'Ophthalmic Imaging']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 70-year-old man with an ocular history of primary open-angle glaucoma on latanoprost, bilateral trabeculectomies, and argon laser trabeculoplasties presented with several months of worsening vision in the left eye. On examination, his best-corrected distance visual acuity was 20/40 OD and 20/60 OS (baseline 20/40 OU). Pupils were equally round and reactive, without afferent pupillary defect. Findings of Amsler grid testing were notable for a small area of distortion inferiorly in the left eye. Intraocular pressures (IOPs) were 13 mm Hg in both eyes. Findings of anterior segment examination were unremarkable. Findings of dilated fundus examination were notable for cup-disc ratio of 0.9 in the right eye and 0.85 in the left eye with temporal thinning, stable from prior, and new intraretinal thickening in the left eye. Optical coherence tomography (OCT) imaging of the left eye revealed schiticlike separation of the outer plexiform and outer nuclear layers extending from the temporal edge of the optic nerve head to the fovea (Figure 1A), continuous with the peripapillary nerve sheath. ### OUTPUT:

JAMA_FINAL191

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 20s with a history of daily soft contact lens (CL) wear was referred by her local ophthalmologist for a recalcitrant central corneal ulcer in her left eye. She had no history of eye trauma, did not sleep in her CLs, and stopped using CLs at symptom onset. Of note, she had recently been swimming in a freshwater lake prior to the onset of the ulcer. She was initially treated with topical besifloxacin and followed up daily. She appeared to improve clinically with resolution of her epithelial defect after 3 days, and topical loteprednol was added. Results of initial corneal cultures were negative. One week later, she presented with worsening pain and vision, which prompted referral to our cornea clinic where, 2 weeks after her initial presentation, her best-corrected visual acuity was 20/20 OD and 20/150 OS. Left-eye examination demonstrated diffuse microcystic corneal edema and stromal thickening with no Descemet membrane folds (Figure 1A). A 2 × 2-mm stromal opacity was noted paracentrally with no epithelial defects. The anterior chamber demonstrated 1+ cell. Intraocular pressure was 17 mm Hg OS. Corneal cultures for bacteria, fungi, and acanthamoeba were repeated, and in vivo confocal microscopy (IVCM) was performed on the stromal infiltrate (Figure 1B). After reviewing the IVCM images, what empirical treatment would you recommend while awaiting the results of the repeated corneal cultures? ### OUTPUT:

Purpureocillium lilacinum keratitis confirmed by culture growth 21 days later

['Cornea', 'Infectious Diseases', 'Ophthalmology', 'Emergency Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 20s with a history of daily soft contact lens (CL) wear was referred by his local ophthalmologist for a recalcitrant central corneal ulcer in his left eye. He had no history of eye trauma, did not sleep in his CLs, and stopped using CLs at symptom onset. Of note, he had recently been swimming in a freshwater lake prior to the onset of the ulcer. He was initially treated with topical besifloxacin and followed up daily. He appeared to improve clinically with resolution of his epithelial defect after 3 days, and topical loteprednol was added. Results of initial corneal cultures were negative. One week later, he presented with worsening pain and vision, which prompted referral to our cornea clinic where, 2 weeks after his initial presentation, his best-corrected visual acuity was 20/20 OD and 20/150 OS. Left-eye examination demonstrated diffuse microcystic corneal edema and stromal thickening with no Descemet membrane folds (Figure 1A). A 2 × 2-mm stromal opacity was noted paracentrally with no epithelial defects. The anterior chamber demonstrated 1+ cell. Intraocular pressure was 17 mm Hg OS. Corneal cultures for bacteria, fungi, and acanthamoeba were repeated, and in vivo confocal microscopy (IVCM) was performed on the stromal infiltrate (Figure 1B). After reviewing the IVCM images, what empirical treatment would you recommend while awaiting the results of the repeated corneal cultures? ### OUTPUT:

JAMA_FINAL192

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 53-year-old man received a diagnosis of stage IV melanoma with metastatic disease to the spine and brain 3 months before presentation. Four weeks following receipt of immunotherapy with ipilimumab and nivolumab, he developed acute abdominal pain in the setting of a rapidly rising lactic acid dehydrogenase levels, prompting hospital admission. Imaging results showed mild disease progression (new ascites and periportal metabolic lymph node). Splenic infarct and portal/splenic vein thrombi were identified as etiologies of his acute pain and were presumed to be secondary to hypercoagulable state of malignancy. Over the next 3 days, he had rising serum creatinine (sCr) levels (baseline, approximately 1 mg/dL [to convert to μmol/L, multiply by 88.4]). The initial workup included ultrasonography and urinalysis. Ultrasonography results showed abnormal intraparenchymal flow to both kidneys without evidence of kidney artery stenosis. Urine studies were consistent with prerenal etiology, while the presence of casts suggested acute tubular necrosis. Nephrotoxic medications (omeprazole/pantoprazole) were discontinued. The top differential diagnoses at this juncture included contrast-induced nephropathy or immune checkpoint inhibitor (ICI)–induced acute interstitial nephritis, and empirical high dose steroids were prescribed. Despite observation and steroid treatment, his sCr levels continued to increase over the next 5 days, peaking at 5.8 mg/dL, and the patient progressed into anuric kidney failure, requiring hemodialysis. This prompted a kidney biopsy for definitive diagnosis (Figure). One week later, he received encorafenib, a BRAF inhibitor.1 Two weeks later, the patient’s kidney function began to improve, and hemodialysis was discontinued. He continued to show gradual improvement, with a return to near baseline kidney function (sCr level, 1.3 mg/dL) approximately 6 weeks after treatment initiation. ### OUTPUT:

Acute tubular necrosis secondary to kidney melanoma metastasis

['Nephrology', 'Melanoma', 'Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 53-year-old woman received a diagnosis of stage IV melanoma with metastatic disease to the spine and brain 3 months before presentation. Four weeks following receipt of immunotherapy with ipilimumab and nivolumab, she developed acute abdominal pain in the setting of a rapidly rising lactic acid dehydrogenase levels, prompting hospital admission. Imaging results showed mild disease progression (new ascites and periportal metabolic lymph node). Splenic infarct and portal/splenic vein thrombi were identified as etiologies of her acute pain and were presumed to be secondary to hypercoagulable state of malignancy. Over the next 3 days, she had rising serum creatinine (sCr) levels (baseline, approximately 1 mg/dL [to convert to μmol/L, multiply by 88.4]). The initial workup included ultrasonography and urinalysis. Ultrasonography results showed abnormal intraparenchymal flow to both kidneys without evidence of kidney artery stenosis. Urine studies were consistent with prerenal etiology, while the presence of casts suggested acute tubular necrosis. Nephrotoxic medications (omeprazole/pantoprazole) were discontinued. The top differential diagnoses at this juncture included contrast-induced nephropathy or immune checkpoint inhibitor (ICI)–induced acute interstitial nephritis, and empirical high dose steroids were prescribed. Despite observation and steroid treatment, her sCr levels continued to increase over the next 5 days, peaking at 5.8 mg/dL, and the patient progressed into anuric kidney failure, requiring hemodialysis. This prompted a kidney biopsy for definitive diagnosis (Figure). One week later, she received encorafenib, a BRAF inhibitor. Two weeks later, the patient’s kidney function began to improve, and hemodialysis was discontinued. She continued to show gradual improvement, with a return to near baseline kidney function (sCr level, 1.3 mg/dL) approximately 6 weeks after treatment initiation. ### OUTPUT:

JAMA_FINAL193

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 71-year-old man with a history of rheumatoid arthritis and type 2 diabetes presented to the otolaryngology team with 6 weeks’ history of pain and ulcers in the pharynx. He also complained of nasal regurgitation. He denied having any systemic symptoms. He took linagliptin, valsartan, and 15 mg of methotrexate weekly. He was a nonsmoker and consumed very little alcohol. Clinical examination including flexible nasendoscopy revealed multiple shallow ulcers on the posterior wall of the nasopharynx. There was a large defect involving the entire soft palate on the left. There was no obvious mass or any exophytic lesion. The edges of the soft palate defect were smooth and clean (Figure 1). There were no cranial nerve palsies. There was no cervical, axillary, or inguinal lymphadenopathy. Findings of the remaining head and neck examinations were normal. ### OUTPUT:

EBV-positive mucocutaneous ulcer

['Diabetes', 'Head and Neck Surgery', 'Dental Medicine', 'Otolaryngology', 'Rheumatoid Arthritis']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 71-year-old woman with a history of rheumatoid arthritis and type 2 diabetes presented to the otolaryngology team with 6 weeks’ history of pain and ulcers in the pharynx. She also complained of nasal regurgitation. She denied having any systemic symptoms. She took linagliptin, valsartan, and 15 mg of methotrexate weekly. She was a nonsmoker and consumed very little alcohol. Clinical examination including flexible nasendoscopy revealed multiple shallow ulcers on the posterior wall of the nasopharynx. There was a large defect involving the entire soft palate on the left. There was no obvious mass or any exophytic lesion. The edges of the soft palate defect were smooth and clean (Figure 1). There were no cranial nerve palsies. There was no cervical, axillary, or inguinal lymphadenopathy. Findings of the remaining head and neck examinations were normal. ### OUTPUT:

JAMA_FINAL194

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their early 20s with no medical history or previous symptoms presented for severe frontal headaches and progressive blurred vision in the left eye more than the right eye for several weeks. No localizing signs were documented on neurologic examination. Magnetic resonance imaging (MRI) of the brain with and without contrast, magnetic resonance angiography of the head, and magnetic resonance venography of the head were obtained and were unremarkable. The result of a lumbar puncture showed 101 white blood cells per high-power field (75% lymphocytes). Results of syphilis serologic tests were negative. The patient was discharged with suspected viral meningitis. At a follow-up visit in an ophthalmology clinic 1 week after discharge, visual acuity was 20/25 OD and counting fingers OS. There was no afferent pupillary defect, and an anterior segment examination was within normal limits. A dilated fundus examination showed numerous bilateral creamy-yellow lesions in the peripheral retina with discrete nummular lesions in the posterior pole (Figure 1A). Fundus autofluorescence showed focal areas of hypoautofluorescence with surrounding hyperautofluorescence in both eyes (Figure 1B). The patient continued to report severe and progressive headaches along with blurred vision. A review of systems was otherwise unremarkable. ### OUTPUT:

Acute posterior multifocal placoid pigment epitheliopathy

['Neuro-ophthalmology', 'Neurology', 'Choroidal Disorders', 'Ophthalmology', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their early 20s with no medical history or previous symptoms presented for severe frontal headaches and progressive blurred vision in the left eye more than the right eye for several weeks. No localizing signs were documented on neurologic examination. Magnetic resonance imaging (MRI) of the brain with and without contrast, magnetic resonance angiography of the head, and magnetic resonance venography of the head were obtained and were unremarkable. The result of a lumbar puncture showed 101 white blood cells per high-power field (75% lymphocytes). Results of syphilis serologic tests were negative. The patient was discharged with suspected viral meningitis. At a follow-up visit in an ophthalmology clinic 1 week after discharge, visual acuity was 20/25 OD and counting fingers OS. There was no afferent pupillary defect, and an anterior segment examination was within normal limits. A dilated fundus examination showed numerous bilateral creamy-yellow lesions in the peripheral retina with discrete nummular lesions in the posterior pole (Figure 1A). Fundus autofluorescence showed focal areas of hypoautofluorescence with surrounding hyperautofluorescence in both eyes (Figure 1B). The patient continued to report severe and progressive headaches along with blurred vision. A review of systems was otherwise unremarkable. ### OUTPUT:

JAMA_FINAL195

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 70s was referred to the dermatology department by the rheumatology department with concerns for vasculitis of the bilateral lower legs. She had been healthy until 6 years earlier when she had suddenly developed peripheral neuropathy, with subsequent workup revealing a diagnosis of immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance. Her symptoms had rapidly progressed during the past few months. In addition to worsening neuropathy, she had developed fatigue, weight loss, and sudden altered mental status. An ischemic stroke was identified. The patient was hospitalized, and extensive diagnostic examinations and procedures were completed. A lymphoproliferative disorder with plasmocytic differentiation was detected in a bone marrow biopsy specimen, which together with the monoclonal IgM paraproteinemia was consistent with Waldenström macroglobulinemia (WM). Weeks later, the patient developed an asymptomatic rash of her lower legs. A physical examination revealed several bright red, nonblanchable, pinpoint macules of the bilateral lower legs (Figure, A). An antinuclear antibody test result was positive (titer 1:320, diffuse pattern). Other laboratory testing procedures (ie, complete blood cell count, comprehensive metabolic panel, antineutrophil cytoplasmic antibody, anti-Sjogren syndrome [SS]-A and SS-B, anti–double-stranded DNA, complement [C]3 and C4, homocysteine, β-2-glycoprotein, anticardiolipin, lupus anticoagulant, and vitamin C) returned normal. A punch biopsy of the right lower leg was performed for further diagnostic evaluation (Figure, B-D). ### OUTPUT:

Cutaneous macroglobulinosis

['Rheumatology', 'Neurology', 'Neuromuscular Diseases', 'Neuropathy', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 70s was referred to the dermatology department by the rheumatology department with concerns for vasculitis of the bilateral lower legs. He had been healthy until 6 years earlier when he had suddenly developed peripheral neuropathy, with subsequent workup revealing a diagnosis of immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance. His symptoms had rapidly progressed during the past few months. In addition to worsening neuropathy, he had developed fatigue, weight loss, and sudden altered mental status. An ischemic stroke was identified. The patient was hospitalized, and extensive diagnostic examinations and procedures were completed. A lymphoproliferative disorder with plasmocytic differentiation was detected in a bone marrow biopsy specimen, which together with the monoclonal IgM paraproteinemia was consistent with Waldenström macroglobulinemia (WM). Weeks later, the patient developed an asymptomatic rash of his lower legs. A physical examination revealed several bright red, nonblanchable, pinpoint macules of the bilateral lower legs (Figure, A). An antinuclear antibody test result was positive (titer 1:320, diffuse pattern). Other laboratory testing procedures (ie, complete blood cell count, comprehensive metabolic panel, antineutrophil cytoplasmic antibody, anti-Sjogren syndrome [SS]-A and SS-B, anti–double-stranded DNA, complement [C]3 and C4, homocysteine, β-2-glycoprotein, anticardiolipin, lupus anticoagulant, and vitamin C) returned normal. A punch biopsy of the right lower leg was performed for further diagnostic evaluation (Figure, B-D). ### OUTPUT:

JAMA_FINAL196

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his early 70s with a history of permanent atrial fibrillation treated with atrioventricular junction ablation and biventricular pacemaker implantation was hospitalized with decompensated heart failure and acute kidney injury. His history was notable for nonischemic cardiomyopathy with ejection fraction of 40% and idiopathic pulmonary fibrosis, for which he underwent single-lung transplant 9 years prior. Following diuresis and medical optimization, repeated echocardiogram showed a newly depressed ejection fraction (30%). His electrocardiogram (ECG) was notable for alternating QRS morphologies (Figure 1A). The left ventricular (LV) pacing vector was programmed from LV tip to right ventricular (RV) lead ring. During pacemaker threshold testing, a change in QRS morphology was observed as the output was reduced (Figure 1B). Chest radiography revealed severe right pulmonary fibrosis leading to ipsilateral mediastinal shift and pacemaker lead position unchanged from implantation. ### OUTPUT:

Anodal capture

['Rhythm Disorders', 'Cardiology', 'Heart Failure', 'Medical Devices and Equipment']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Anodal capture. Case report: A woman in her early 70s with a history of permanent atrial fibrillation treated with atrioventricular junction ablation and biventricular pacemaker implantation was hospitalized with decompensated heart failure and acute kidney injury. Her history was notable for nonischemic cardiomyopathy with ejection fraction of 40% and idiopathic pulmonary fibrosis, for which she underwent single-lung transplant 9 years prior. Following diuresis and medical optimization, repeated echocardiogram showed a newly depressed ejection fraction (30%). Her electrocardiogram (ECG) was notable for alternating QRS morphologies (Figure 1A). The left ventricular (LV) pacing vector was programmed from LV tip to right ventricular (RV) lead ring. During pacemaker threshold testing, a change in QRS morphology was observed as the output was reduced (Figure 1B). Chest radiography revealed severe right pulmonary fibrosis leading to ipsilateral mediastinal shift and pacemaker lead position unchanged from implantation. ### OUTPUT:

JAMA_FINAL197

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old man with melanoma and a history of papillary thyroid cancer treated with thyroidectomy presented with 1 week of low-grade fevers, myalgias, and proximal muscle weakness. Three months earlier, he underwent digital amputation of his right third finger and began adjuvant nivolumab treatment for stage IIIC acral-lentiginous melanoma. One week later, he developed fevers, myalgias, dark urine, weakness, and difficulty walking. He had no palpitations, chest pain, or shortness of breath. On examination, his blood pressure was 135/86 mm Hg, pulse 78/min, and he was afebrile. He had reduced strength in bilateral proximal shoulders (3/5), elbow flexors/extensors (3/5), and forearm flexors/extensors (4+/5). No rashes were noted. Laboratory studies demonstrated a creatine kinase (CK) level of 111 859 U/L (reference range, 30-220 U/L), CK-MB of 270 ng/mL (reference, <8 ng/mL), and aldolase above 500 U/L (reference, <7.7 U/L). Aspartate aminotransferase level was 1980 U/L (reference range, 15-41 U/L), alanine aminotransferase was 814 U/L (reference range, 14-54 U/L), creatinine was 4.9 mg/dL (reference range, 0.4-1.0 mg/dL) with a previously normal baseline, and potassium was 6.4 mmol/L (reference range, 3.5-5.0 mmol/L). Urinalysis showed 27 red blood cells (reference range, 0-5) and myoglobin above 5000 µg/L (reference, 0 µg/L). Erythrocyte sedimentation rate was 67 mm/h (reference, <20 mm/h) and C-reactive protein was 10.2 mg/dL (reference, ≤0.60 mg/dL). Magnetic resonance imaging (MRI) of the left humerus demonstrated T2 flare most pronounced within the biceps and anterior lateral deltoid muscles (Figure). The patient’s electrocardiogram (ECG) is also shown in the Figure. ### OUTPUT:

Nivolumab-induced myositis with myocarditis

['Cardiology', 'Dermatology', 'Clinical Pharmacy and Pharmacology', 'Melanoma', 'Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old woman with melanoma and a history of papillary thyroid cancer treated with thyroidectomy presented with 1 week of low-grade fevers, myalgias, and proximal muscle weakness. Three months earlier, she underwent digital amputation of her right third finger and began adjuvant nivolumab treatment for stage IIIC acral-lentiginous melanoma. One week later, she developed fevers, myalgias, dark urine, weakness, and difficulty walking. She had no palpitations, chest pain, or shortness of breath. On examination, her blood pressure was 135/86 mm Hg, pulse 78/min, and she was afebrile. She had reduced strength in bilateral proximal shoulders (3/5), elbow flexors/extensors (3/5), and forearm flexors/extensors (4+/5). No rashes were noted. Laboratory studies demonstrated a creatine kinase (CK) level of 111 859 U/L (reference range, 30-220 U/L), CK-MB of 270 ng/mL (reference, <8 ng/mL), and aldolase above 500 U/L (reference, <7.7 U/L). Aspartate aminotransferase level was 1980 U/L (reference range, 15-41 U/L), alanine aminotransferase was 814 U/L (reference range, 14-54 U/L), creatinine was 4.9 mg/dL (reference range, 0.4-1.0 mg/dL) with a previously normal baseline, and potassium was 6.4 mmol/L (reference range, 3.5-5.0 mmol/L). Urinalysis showed 27 red blood cells (reference range, 0-5) and myoglobin above 5000 µg/L (reference, 0 µg/L). Erythrocyte sedimentation rate was 67 mm/h (reference, <20 mm/h) and C-reactive protein was 10.2 mg/dL (reference, ≤0.60 mg/dL). Magnetic resonance imaging (MRI) of the left humerus demonstrated T2 flare most pronounced within the biceps and anterior lateral deltoid muscles (Figure). The patient’s electrocardiogram (ECG) is also shown in the Figure. ### OUTPUT:

JAMA_FINAL198

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old man with a history of hypertensive retinopathy presented with acute-onset, painless vision loss in his right eye accompanied by tinnitus and severe intermittent headaches. His extraocular movements were full, and he had no other neurologic deficits. His visual acuity was 20/400 OD and 20/30 OS, respectively, and his fundi were notable for bilateral optic nerve edema. Results of recent computed tomography and angiography of the head and neck and magnetic resonance imaging of the brain and orbits were reportedly normal, and lumbar puncture revealed an opening pressure of 26 cm H2O (normal range, 6 to 25 cm H2O) with elevated protein. The patient was given acetazolamide and referred to neuro-ophthalmology. On examination by neuro-ophthalmology 4 months later, his visual acuity was 20/50 OD and 20/20 OS. He had an afferent pupillary defect in the right eye, and Humphrey visual fields (24-2) showed binasal inferior defects with a superior defect in the right eye that was considered an artifact of testing. According to the Ishihara color plates test, color vision was full in both eyes. Fundus examination was remarkable for pallor of both optic nerves, more notably in the right eye, without edema (Figure 1). Findings of screening for antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, Bartonella, HIV, tuberculosis (Quantiferon), Treponema pallidum, erythrocyte sedimentation rate, C-reactive protein, and a complete blood cell count were normal. ### OUTPUT:

Primary angiitis of the central nervous system

['Ophthalmology', 'Retinal Disorders', 'Headache', 'Neurology', 'Neuro-ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old woman with a history of hypertensive retinopathy presented with acute-onset, painless vision loss in her right eye accompanied by tinnitus and severe intermittent headaches. Her extraocular movements were full, and she had no other neurologic deficits. Her visual acuity was 20/400 OD and 20/30 OS, respectively, and her fundi were notable for bilateral optic nerve edema. Results of recent computed tomography and angiography of the head and neck and magnetic resonance imaging of the brain and orbits were reportedly normal, and lumbar puncture revealed an opening pressure of 26 cm H2O (normal range, 6 to 25 cm H2O) with elevated protein. The patient was given acetazolamide and referred to neuro-ophthalmology. On examination by neuro-ophthalmology 4 months later, her visual acuity was 20/50 OD and 20/20 OS. She had an afferent pupillary defect in the right eye, and Humphrey visual fields (24-2) showed binasal inferior defects with a superior defect in the right eye that was considered an artifact of testing. According to the Ishihara color plates test, color vision was full in both eyes. Fundus examination was remarkable for pallor of both optic nerves, more notably in the right eye, without edema (Figure 1). Findings of screening for antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, Bartonella, HIV, tuberculosis (Quantiferon), Treponema pallidum, erythrocyte sedimentation rate, C-reactive protein, and a complete blood cell count were normal. ### OUTPUT:

JAMA_FINAL199

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 36-year-old man presented to the emergency department with 3 weeks of generalized weakness and a dry cough. He reported hair loss for 1 month. Medical history was significant for opioid and alcohol use disorders, injection drug use, and chronic HIV infection. He discontinued his antiretroviral therapy 2 years prior to presentation. At that time, his CD4+ cell count was 820/μL and his HIV viral load was undetectable. On presentation, his heart rate was 88/min and regular; blood pressure, 90/58 mm Hg; oxygen saturation, 100% on room air; and respiratory rate, 20/min. He was afebrile. Cardiorespiratory auscultation was deferred because a diagnosis of COVID-19 was considered. He had a faint maculopapular rash on his arms and torso and patchy hair loss on his scalp (Figure). There were no genital lesions or mucosal ulcerations. ### OUTPUT:

“Moth-eaten” alopecia caused by secondary syphilis

['Hair Disorders', 'Sexually Transmitted Infections', 'HIV', 'Infectious Diseases', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 36-year-old woman presented to the emergency department with 3 weeks of generalized weakness and a dry cough. She reported hair loss for 1 month. Medical history was significant for opioid and alcohol use disorders, injection drug use, and chronic HIV infection. She discontinued her antiretroviral therapy 2 years prior to presentation. At that time, her CD4+ cell count was 820/μL and her HIV viral load was undetectable. On presentation, her heart rate was 88/min and regular; blood pressure, 90/58 mm Hg; oxygen saturation, 100% on room air; and respiratory rate, 20/min. She was afebrile. Cardiorespiratory auscultation was deferred because a diagnosis of COVID-19 was considered. She had a faint maculopapular rash on her arms and torso and patchy hair loss on her scalp (Figure). There were no genital lesions or mucosal ulcerations. ### OUTPUT:

JAMA_FINAL200

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 64-year-old woman with a history of hyperlipidemia, hypertension, HIV infection, coronary artery disease, and squamous cell carcinoma of the left mandible treated with composite resection, left neck dissection, and fibula free flap (FFF) reconstruction followed by postoperative radiotherapy presented with sharp, shooting left neck pain. Beginning 5 months after her reconstruction, the patient reported point tenderness on the left jaw, facial swelling, and electric pain with severity of 7 out of 10 in the left neck that occurred with talking or eating. Her postoperative course was complicated by osteoradionecrosis post-tracheostomy, plate removal, and left segmental mandibulectomy. She received regular physical therapy and lymphedema therapy and was seen by Physical Medicine and Rehabilitation, who treated her with onabotulinum toxin A injections; neither provided significant resolution of her symptoms. Review of a computed tomography scan of the head and neck (Figure 1) performed on follow-up 5 years after initial reconstruction demonstrated a long, hyperdense structure in the left submental, submandibular region with accompanying soft-tissue thickening. On further review of prior imaging, this calcification appeared as a new finding in various scans dating back to 5 months after FFF reconstruction compared with preoperative imaging. There was no fluorodeoxyglucose avidity in the area of question on multiple positron emission tomography scans done during this follow-up window. ### OUTPUT:

Ossification of the free flap pedicle

['Facial Plastic Surgery', 'Otolaryngology', 'Head and Neck Reconstruction', 'Pain Medicine', 'Radiation Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Ossification of the free flap pedicle. Case report: A 64-year-old man with a history of hyperlipidemia, hypertension, HIV infection, coronary artery disease, and squamous cell carcinoma of the left mandible treated with composite resection, left neck dissection, and fibula free flap (FFF) reconstruction followed by postoperative radiotherapy presented with sharp, shooting left neck pain. Beginning 5 months after his reconstruction, the patient reported point tenderness on the left jaw, facial swelling, and electric pain with severity of 7 out of 10 in the left neck that occurred with talking or eating. His postoperative course was complicated by osteoradionecrosis post-tracheostomy, plate removal, and left segmental mandibulectomy. He received regular physical therapy and lymphedema therapy and was seen by Physical Medicine and Rehabilitation, who treated him with onabotulinum toxin A injections; neither provided significant resolution of his symptoms. Review of a computed tomography scan of the head and neck (Figure 1) performed on follow-up 5 years after initial reconstruction demonstrated a long, hyperdense structure in the left submental, submandibular region with accompanying soft-tissue thickening. On further review of prior imaging, this calcification appeared as a new finding in various scans dating back to 5 months after FFF reconstruction compared with preoperative imaging. There was no fluorodeoxyglucose avidity in the area of question on multiple positron emission tomography scans done during this follow-up window. ### OUTPUT:

JAMA_FINAL201

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his late 70s with stage IV adenocarcinoma of the lung presented with acute onset of redness, pain, and swelling of both lower limbs. The patient had received 4 cycles of chemotherapy with carboplatin, pemetrexed, and pembrolizumab for progressive disease and was currently in maintenance with pemetrexed-pembrolizumab. The edema appeared 5 days after the patient’s 8th cycle of chemotherapy and evolved into sclerotic plaques. Physical examination revealed ill-defined, erythematoedematous plaques symmetrically distributed along the shins, with areas of induration (Figure, A). The patient remained afebrile and systemically well. Results of laboratory tests showed no elevation of inflammatory markers (normal white blood cell count and C-reactive protein level), with kidney, liver, and heart functions within the normal ranges. Results of venous Doppler ultrasonography imaging of the patient’s legs did not show evidence of deep vein thrombosis. A biopsy specimen was obtained for histopathologic analysis (Figure, B and C). ### OUTPUT:

Pemetrexed-induced inflammatory and sclerotic edema

['Dermatology', 'Oncology', 'Targeted and Immune Therapy', 'Lung Cancer']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her late 70s with stage IV adenocarcinoma of the lung presented with acute onset of redness, pain, and swelling of both lower limbs. The patient had received 4 cycles of chemotherapy with carboplatin, pemetrexed, and pembrolizumab for progressive disease and was currently in maintenance with pemetrexed-pembrolizumab. The edema appeared 5 days after the patient’s 8th cycle of chemotherapy and evolved into sclerotic plaques. Physical examination revealed ill-defined, erythematoedematous plaques symmetrically distributed along the shins, with areas of induration (Figure, A). The patient remained afebrile and systemically well. Results of laboratory tests showed no elevation of inflammatory markers (normal white blood cell count and C-reactive protein level), with kidney, liver, and heart functions within the normal ranges. Results of venous Doppler ultrasonography imaging of the patient’s legs did not show evidence of deep vein thrombosis. A biopsy specimen was obtained for histopathologic analysis (Figure, B and C). ### OUTPUT:

JAMA_FINAL202

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old man presented with multiple progressive ulcers on the right side of his face that had developed over the past 3 months (Figure, A). He had also experienced a burning sensation on the right side of his face, but denied headache, shoulder, or jaw pain and visual disturbance. Neurological examination revealed hypoesthesia of the right side of the face, while cold-warm sensation and motor function were intact. The erythrocyte sedimentation rate was 82 mm per hour (normal value, less than 15 mm per hour) and the serum C–reactive protein concentration was 107 mg/L (normal value, less than 5 mg/L). Chest radiography showed bilateral perihilar infiltrates consistent with pneumonia. About 2 weeks before the ulcerations developed, the patient had been admitted to the hospital for unstable angina, and coronary angiography was performed. Immediately after the angiography, the patient developed left-sided hemiplegia and hemianopsia. Magnetic resonance imaging of the brain revealed an extensive ischemic posterior circulation stroke involving the right occipital lobe, lower cerebellar peduncle, and pontomedullary boundary (Figure, B). ### OUTPUT:

Trigeminal trophic syndrome

['Cerebrovascular Disease', 'Dermatology', 'Neurology', 'Stroke', 'Cerebrovascular Infarction']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old woman presented with multiple progressive ulcers on the right side of her face that had developed over the past 3 months (Figure, A). She had also experienced a burning sensation on the right side of her face, but denied headache, shoulder, or jaw pain and visual disturbance. Neurological examination revealed hypoesthesia of the right side of the face, while cold-warm sensation and motor function were intact. The erythrocyte sedimentation rate was 82 mm per hour (normal value, less than 15 mm per hour) and the serum C–reactive protein concentration was 107 mg/L (normal value, less than 5 mg/L). Chest radiography showed bilateral perihilar infiltrates consistent with pneumonia. About 2 weeks before the ulcerations developed, the patient had been admitted to the hospital for unstable angina, and coronary angiography was performed. Immediately after the angiography, the patient developed left-sided hemiplegia and hemianopsia. Magnetic resonance imaging of the brain revealed an extensive ischemic posterior circulation stroke involving the right occipital lobe, lower cerebellar peduncle, and pontomedullary boundary (Figure, B). ### OUTPUT: