Rheumatology USMLE Practice Questions
Autoimmune and musculoskeletal disorders.
5 free rheumatology practice questions
Pick an answer and check it. After each question you get the same explanation StepGenie students see: the stem decoded clue by clue, the reasoning chain with its infographic, why every wrong option is wrong, and the trap the question was built around. Step 1 questions test mechanism; Step 2 CK questions ask for the next step.
An investigator is evaluating age-related changes in bone metabolism by comparing serum studies and bone biopsy findings in a cohort of women aged 25–35 years with those of women aged 55–65 years. Which of the following bone-related processes is most likely to be increased in the older cohort?
Correct answer · A
Expression of RANK ligand
Decoding the stem
Step-by-step reasoning
Step 1 of 5
Women aged 55–65 are typically postmenopausal, leading to decreased estrogen levels.
Step 2 of 5
Estrogen normally inhibits osteoclasts partly by decreasing RANKL expression on osteoblasts/stromal cells and increasing osteoprotegerin (OPG).
Step 3 of 5
Loss of estrogen removes this inhibition → osteoblasts/stromal cells express more RANKL and less OPG.
Step 4 of 5
RANKL binds RANK on osteoclast precursors → promotes their differentiation and activation.
Step 5 of 5
↑ Osteoclast activity → increased bone resorption → age-related (postmenopausal) osteoporosis in the older cohort.
Why not the others?
B. Demineralization of bone with normal osteoid matrix
This implies osteoporosis vs osteomalacia distinction, but the question asks for a process, not a histologic pattern. Also, both cohorts mineralize normally; the older group has increased resorption, not just ‘demineralization’ as a primary process.
C. Urinary excretion of cyclic AMP
This option implies primary hyperparathyroidism, which causes high PTH → ↑ urinary cAMP, BUT the vignette describes normal aging, not a PTH-secreting adenoma or hypercalcemia syndrome.
D. Activation of fibroblast growth factor receptor 3
This implies achondroplasia, due to activating mutations in FGFR3 affecting endochondral ossification in children, BUT the question is about age-related changes in adults, not congenital dwarfism.
E. Urinary excretion of osteocalcin
Increased osteocalcin excretion suggests high bone turnover in general (e.g., hyperparathyroidism, Paget disease), BUT age-related osteoporosis is more specifically driven by RANKL-mediated osteoclast activation; osteocalcin is not the primary mechanistic hallmark being tested.
F. Production of osteoprotegerin
OPG is a decoy receptor that binds RANKL and inhibits osteoclast activation. Estrogen deficiency actually decreases OPG, BUT the older cohort has more bone resorption, so OPG would not be increased.
Exam trap
Students may overfocus on ‘older women → osteoporosis’ and then jump to broad markers (osteocalcin, demineralization) instead of identifying the specific molecular driver: increased RANKL due to estrogen loss.
The bottom line
Postmenopausal osteoporosis from estrogen loss → ↑ RANKL expression → ↑ osteoclast activity → bone resorption with normal labs and thin trabeculae.
A 32-year-old African American woman comes to the physician with 6 weeks of fatigue and difficulty swallowing. She also reports episodic painful discoloration of her fingers on exposure to cold. She has a 4-year history of smoking one pack of cigarettes daily. She appears younger than her stated age. Physical examination shows smooth, swollen fingers with small white calcifications on the fingertips bilaterally. Which of the following complications is this patient most at risk for developing?
Correct answer · C
Pulmonary hypertension
Decoding the stem
Step-by-step reasoning
- 1
Raynaud phenomenon + smooth, swollen, tight fingers + fingertip calcifications → points to limited cutaneous systemic sclerosis (CREST syndrome).
- 2
CREST stands for Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasias. This patient already shows several components (C, R, E, S).
- 3
Limited systemic sclerosis is characterized by vascular dysfunction and fibrosis, particularly affecting small arteries and arterioles in the lungs.
- 4
Chronic vascular injury and intimal proliferation in pulmonary arteries → pulmonary arterial hypertension (PAH).
- 5
Pulmonary hypertension in systemic sclerosis causes progressive dyspnea, right heart failure, and is a leading cause of mortality → making it the key at-risk complication here.
Why not the others?
A. Liver cirrhosis
This option implies chronic liver disease (e.g., from alcohol, viral hepatitis, NAFLD), which causes portal hypertension and liver failure, BUT the stem focuses on Raynaud, sclerodactyly, calcinosis, and no stigmata of liver disease (jaundice, ascites, spider angiomata) are present.
B. Chronic obstructive pulmonary disease
This option implies smoking-related emphysema/chronic bronchitis with chronic cough, sputum, and airflow obstruction, BUT although she smokes, the key findings are autoimmune connective tissue disease signs, and there are no respiratory symptoms or obstructive lung disease clues given.
D. Glomerular basement membrane disease
This option implies diseases like Goodpasture syndrome or other primary glomerulopathies presenting with hematuria, proteinuria, or nephritic/nephrotic syndrome, BUT the vignette lacks any renal or urinary findings; systemic sclerosis renal disease is typically scleroderma renal crisis (malignant hypertension), not isolated GBM disease.
E. Aortic aneurysm
This option implies cystic medial degeneration (e.g., Marfan) or atherosclerotic disease in older patients, BUT this young woman’s main pathology is small vessel vasculopathy and fibrosis of systemic sclerosis, not large-vessel aortic pathology; no hypertension, connective tissue disorder like Marfan, or syphilis clues are present.
F. Chondrocalcinosis
This option implies pseudogout (calcium pyrophosphate deposition disease) with episodic joint pain and x-ray cartilage calcification, BUT the patient’s calcifications are in the skin of fingertips (calcinosis cutis), not in cartilage, and there are no acute monoarthritis episodes described.
Exam trap
The smoking history and young age might push students toward COPD or aortic disease, but the high-yield constellation of Raynaud + sclerodactyly + calcinosis is classic for limited systemic sclerosis/CREST, whose hallmark serious complication is pulmonary arterial hypertension, not primary smoking-related lung disease.
The bottom line
Limited cutaneous systemic sclerosis (CREST) with Raynaud and sclerodactyly predisposes to pulmonary arterial hypertension, a major cause of mortality.
A 62-year-old woman presents with a 6-month history of progressively worsening pain and stiffness in the fingers of her right hand. The stiffness is most pronounced at the end of the day. She recently retired after working for 28 years as a typist at a data entry firm. Physical examination reveals swelling, joint-line tenderness, and decreased range of motion in the first metacarpophalangeal joint and the distal interphalangeal joints of the right hand. Discrete, hard, mildly tender nodules are palpable over the 2nd and 4th distal interphalangeal joints. Radiographs of the right hand demonstrate narrowing of the interphalangeal joint spaces with subchondral sclerosis and osteophyte formation. Which of the following is the most likely underlying mechanism of this patient's condition?
Correct answer · E
Degenerative disease of the joints
Decoding the stem
Step-by-step reasoning
Step 1 of 6
Age >60 and long history of repetitive joint use (typist) predispose to degenerative joint disease from chronic mechanical stress.
Step 2 of 6
Mechanical “wear and tear” causes articular cartilage degeneration, especially in frequently used joints like DIPs, PIPs, and sometimes MCPs.
Step 3 of 6
Cartilage loss leads to joint-space narrowing and increased load on subchondral bone → subchondral sclerosis and cysts.
Step 4 of 6
Reactive bone formation at joint margins produces osteophytes, which present as hard, bony nodules (Heberden and Bouchard nodes).
Step 5 of 6
Mechanical pain is worse with use and in the evening, differing from inflammatory arthritis (morning stiffness improving with use).
Step 6 of 6
Thus, the underlying mechanism is degenerative disease of the joints consistent with osteoarthritis.
Why not the others?
A. Monosodium urate crystal precipitation in the joints
This option implies gout, which causes sudden, severe, acute monoarticular pain (often 1st MTP) with redness and warmth, BUT this patient has chronic, progressive hand joint disease with osteophytes and evening stiffness, not acute crystal arthritis.
B. Bacterial infection of the joint space
This option implies septic arthritis, which presents with acute onset, severe pain, marked warmth, erythema, systemic signs (fever), and usually a single joint, BUT this patient has a 6‑month chronic course, no systemic symptoms, and radiographic degenerative changes.
C. Autoimmune-mediated cartilage erosion
This option implies rheumatoid arthritis, which typically affects MCPs and PIPs with morning stiffness improving with use, symmetric involvement, and periarticular osteopenia/erosions (not osteophytes), BUT this patient has DIP involvement, evening-predominant pain, and osteophytes—classic for osteoarthritis, not autoimmune erosion.
D. Calcium pyrophosphate dihydrate crystal precipitation in the joints
This option implies pseudogout, which usually affects large joints (classically the knee) with acute inflammatory attacks and shows chondrocalcinosis on imaging, BUT this patient has chronic hand involvement with joint-space narrowing, sclerosis, and osteophytes, not acute large-joint pseudogout.
Exam trap
Students may see hand joints + nodules and reflexively think rheumatoid arthritis or gout. The key discriminator is evening mechanical pain + DIPs + osteophytes, which points to osteoarthritis (degenerative disease), not inflammatory or crystal-mediated arthritis.
The bottom line
Osteoarthritis: degenerative cartilage loss with subchondral sclerosis and osteophytes causing evening joint pain and stiffness in weight-bearing and frequently used joints.
A 27-year-old man presents with a several-day history of bilateral knee pain without any preceding trauma or changes in activity. Two weeks ago, he had an episode of acute diarrhea. Over the past week, he has also developed dysuria and reports intermittent eye irritation with painful blurry vision. He is afebrile. Ocular examination shows conjunctival injection surrounding the iris. Synovial fluid aspiration from the knee demonstrates a white blood cell count of 51,000/µL. Which of the following is the most appropriate treatment for this patient’s condition?
Correct answer · D
Indomethacin
Decoding the stem
Step-by-step reasoning
- 1
Young man with acute, inflammatory arthritis of the knees plus urethritis and conjunctivitis suggests a seronegative spondyloarthropathy rather than degenerative disease.
- 2
History of acute diarrhea 2 weeks prior fits the classic post-GI infection timeline for reactive arthritis (formerly Reiter syndrome).
- 3
The classic triad of reactive arthritis: arthritis (knees), urethritis (dysuria), and conjunctivitis/uveitis (eye irritation, injection) is present here.
- 4
Synovial WBC ~51,000/µL supports an inflammatory process; lack of systemic toxicity and classic triad favors sterile reactive arthritis, not septic arthritis.
- 5
First-line management of reactive arthritis is NSAIDs to control inflammatory joint pain and swelling; indomethacin is a potent NSAID used for this purpose.
- 6
Therefore, Indomethacin is the most appropriate treatment among the options given.
Why not the others?
A. Acetaminophen
This option implies simple analgesia for mild pain, which reduces fever/pain but has minimal anti-inflammatory effect, BUT this patient has a significant inflammatory arthritis (WBC 51,000/µL) requiring NSAID-level anti-inflammatory therapy.
B. Allopurinol
This option implies chronic urate-lowering therapy for gout, which is used for prevention, NOT acute inflammatory episodes, BUT the patient has a post-infectious arthritis with urethritis and conjunctivitis, not recurrent monoarticular gouty flares or hyperuricemia.
C. Colchicine
This option implies treatment of acute gout or familial Mediterranean fever, which typically presents with sudden, severe monoarticular pain (often 1st MTP) and crystal-proven gout, BUT this patient has post-diarrheal, seronegative reactive arthritis with urethritis and ocular findings, not gout.
E. Leflunomide
This option implies disease-modifying therapy for rheumatoid or psoriatic arthritis, which is used for chronic, symmetric polyarthritis or specific spondyloarthropathies, BUT initial management of reactive arthritis is NSAIDs; DMARDs are reserved for persistent or refractory disease, which is not described here.
Exam trap
The triad joint pain + dysuria + eye symptoms after diarrhea points to reactive arthritis, but many students anchor on “joint pain” alone and pick gout or RA drugs like allopurinol, colchicine, or leflunomide. Recognizing the full triad and post-infectious timing is key to choosing NSAIDs as first-line therapy.
The bottom line
Reactive arthritis (HLA-B27 spondyloarthropathy) after diarrhea: triad of arthritis, urethritis, conjunctivitis. First-line treatment is NSAIDs (e.g., indomethacin).
A 45-year-old man presents with a 1-year history of progressive limitation in movement of his right hand. He reports difficulty actively extending the 4th and 5th fingers of his right hand, which has worsened despite stretching exercises. His medical history is significant for type 2 diabetes mellitus managed with metformin. He has worked as a mason for over 20 years. His father had similar symptoms that required surgical treatment. The patient smokes 1 pack of cigarettes daily (25-pack-year history) and drinks 2–3 beers daily. Vital signs are within normal limits. Physical examination shows skin puckering near the proximal palmar flexor crease and several painless nodules along the distal palmar crease. Active and passive extension of the 4th and 5th digits of the right hand is restricted. Which of the following is the most likely underlying mechanism of this patient’s symptoms?
Correct answer · A
Palmar fibromatosis
Decoding the stem
Step-by-step reasoning
Step 1 of 5
Patient has chronic progressive inability to extend 4th/5th digits, indicating a flexion contracture rather than joint pain or acute nerve injury.
Step 2 of 5
Physical exam shows painless nodules and skin puckering over the distal/proximal palmar creases, pointing to disease of the palmar fascia, not joints or tendons.
Step 3 of 5
Dupuytren contracture is due to palmar fibromatosis: fibroblast proliferation and collagen deposition in the palmar aponeurosis causing thickened cords.
Step 4 of 5
Fibrosis of the palmar fascia gradually pulls the ring and little fingers into flexion, limiting both active and passive extension as described.
Step 5 of 5
Association with diabetes, manual labor, smoking, alcohol and positive family history further supports palmar fibromatosis (Dupuytren contracture) as the mechanism.
Why not the others?
B. Osteoarthritis
This option implies degenerative joint disease causing joint pain, stiffness, and bony enlargement (DIP/PIP). BUT this patient has painless palmar nodules and skin puckering with fascial contracture, not joint line tenderness or bony changes.
C. Ganglion cyst
This option implies a fluid-filled cyst arising from a joint capsule or tendon sheath, usually a single smooth mass on the wrist or dorsum of hand. BUT this patient has multiple palmar nodules with a cord-like contracture and skin puckering, not a discrete cystic lesion.
D. Ulnar nerve lesion
This option implies neuropathy causing sensory loss in ulnar distribution and intrinsic hand muscle weakness (clawing). BUT the stem emphasizes palmar nodules, skin puckering, and mechanical restriction of extension without sensory deficits or classic neurologic findings.
E. Tendon sheath tumor
This option implies a localized mass along a tendon sheath (e.g., giant cell tumor of tendon sheath) causing focal swelling and sometimes pain. BUT there is a characteristic pattern of multiple palmar nodules and progressive flexion contracture, which reflects fascial fibromatosis, not a discrete tumor.
F. Tenosynovitis
This option implies inflammation of a tendon sheath, causing acute pain, swelling, warmth, and sometimes triggering. BUT the patient’s course is chronic, painless, and associated with palmar nodules and skin puckering, not inflammatory pain or swelling.
Exam trap
The stem focuses on hand dysfunction and ring/little finger involvement, tempting you to pick ulnar nerve lesion. Careful attention to palmar nodules, skin puckering, painless, progressive contracture points instead to palmar fascia fibromatosis (Dupuytren contracture), not neuropathy or joint disease.
The bottom line
Dupuytren contracture from palmar fibromatosis causes progressive flexion contractures of 4th/5th fingers with palmar nodules and skin puckering.
Source: StepGenie question bank. Questions are written by StepGenie, not taken from NBME or USMLE materials, and are chosen for this page by how students actually performed on them (first-attempt accuracy on StepGenie). Selection last refreshed September 5, 2026.
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About Rheumatology
Comprehensive review of rheumatoid arthritis, lupus, vasculitis, crystal arthropathies, and connective tissue diseases. Learn the approach to joint pain and interpretation of serologic markers.
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Are the rheumatology practice questions on this page free?
Yes. The 5 questions above come from StepGenie's question bank and can be answered here without an account, with the full explanation shown after each one. From the link under the set you can try three more Rheumatology questions in the dashboard preview, also without an account; a free account is what lets you choose the system and keep going.