USMLE Step 2 CK rheumatology & musculoskeletal questions

Symmetric small-joint polyarthritis involving the MCP and PIP joints with sparing of the DIP joints, accompanied by prolonged morning stiffness (>1 hour) that improves with activity, is the classic presentation of rheumatoid arthritis. This pattern reflects inflammatory synovitis rather than the mechanical joint pain of osteoarthritis. The DIP-sparing pattern and symmetry help distinguish it from osteoarthritis and psoriatic arthritis. Diagnosis is supported clinically and confirmed with serologic and imaging studies.

• A. Osteoarthritis typically involves DIP and first CMC joints, causes brief morning stiffness (<30 minutes), and worsens with activity.
• C. Reactive arthritis is typically asymmetric and oligoarticular, often following a GI or GU infection, with lower extremity predominance.
• D. Lupus arthritis is usually non-erosive and migratory, and would be expected with other systemic features such as rash or serositis.
• E. Psoriatic arthritis typically involves DIP joints and is associated with nail pitting or psoriatic skin lesions, which are absent here.

Anti-cyclic citrullinated peptide (anti-CCP) antibody has a specificity of approximately 95% for rheumatoid arthritis, substantially higher than rheumatoid factor, which can be positive in other autoimmune diseases, chronic infections, and even healthy older adults. Anti-CCP antibodies may also appear years before clinical onset and are associated with more erosive disease. Combining RF and anti-CCP testing increases diagnostic confidence and is incorporated into the ACR/EULAR classification criteria for RA.

• A. ESR is a nonspecific marker of inflammation used to assess disease activity, not to establish diagnostic specificity.
• C. CRP, like ESR, reflects general inflammation and does not distinguish RA from other inflammatory conditions.
• D. Anti-dsDNA is specific for systemic lupus erythematosus, not rheumatoid arthritis.
• E. ANA is useful for screening systemic lupus erythematosus but is nonspecific and not primarily used to confirm RA.

Methotrexate is the first-line DMARD for most patients with rheumatoid arthritis because of its efficacy, long track record, and relatively favorable safety profile. Folic acid supplementation (typically 1 mg daily or an equivalent weekly dose) is given concurrently to reduce methotrexate-related adverse effects, including stomatitis, gastrointestinal upset, and cytopenias, by replenishing folate depleted through dihydrofolate reductase inhibition. Methotrexate is given once weekly, not daily, to minimize toxicity. Patients require baseline and periodic monitoring of liver enzymes and blood counts.

• B. Leflunomide is an alternative DMARD but does not require folic acid co-administration; it requires monitoring for hepatotoxicity.
• C. Minocycline is not a standard first-line DMARD for rheumatoid arthritis.
• D. Hydroxychloroquine requires baseline and annual ophthalmologic monitoring for retinopathy, not folic acid supplementation.
• E. Sulfasalazine is used for mild RA, especially in pregnancy, and does not require folic acid to prevent its specific toxicities.

Before starting a TNF-alpha inhibitor, patients must be screened for latent tuberculosis (tuberculin skin test or interferon-gamma release assay) and hepatitis B infection, because TNF-alpha inhibition can lead to reactivation of latent TB or hepatitis B, sometimes with severe or fulminant disease. If latent TB is found, treatment should be completed or substantially underway before starting the biologic. Hepatitis B carriers require antiviral prophylaxis or close monitoring. This screening is a required standard of care, not an optional step, prior to initiating any TNF-alpha inhibitor.

• A. Starting the medication without screening risks reactivation of latent tuberculosis or hepatitis B, which can be severe.
• B. Empiric isoniazid without first confirming latent TB infection is not appropriate and exposes the patient to unnecessary drug toxicity.
• D. A baseline chest CT is not routinely required; a chest radiograph may be used if the TB screening test is positive.
• E. Anti-CCP titer is useful for diagnosis but does not affect the decision to screen for infection before starting a TNF inhibitor.

Methotrexate is associated with hepatotoxicity, including transaminase elevation and, with prolonged use, hepatic fibrosis, as well as bone marrow suppression causing cytopenias. Periodic monitoring of liver function tests and complete blood count (typically every 4-12 weeks depending on duration of therapy) is recommended to detect these toxicities early. Methotrexate can also cause pulmonary toxicity, including pneumonitis and fibrosis, which is monitored clinically with attention to new respiratory symptoms rather than routine imaging in asymptomatic patients. Persistent transaminase elevation may prompt dose reduction or liver biopsy in select cases.

• A. Uric acid and urine protein are relevant to gout and lupus nephritis monitoring, not methotrexate toxicity.
• B. Glucose monitoring is relevant to corticosteroid use, not methotrexate.
• D. Renal monitoring is more relevant to drugs like NSAIDs or cyclosporine; methotrexate's major toxicities are hepatic and hematologic.
• E. Thyroid and lipid monitoring are not specific to methotrexate toxicity surveillance.

Chronic rheumatoid arthritis can cause erosive synovitis of the atlantoaxial joint and transverse ligament laxity, leading to atlantoaxial subluxation, which risks spinal cord compression during neck manipulation such as intubation. Flexion-extension lateral cervical spine radiographs assess the atlanto-dens interval and are the standard preoperative screening test in long-standing RA patients with neck symptoms before procedures requiring neck extension. If significant instability is found, the airway should be secured using techniques that avoid neck extension, such as fiberoptic intubation with the neck in a neutral position.

• B. Nerve conduction studies assess peripheral neuropathy, not cervical spine instability.
• C. Lumbar spine imaging is not relevant to the risk of cervical cord injury during intubation.
• D. Standard neck extension in the presence of atlantoaxial instability can cause spinal cord compression or injury.
• E. Epidural steroid injection does not address the structural risk of atlantoaxial instability during airway manipulation.

Felty syndrome is defined by the triad of chronic rheumatoid arthritis, splenomegaly, and neutropenia, and typically occurs in patients with long-standing, seropositive, erosive RA. The neutropenia predisposes patients to recurrent bacterial infections, and the spleen is often palpably enlarged due to sequestration. Management includes optimizing RA disease control with DMARDs such as methotrexate, and in refractory or severe cases, splenectomy or granulocyte colony-stimulating factor may be considered. The diagnosis is clinical, supported by the classic triad in the context of established RA.

• A. Lupus can cause cytopenias and splenomegaly but would not occur in the setting of 20 years of established seropositive RA with hand deformities.
• C. CLL typically presents with lymphocytosis rather than neutropenia, and is not linked to long-standing RA.
• D. Hairy cell leukemia causes pancytopenia with characteristic cells on blood smear, not specifically associated with RA.
• E. Sjögren syndrome causes dry eyes and dry mouth, not splenomegaly with neutropenia, as the defining feature.

Arthrocentesis with synovial fluid analysis under polarized light microscopy is the gold standard test for diagnosing acute gout. It reveals needle-shaped, negatively birefringent monosodium urate crystals and also allows exclusion of septic arthritis through cell count, Gram stain, and culture. Serum uric acid can be normal or even low during an acute flare and is therefore unreliable for diagnosis at that time. Synovial fluid analysis remains essential even when the clinical picture strongly suggests gout, because septic arthritis can mimic or coexist with a gout flare.

• A. Serum uric acid can be normal or low during an acute attack and does not confirm the diagnosis.
• C. Plain radiographs are usually normal early in gout and show changes like erosions only with chronic, recurrent disease.
• D. Dual-energy CT can detect urate deposits but is not the first-line or most practical confirmatory test in the acute setting.
• E. ESR and CRP are nonspecific markers of inflammation and cannot distinguish gout from other causes of acute monoarthritis.

Current guidelines support initiating urate-lowering therapy during an acute gout flare, provided effective anti-inflammatory treatment has been started, rather than waiting for the flare to resolve. Earlier initiation does not worsen flare duration or severity and improves long-term adherence. Starting allopurinol at a low dose and titrating slowly while continuing anti-inflammatory prophylaxis minimizes the risk of flare exacerbation. This patient, with recurrent flares, has a clear indication for urate-lowering therapy regardless of exact uric acid level.

• B. Waiting until the flare resolves is no longer considered necessary and may delay effective long-term management.
• C. A 24-hour urine uric acid is used to classify overproducers versus underexcretors but is not required before starting allopurinol and should not delay therapy.
• D. Febuxostat is an alternative urate-lowering agent, but delaying its start until after spontaneous resolution is unnecessary and uric acid does not normalize spontaneously without treatment.
• E. Permanently avoiding urate-lowering therapy is incorrect given recurrent flares, which is an indication for treatment.

HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), particularly in individuals of Han Chinese, Thai, and Korean descent. Guidelines recommend HLA-B*58:01 screening before starting allopurinol in high-risk populations, and a positive result is a contraindication to its use. The mechanism involves T-cell-mediated hypersensitivity triggered by the drug-HLA complex. Febuxostat is an alternative in patients who carry this allele.

• A. HLA-B*27 is associated with spondyloarthropathies, not allopurinol hypersensitivity.
• B. HLA-DR4 is associated with rheumatoid arthritis susceptibility, not allopurinol reactions.
• D. CYP2C9*3 affects metabolism of drugs like warfarin and phenytoin, not allopurinol hypersensitivity.
• E. TPMT deficiency predicts toxicity from thiopurine drugs such as azathioprine, not allopurinol.

Calcium pyrophosphate deposition disease (pseudogout) is characterized by rhomboid-shaped crystals that show weak positive birefringence under polarized light, in contrast to the needle-shaped, negatively birefringent crystals of gout. Chondrocalcinosis, seen as linear radiodensities within the hyaline or fibrocartilage on x-ray, supports the diagnosis. The knee is the most commonly affected joint. Synovial fluid is inflammatory, and the clinical presentation can closely mimic both gout and septic arthritis, making crystal analysis essential for diagnosis.

• B. Osteoarthritis does not typically present with this degree of acute inflammation or crystal findings.
• C. Gout crystals are needle-shaped and negatively birefringent, not rhomboid and positively birefringent.
• D. Septic arthritis would not show crystals on polarized microscopy, and chondrocalcinosis is not a feature.
• E. Rheumatoid arthritis synovial fluid does not contain crystals and has a different radiographic pattern.

In any patient with acute monoarticular arthritis and fever, septic arthritis must be excluded urgently, and arthrocentesis with synovial fluid cell count, Gram stain, and culture should be performed before starting antibiotics whenever possible. This allows identification of the causative organism and avoids compromising culture yield. Empiric antibiotics should be started promptly after fluid is obtained if septic arthritis is strongly suspected clinically, but obtaining the sample first is the priority next step. Imaging and empiric colchicine would delay diagnosis of a potentially joint-destroying infection.

• B. Starting antibiotics before obtaining synovial fluid can reduce culture sensitivity and delay identification of the organism.
• C. MRI is not the first step and would delay diagnostic arthrocentesis in a patient with suspected septic arthritis.
• D. Plain radiographs are often normal early in septic arthritis and do not provide the diagnostic fluid analysis needed.
• E. Empiric colchicine assumes a crystal arthropathy without first excluding septic arthritis, which can be rapidly destructive if missed.

A synovial fluid leukocyte count greater than 50,000/mm³, especially with more than 90% neutrophils, is highly suggestive of septic arthritis, although no single cutoff is both perfectly sensitive and specific. Inflammatory arthropathies such as gout or rheumatoid arthritis typically produce counts in the 2,000-50,000/mm³ range, while noninflammatory conditions like osteoarthritis produce counts under 2,000/mm³ with clear, viscous fluid. Gram stain and culture remain necessary for definitive diagnosis, but the markedly elevated neutrophil-predominant leukocyte count in this patient strongly raises concern for bacterial infection and warrants empiric antibiotic coverage pending culture results.

• A. A count of 15,000/mm³ with mononuclear cells is more consistent with an inflammatory but noninfectious arthropathy, such as early rheumatoid arthritis.
• C. Eosinophil predominance is unusual in septic arthritis and raises suspicion for other causes, such as parasitic infection or drug reaction.
• D. A count of 5,000/mm³ with lymphocyte predominance is more typical of a noninflammatory or chronic inflammatory process, not acute bacterial infection.
• E. A count under 2,000/mm³ with clear fluid is characteristic of a noninflammatory effusion, such as osteoarthritis.

Disseminated gonococcal infection classically presents with the triad of migratory polyarthralgia or tenosynovitis, dermatitis with pustular or vesiculopustular lesions on an erythematous base, and fever in a sexually active young adult. Tenosynovitis, particularly of the wrists, fingers, and ankles, is a hallmark feature that helps distinguish this from other causes of acute polyarthritis. Blood and synovial fluid cultures are often negative, so cultures of mucosal sites such as the cervix, urethra, pharynx, and rectum using nucleic acid amplification testing improve diagnostic yield. Treatment is with ceftriaxone.

• A. Secondary syphilis can cause a rash and systemic symptoms but does not typically cause tenosynovitis or necrotic pustules in this pattern.
• C. Reactive arthritis typically follows gastrointestinal or genitourinary infection by 1-4 weeks and is associated with conjunctivitis and urethritis rather than pustular skin lesions and tenosynovitis.
• D. Acute rheumatic fever follows streptococcal pharyngitis and presents with migratory large-joint arthritis but not tenosynovitis or pustular skin lesions.
• E. Systemic lupus erythematosus can cause polyarthritis but does not typically present with pustular skin lesions or tenosynovitis in this acute pattern.

In a sexually active young adult with gram-negative diplococci on synovial fluid Gram stain, disseminated gonococcal infection is the most likely cause of septic arthritis, and ceftriaxone is the empiric treatment of choice given rising fluoroquinolone resistance in Neisseria gonorrhoeae. Ceftriaxone also provides reasonable empiric coverage while culture and susceptibility results are pending. Vancomycin targets gram-positive organisms including MRSA and would not adequately treat a gonococcal infection. Fluoroquinolones and tetracyclines are not recommended as first-line therapy for gonococcal infection due to resistance concerns.

• A. Fluoroquinolone resistance in N. gonorrhoeae makes this inappropriate empiric therapy.
• B. Covers gram-positive organisms such as MRSA but not Neisseria gonorrhoeae.
• C. Covers gram-positive cocci but not gram-negative diplococci.
• D. Not recommended as monotherapy for gonococcal infection due to resistance.

The two-tiered serologic testing approach, an enzyme immunoassay (EIA) screen followed by a confirmatory Western blot if the EIA is positive or equivocal, is the recommended and most accurate test for diagnosing Lyme disease, including Lyme arthritis, in a patient with a compatible exposure history and prior erythema migrans. Synovial fluid PCR can support the diagnosis in equivocal cases but is not first-line. Borrelia burgdorferi is very difficult to culture from synovial fluid or blood, making culture and blood smear impractical and low-yield. Gram stain and culture are appropriate for bacterial septic arthritis, not Lyme arthritis.

• B. Appropriate for bacterial septic arthritis, not for Lyme arthritis, which has a sterile inflammatory synovial fluid.
• C. Borrelia burgdorferi is not reliably seen on peripheral blood smear.
• D. Used as an adjunct in select cases, not the standard initial diagnostic test.
• E. Borrelia is difficult to culture; this is not a practical diagnostic method.

This patient has classic features of inflammatory back pain: onset before age 40, insidious onset, improvement with exercise, worsening with rest, and morning stiffness lasting more than 30 minutes, plus enthesitis (heel pain), reduced chest expansion, and elevated inflammatory markers, all consistent with ankylosing spondylitis. This condition is strongly associated with HLA-B27 and primarily affects the sacroiliac joints and axial skeleton in young men. Mechanical back pain and disc herniation typically worsen with activity and improve with rest, the opposite pattern seen here. Fibromyalgia presents with diffuse chronic pain and normal inflammatory markers, and diffuse idiopathic skeletal hyperostosis occurs in older patients with spinal ligament calcification rather than active inflammation.

• A. Presents with diffuse widespread pain and tender points, with normal inflammatory markers.
• B. Pain pattern typically worsens with activity rather than improving with exercise.
• D. Pain typically worsens with activity and improves with rest, the opposite of this patient's pattern.
• E. Occurs in older adults and reflects ligamentous calcification rather than an inflammatory process.

In suspected axial spondyloarthritis with a normal plain radiograph, MRI of the sacroiliac joints is the best initial imaging modality because it can detect active inflammation, such as bone marrow edema, before structural damage becomes visible on x-ray. This allows earlier diagnosis of nonradiographic axial spondyloarthritis, which can later progress to radiographic ankylosing spondylitis. CT can show structural changes but involves radiation and does not reliably detect early inflammatory changes compared to MRI. Bone scan lacks specificity, and DXA assesses bone mineral density rather than inflammation.

• A. Delays diagnosis and treatment; MRI can detect inflammation earlier without waiting for structural changes.
• B. Nonspecific and not used as a standard tool for diagnosing sacroiliitis.
• C. Can show late structural damage but is less sensitive than MRI for early inflammatory changes and involves radiation.
• E. Assesses bone density, not inflammatory sacroiliitis.

This patient's combination of psoriasis, dactylitis (sausage digit), nail pitting with onycholysis, and distal interphalangeal joint involvement with negative rheumatoid factor and anti-CCP is characteristic of psoriatic arthritis. Dactylitis results from inflammation of the entire digit including tendons and joints and is a hallmark feature distinguishing psoriatic arthritis from other inflammatory arthropathies. Rheumatoid arthritis typically spares the DIP joints and is associated with symmetric small joint polyarthritis with positive rheumatoid factor or anti-CCP in most cases. Osteoarthritis can affect DIP joints but does not cause dactylitis or nail changes, and gout classically presents with episodic monoarticular attacks, often at the first metatarsophalangeal joint.

• A. Presents with acute monoarticular attacks, classically at the first MTP joint, not chronic dactylitis.
• B. Can involve DIP joints but does not cause dactylitis, nail pitting, or onycholysis.
• D. Presents with skin thickening and Raynaud phenomenon, not dactylitis or psoriatic nail changes.
• E. Typically spares the DIP joints and is usually seropositive for RF or anti-CCP.

NSAIDs, such as naproxen, are first-line pharmacologic therapy for axial spondyloarthritis, used at the maximum tolerated dose for at least 2 to 4 weeks to assess response, alongside physical therapy and exercise. Biologic agents such as TNF inhibitors (adalimumab) or IL-17 inhibitors (secukinumab) are reserved for patients who fail an adequate trial of at least two different NSAIDs. Methotrexate has not shown efficacy for axial disease, and systemic glucocorticoids are not recommended for long-term management of axial spondyloarthritis due to limited efficacy and significant side effects.

• A. A biologic reserved for NSAID-refractory disease, not first-line therapy.
• B. Reserved for patients with inadequate response to NSAID trials, not first-line therapy.
• D. Not effective for axial spondyloarthritis, though it may be used for peripheral joint involvement in some spondyloarthropathies.
• E. Not recommended for long-term management of axial disease due to lack of sustained efficacy and side effects.

This patient meets multiple domains of the SLICC/ACR classification criteria for systemic lupus erythematosus, including malar rash with photosensitivity, nonerosive polyarthritis, hematologic abnormalities (leukopenia, thrombocytopenia, and likely hemolytic anemia), renal involvement (proteinuria with red cell casts suggesting lupus nephritis), and strongly positive ANA with anti-dsDNA, which is highly specific for SLE. Rheumatoid arthritis causes a symmetric erosive polyarthritis but not malar rash, renal casts, or anti-dsDNA positivity. Dermatomyositis presents with proximal muscle weakness and characteristic skin findings such as heliotrope rash, not malar rash sparing the nasolabial folds. Mixed connective tissue disease and drug-induced lupus do not typically present with anti-dsDNA positivity and significant renal involvement as seen here.

• A. Causes a symmetric erosive polyarthritis but does not explain the malar rash, renal casts, or anti-dsDNA positivity.
• B. Associated with anti-histone antibodies rather than anti-dsDNA, and typically lacks renal involvement.
• C. Features overlapping connective tissue disease findings but typically lacks high-titer anti-dsDNA and nephritis of this severity.
• E. Presents with proximal muscle weakness and characteristic skin findings, not malar rash and nephritis.

Minor salivary gland biopsy showing focal lymphocytic sialadenitis with a focus score of 1 or more foci per 4 mm² is a required objective criterion in the ACR-EULAR classification of Sjogren syndrome and provides histologic confirmation when serology and sicca symptoms are present. It also helps exclude other causes of gland infiltration such as IgG4-related disease or lymphoma. Schirmer testing and serology support the diagnosis but are not confirmatory on their own. Biopsy is the most specific and guideline-endorsed confirmatory test.

• B. ANA is a nonspecific screening test, not confirmatory for Sjogren syndrome.
• C. Rheumatoid factor is nonspecific and can be positive in many autoimmune conditions.
• D. Sialography shows ductal changes but is not part of standard classification criteria and is less specific.
• E. Scintigraphy assesses salivary gland function but lacks the specificity of histologic confirmation.

Mixed connective tissue disease is an overlap syndrome combining features of systemic sclerosis (Raynaud phenomenon, puffy fingers, dysmotility), SLE (arthritis), and myositis, defined serologically by a high titer of anti-U1-RNP antibody in the absence of antibodies specific for the other individual connective tissue diseases. The combination of Raynaud phenomenon, synovitis, and esophageal dysmotility with isolated high-titer anti-U1-RNP is the classic presentation. Anti-Scl-70 and anti-centromere point to systemic sclerosis, while anti-Smith and anti-dsDNA point to SLE, and both are negative here. This serologic pattern with overlapping clinical features is diagnostic of MCTD.

• B. Limited systemic sclerosis would show sclerodactyly and is usually anti-centromere positive.
• C. SLE would typically show anti-dsDNA or anti-Smith antibodies, which are negative here.
• D. Rheumatoid arthritis does not explain Raynaud phenomenon or esophageal dysmotility and lacks anti-U1-RNP specificity.
• E. Undifferentiated connective tissue disease is used when no specific overlap antibody pattern is identified, which does not fit this case.

Dermatomyositis has a well-established association with occult malignancy, particularly ovarian, lung, pancreatic, gastric, and colorectal cancers and lymphoma, with the risk being highest in the first year after diagnosis. Guidelines recommend age- and sex-appropriate cancer screening (mammography, Pap smear, colonoscopy, PSA as appropriate) supplemented by CT of the chest, abdomen, and pelvis, especially in older patients or those with constitutional symptoms like unintentional weight loss. Whole-body PET is not recommended as a routine first-line screening tool due to cost and lack of proven superiority over directed screening. Tumor markers alone and colonoscopy alone are insufficiently comprehensive given the broad range of associated malignancies.

• A. Tumor markers alone are not sufficiently sensitive or comprehensive for malignancy screening in dermatomyositis.
• B. PET scan is not recommended as first-line screening due to cost, lower specificity, and lack of proven mortality benefit over standard screening.
• C. Colonoscopy alone misses other malignancies strongly associated with dermatomyositis such as ovarian and lung cancer.
• E. Malignancy risk is significantly increased in dermatomyositis, especially within the first year of diagnosis.

Giant cell arteritis typically presents in patients older than 50 years with new-onset headache, jaw claudication (pain with chewing due to ischemia of the masseter muscles), temporal artery tenderness or diminished pulse, and markedly elevated inflammatory markers, often with concurrent polymyalgia rheumatica symptoms like shoulder and hip girdle stiffness. Jaw claudication is highly specific for GCA and reflects vasculitic narrowing of the external carotid artery branches. Prompt recognition is critical because untreated GCA can cause irreversible vision loss from anterior ischemic optic neuropathy. The combination of age, new headache, jaw claudication, and markedly elevated ESR/CRP in this patient is classic for GCA.

• A. Trigeminal neuralgia causes brief, electric shock-like facial pain, not jaw claudication with systemic inflammation.
• B. Polyarteritis nodosa typically involves medium-sized vessels in the kidneys, gut, and peripheral nerves, not the temporal artery, and does not classically cause jaw claudication.
• C. Migraine does not explain jaw claudication, temporal artery findings, or elevated inflammatory markers.
• E. TMJ dysfunction does not cause markedly elevated ESR/CRP or temporal artery tenderness.

When giant cell arteritis is strongly suspected, especially with warning signs like amaurosis fugax, high-dose glucocorticoids (typically prednisone 60 mg/day) should be started immediately without waiting for biopsy, because the primary goal is to prevent irreversible vision loss. Temporal artery biopsy remains the diagnostic gold standard, but glucocorticoid-induced histologic changes take several weeks to appear, so starting steroids promptly does not significantly reduce biopsy sensitivity if performed within 2 weeks. Delaying treatment risks permanent blindness from anterior ischemic optic neuropathy or central retinal artery occlusion. Aspirin may be added as adjunctive therapy but does not substitute for glucocorticoids in preventing vision loss.

• A. Imaging is not required before starting glucocorticoids when clinical suspicion for GCA with visual symptoms is high.
• B. Delaying treatment until biopsy confirmation risks permanent vision loss.
• C. Aspirin alone does not adequately treat the underlying vasculitic inflammation or prevent vision loss.
• D. Methotrexate is used as a steroid-sparing agent in relapsing disease, not as initial emergency therapy.

Takayasu arteritis is a large-vessel vasculitis that predominantly affects women under 40 years old, causing inflammation and stenosis of the aorta and its major branches, classically presenting with limb claudication, asymmetric blood pressures and pulses, and bruits over affected vessels along with constitutional symptoms and elevated inflammatory markers. Imaging showing smooth, long-segment arterial narrowing with wall thickening in a young patient is characteristic and distinguishes it from atherosclerotic disease, which typically shows focal, irregular plaques in older patients with risk factors. Giant cell arteritis affects a similar vessel distribution but occurs in patients older than 50 years. Early recognition is important to guide glucocorticoid therapy and prevent vascular complications such as aneurysm or critical limb ischemia.

• A. Giant cell arteritis occurs in patients older than 50 and typically involves cranial branches of the carotid artery.
• B. Fibromuscular dysplasia classically causes a 'string of beads' appearance, usually in renal or carotid arteries, not smooth long-segment aortic arch narrowing with systemic inflammation.
• C. Thromboangiitis obliterans affects small and medium distal vessels in smokers, not the aortic arch.
• E. Atherosclerotic stenosis is unlikely at this age and typically shows focal, irregular lesions rather than smooth long-segment inflammatory narrowing.

The triad of upper respiratory tract disease (chronic sinusitis, saddle-nose deformity from cartilage destruction), lower respiratory tract disease (cavitary nodules, hemoptysis), and rapidly progressive glomerulonephritis strongly suggests granulomatosis with polyangiitis (GPA). c-ANCA with anti-PR3 specificity is found in over 90% of patients with active, generalized GPA and is highly specific when combined with this clinical picture. GPA is a necrotizing granulomatous vasculitis of small and medium vessels. Diagnosis is confirmed by biopsy showing necrotizing granulomatous inflammation, but the clinical-serologic correlation here is diagnostic.

• B. Eosinophilic granulomatosis with polyangiitis requires a history of asthma and marked peripheral eosinophilia, which are absent here.
• C. Goodpasture syndrome causes pulmonary-renal syndrome via anti-glomerular basement membrane antibodies, not ANCA, and does not cause sinusitis or saddle-nose deformity.
• D. Polyarteritis nodosa is ANCA-negative, spares the lungs, and classically causes mononeuritis multiplex and renal infarction rather than glomerulonephritis.
• E. Microscopic polyangiitis causes glomerulonephritis and pulmonary hemorrhage but lacks granulomatous upper airway destruction like saddle-nose deformity, and is associated with p-ANCA/MPO rather than c-ANCA/PR3.

This patient has pulmonary-renal vasculitis without upper airway granulomatous disease, cavitary lung lesions, or asthma/eosinophilia, pointing away from granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Microscopic polyangiitis (MPA) is a necrotizing small-vessel vasculitis that typically presents with rapidly progressive glomerulonephritis and pulmonary capillaritis (causing diffuse ground-glass opacities or alveolar hemorrhage) without granuloma formation. MPA is strongly associated with p-ANCA/anti-myeloperoxidase antibodies, distinguishing it serologically from GPA, which is associated with c-ANCA/PR3. The absence of nasal/sinus disease and cavitary nodules further argues against GPA.

• A. GPA typically involves destructive upper airway disease and cavitary pulmonary nodules and is associated with c-ANCA/PR3, not p-ANCA/MPO.
• B. Cryoglobulinemic vasculitis is typically associated with hepatitis C infection and positive cryoglobulins, not ANCA positivity.
• C. Polyarteritis nodosa is ANCA-negative and does not cause glomerulonephritis or pulmonary involvement; it causes renal artery microaneurysms and infarcts.
• E. EGPA requires a history of asthma and eosinophilia, both absent in this patient.

This patient has classic polyarteritis nodosa (PAN): mononeuritis multiplex (asymmetric sensorimotor deficits from vasa nervorum ischemia), renal artery involvement with hypertension, livedo reticularis, and subcutaneous nodules, with angiographic microaneurysms of medium-sized vessels. PAN is ANCA-negative, and roughly a third of cases are associated with chronic hepatitis B infection, in which circulating hepatitis B surface antigen-antibody immune complexes deposit in medium-sized muscular artery walls, triggering complement activation and necrotizing transmural inflammation. This immune complex-mediated injury leads to fibrinoid necrosis, aneurysm formation, and downstream tissue ischemia, distinct from the ANCA-mediated pauci-immune vasculitis mechanism.

• B. This describes the mechanism of ANCA-associated vasculitides such as GPA, which are ANCA-positive and typically granulomatous, unlike this patient's ANCA-negative PAN.
• C. IgA-mediated small-vessel deposition describes IgA vasculitis, which affects small vessels and classically occurs in children with purpura and GI symptoms.
• D. Cryoglobulinemic vasculitis is typically associated with hepatitis C, not hepatitis B, and affects small vessels rather than medium-sized muscular arteries.
• E. Anti-GBM antibody disease causes isolated pulmonary-renal capillaritis, not medium-vessel disease with microaneurysms or mononeuritis multiplex.

This child has the classic tetrad of IgA vasculitis (formerly Henoch-Schönlein purpura): palpable purpura in a dependent distribution (legs and buttocks), arthralgia/arthritis, abdominal pain (from bowel wall vasculitis, sometimes with GI bleeding or intussusception), and renal involvement (hematuria and proteinuria from IgA-mediated glomerulonephritis). It frequently follows an upper respiratory infection and typically occurs in children aged 3 to 10 years. The normal platelet count distinguishes this palpable purpura from thrombocytopenic causes of purpura, confirming that the lesions result from vasculitis rather than a bleeding disorder.

• A. Hemolytic uremic syndrome presents with thrombocytopenia, hemolytic anemia, and acute kidney injury after diarrheal illness, not palpable purpura with normal platelets.
• B. Systemic lupus erythematosus is uncommon in this age group and would not typically present with this classic purpura-arthritis-abdominal pain triad following a respiratory infection.
• C. Meningococcemia causes a rapidly progressive petechial/purpuric rash with fever and hemodynamic instability, not a subacute presentation with normal vital signs.
• E. Immune thrombocytopenic purpura causes petechiae/ecchymoses with thrombocytopenia, not palpable purpura, arthralgia, or renal involvement, and platelets are normal here.

This child meets diagnostic criteria for classic Kawasaki disease: fever for at least 5 days plus at least four of five principal features (bilateral conjunctival injection, oral mucosal changes, polymorphous rash, extremity changes, cervical lymphadenopathy). The most appropriate next step is to obtain a baseline echocardiogram to assess for coronary artery abnormalities and to begin treatment with intravenous immunoglobulin (IVIG) plus high-dose aspirin, ideally within the first 10 days of illness, to reduce the risk of coronary artery aneurysm formation, which occurs in up to 25% of untreated children. Thrombocytosis and markedly elevated CRP are supportive laboratory findings. Early treatment significantly reduces cardiac complications.

• B. Juvenile idiopathic arthritis does not explain the mucocutaneous findings, conjunctivitis, or lymphadenopathy, and steroids alone are not first-line therapy for Kawasaki disease.
• C. This presentation is not consistent with SLE, which is rare in this age group and would not produce this specific symptom complex.
• D. Negative cultures and the classic constellation of findings make bacterial sepsis unlikely; empiric antibiotics do not address the underlying vasculitis or prevent coronary aneurysms.
• E. This presentation does not suggest streptococcal infection such as rheumatic fever, and it lacks major Jones criteria findings like carditis or chorea.

This young girl has oligoarticular juvenile idiopathic arthritis (JIA), the most common JIA subtype, which carries the highest risk of chronic anterior uveitis, especially in young girls with a positive ANA. This uveitis is typically asymptomatic until it causes vision-threatening complications, so routine slit-lamp examination by an ophthalmologist is required even in the absence of eye symptoms. Screening frequency is guided by age at onset, ANA status, and disease duration, with ANA-positive young children needing examinations as often as every 3 months for the first several years. Fundoscopy alone is inadequate because anterior uveitis (iridocyclitis) is best detected by slit-lamp examination, not by funduscopy, which examines the posterior segment.

• A. Complement levels are relevant to monitoring lupus activity, not JIA-associated uveitis.
• B. Renal involvement is not a feature of oligoarticular JIA; this is more relevant to IgA vasculitis or lupus nephritis.
• C. Dilated fundoscopy by a primary care physician examines the posterior segment and will miss anterior uveitis, which requires slit-lamp examination by an ophthalmologist.
• D. Cardiac involvement is not a recognized complication of oligoarticular JIA, unlike systemic JIA which can cause pericarditis.

The combination of quotidian (daily spiking, once- or twice-daily) fever with an evanescent salmon-colored rash that appears during febrile spikes, arthritis, hepatosplenomegaly, lymphadenopathy, and markedly elevated ferritin is characteristic of systemic juvenile idiopathic arthritis (systemic JIA, formerly Still disease). The dramatically elevated ferritin reflects the macrophage activation and systemic inflammation that drive this disease and helps distinguish it from infectious or malignant causes, although extremely high ferritin should also prompt evaluation for macrophage activation syndrome, a known complication. ANA and rheumatoid factor are typically negative in systemic JIA, unlike other JIA subtypes.

• A. Acute rheumatic fever presents with migratory polyarthritis following streptococcal pharyngitis and would show evidence of antecedent strep infection, not a quotidian fever pattern with salmon rash.
• B. Kawasaki disease causes a persistent rash and conjunctivitis, not a fever-associated evanescent salmon rash, and typically resolves within 2 weeks rather than persisting for 3 weeks.
• C. While leukemia can cause fever, arthralgia, and hepatosplenomegaly, the markedly elevated ferritin and classic evanescent salmon rash with quotidian fever favor systemic JIA, and peripheral smear/marrow would show blasts in leukemia.
• D. Infective endocarditis would show a positive blood culture or vegetation on echocardiogram in most cases, not this fever and rash pattern with negative cultures.

The World Health Organization classifies bone density by DXA T-score: normal is -1.0 or higher, low bone mass (osteopenia) is between -1.0 and -2.5, and osteoporosis is -2.5 or lower. This patient's lowest T-score is -1.8, which falls in the osteopenic range. Severe osteoporosis requires a T-score of -2.5 or lower plus a fragility fracture. The diagnosis is based on the lowest T-score among the sites measured (spine, femoral neck, or total hip).

• A. Severe osteoporosis requires a T-score of -2.5 or lower plus a fragility fracture, neither of which is present.
• B. Osteoporosis requires a T-score of -2.5 or lower; -1.8 does not meet this threshold.
• C. Osteomalacia is a defect in bone mineralization diagnosed by biochemical abnormalities (low calcium/phosphate, high PTH), not by DXA T-score.
• D. A T-score of -1.8 is below the normal cutoff of -1.0, so bone density is not normal.

Bisphosphonates are associated with rare but serious atypical subtrochanteric or femoral shaft fractures, which often present with prodromal dull, aching thigh or groin pain weeks to months before complete fracture. Patients should be counseled to report such pain promptly so imaging can be obtained. Oral bisphosphonates must be taken on an empty stomach with a full glass of water, and the patient should remain upright for at least 30-60 minutes to reduce esophageal irritation, not lying down. Osteonecrosis of the jaw is more strongly associated with invasive dental procedures (extractions, implants) and high-dose IV bisphosphonates used in cancer, not with routine dental cleanings.

• B. Mild heartburn is a common esophageal side effect, not a sign of osteonecrosis of the jaw, and does not require immediate discontinuation.
• C. Patients should remain upright, not lying down, after taking oral bisphosphonates to minimize esophageal irritation.
• D. Oral bisphosphonates should be taken on an empty stomach, not with food, for adequate absorption; this does not reduce atypical fracture risk.
• E. Routine dental cleanings are safe; the osteonecrosis risk is mainly with invasive procedures like extractions, especially with high-dose IV therapy.

This patient has the classic biochemical pattern of vitamin D deficiency osteomalacia: low serum calcium and phosphate, secondary hyperparathyroidism (elevated PTH as the parathyroid gland compensates for hypocalcemia), and elevated alkaline phosphatase reflecting increased osteoblastic activity from impaired bone mineralization. Risk factors include limited sun exposure and poor dietary intake, common in homebound elderly patients. Diffuse bone pain and proximal myopathy with a waddling gait are classic clinical features. The diagnosis is confirmed by a low serum 25-hydroxyvitamin D level, and treatment is vitamin D and calcium repletion.

• A. Primary hyperparathyroidism typically causes elevated, not low, serum calcium.
• C. Osteoporosis is a disorder of bone density with normal calcium, phosphate, PTH, and alkaline phosphatase.
• D. Paget disease causes an isolated elevated alkaline phosphatase with normal calcium, phosphate, and PTH.
• E. Multiple myeloma typically causes hypercalcemia, renal insufficiency, and anemia, not this biochemical pattern.

This patient's isolated marked elevation of alkaline phosphatase with normal calcium, phosphate, and PTH, along with bone pain, deformity, and warmth over the affected bone, is classic for Paget disease of bone, caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Intravenous bisphosphonates such as zoledronic acid are first-line therapy for symptomatic Paget disease, as they suppress osteoclast activity and normalize alkaline phosphatase. Treatment is indicated for symptomatic disease, involvement of weight-bearing bones, or risk of complications like deformity or fracture.

• A. Cinacalcet is a calcimimetic used for hyperparathyroidism, not Paget disease.
• B. Denosumab is used mainly for osteoporosis and bone metastases; bisphosphonates remain first-line for Paget disease.
• C. Calcitriol treats vitamin D deficiency or hypoparathyroidism, not Paget disease.
• E. Teriparatide, a PTH analog, stimulates bone formation and is used for severe osteoporosis, not Paget disease.

This patient's presentation is classic for osteoarthritis: pain that worsens with activity and improves with rest, brief morning stiffness lasting less than 30 minutes, and bony enlargement of the distal interphalangeal joints (Heberden nodes). Crepitus on range of motion reflects cartilage loss and irregular joint surfaces. Osteoarthritis is a clinical diagnosis in a patient with typical risk factors (age, joint distribution) and can be supported by radiographs showing joint space narrowing, osteophytes, and subchondral sclerosis. The absence of joint warmth, erythema, or prolonged stiffness argues against an inflammatory arthritis.

• A. Rheumatoid arthritis typically causes prolonged morning stiffness (over 30-60 minutes), symmetric MCP/PIP involvement, and systemic symptoms.
• C. Psoriatic arthritis is associated with psoriasis, dactylitis, and nail changes, not isolated DIP bony enlargement without inflammation.
• D. Septic arthritis presents acutely with a hot, swollen, severely painful joint and systemic signs of infection.
• E. Gout presents with acute, intensely painful, warm, erythematous monoarticular attacks, not chronic bilateral degenerative changes.

In patients with osteoarthritis who have contraindications to systemic NSAIDs, such as chronic kidney disease, peptic ulcer disease, or concurrent use of nephrotoxic medications, topical NSAIDs like diclofenac gel are preferred because they provide local analgesia with minimal systemic absorption and therefore substantially lower risk of gastrointestinal bleeding, nephrotoxicity, and cardiovascular events. Oral NSAIDs, whether non-selective or COX-2 selective, carry meaningful risk of worsening renal function and gastrointestinal bleeding in this patient with CKD and prior ulcer disease. Topical NSAIDs are recommended by guidelines as first-line therapy for knee osteoarthritis, especially in older adults with these comorbidities.

• A. Oral ketorolac is a potent NSAID with high GI and renal toxicity risk and is not appropriate for chronic OA management.
• C. Oral ibuprofen can worsen renal function and reactivate peptic ulcer disease in this patient.
• D. Oral naproxen carries the same systemic GI and renal risks as other oral NSAIDs.
• E. Celecoxib has lower GI risk than non-selective NSAIDs but still poses renal risk and is not preferred in CKD.

Fibromyalgia is characterized by chronic widespread musculoskeletal pain, fatigue, non-restorative sleep, and cognitive difficulties ('fibro fog'), with multiple tender points on examination and no evidence of synovitis or systemic inflammation. It is a diagnosis of exclusion, confirmed by normal inflammatory markers (ESR, CRP), normal thyroid function, and normal creatine kinase, which rule out inflammatory, endocrine, or muscle disease as the cause of the symptoms. Diagnosis is primarily clinical, based on widespread pain index and symptom severity criteria, rather than specific laboratory or imaging findings.

• A. Systemic lupus erythematosus causes multisystem involvement with abnormal serologies (ANA, anti-dsDNA) and often cytopenias or renal disease.
• B. Polymyositis causes proximal muscle weakness with markedly elevated creatine kinase, which is absent in this patient.
• C. Polymyalgia rheumatica causes proximal shoulder and hip girdle pain and stiffness with an elevated ESR, typically in patients over 50.
• D. Hypothyroid myopathy would show an elevated TSH and often elevated creatine kinase, both of which are normal here.

This patient has clinical features of carpal tunnel syndrome, including nocturnal paresthesias in a median nerve distribution and positive Tinel and Phalen signs. Nerve conduction studies are the most accurate test to confirm median nerve entrapment at the wrist, showing prolonged distal motor and sensory latencies across the carpal tunnel. Clinical diagnosis alone has only moderate accuracy, so electrodiagnostic testing is used to confirm the diagnosis, assess severity, and guide the decision between conservative and surgical management. Imaging and thyroid testing may be used to evaluate for underlying causes but are not the confirmatory test.

• A. Wrist radiographs do not show soft tissue or nerve compression and are not used to diagnose carpal tunnel syndrome.
• C. Thyroid testing can identify a contributing cause such as hypothyroidism but does not confirm median nerve entrapment.
• D. EMG of the deltoid evaluates for proximal or axillary nerve pathology, not median nerve entrapment at the wrist.
• E. Cervical spine MRI evaluates for radiculopathy, which is less likely given the isolated median nerve distribution and absence of neck pain.

This patient has preserved passive range of motion with markedly limited and weak active range of motion, a positive drop-arm test, and weakness on resisted abduction and external rotation, all of which point to a rotator cuff tear rather than a capsular process. In adhesive capsulitis, both active and passive range of motion are restricted because the joint capsule itself is contracted. The history of acute injury during lifting followed by persistent weakness also favors a structural tendon tear over an inflammatory capsular process. MRI or ultrasound can confirm the diagnosis if surgical repair is being considered.

• B. Adhesive capsulitis causes global restriction of both active and passive motion, which is not seen here since passive abduction is full.
• C. Osteoarthritis typically causes gradual onset of pain and stiffness with crepitus, not an acute weakness after lifting with a positive drop-arm test.
• D. Cervical radiculopathy would be expected to cause neck pain, dermatomal sensory changes, or reflex changes rather than isolated rotator cuff weakness.
• E. Biceps tendon rupture causes a visible deformity (Popeye sign) and weakness in forearm supination, not isolated abduction weakness.

This patient has pain over the radial styloid reproduced by ulnar deviation of the wrist with the thumb clasped in a fist, a positive Finkelstein test, which is characteristic of de Quervain tenosynovitis. This condition results from overuse of the abductor pollicis longus and extensor pollicis brevis tendons, commonly seen in new mothers from repetitive lifting of an infant with the thumbs extended. Treatment includes thumb spica splinting, NSAIDs, and activity modification, with corticosteroid injection for refractory cases. The absence of nocturnal paresthesias and normal grip strength argue against median nerve or joint pathology.

• A. A scaphoid fracture would typically follow a fall onto an outstretched hand and show tenderness in the anatomic snuffbox, not a positive Finkelstein test.
• C. First carpometacarpal osteoarthritis causes chronic grinding pain at the thumb base with a positive grind test, usually in older patients, not an acute postpartum presentation.
• D. Carpal tunnel syndrome presents with nocturnal paresthesias in a median nerve distribution and positive Tinel/Phalen signs, not isolated radial styloid tenderness.
• E. Intersection syndrome causes pain and crepitus more proximally where the first and second dorsal compartments cross, rather than at the radial styloid with a positive Finkelstein test.

This patient has saddle anesthesia and decreased anal sphincter tone with new urinary retention, findings concerning for cauda equina syndrome, a surgical emergency. His history of prostate cancer raises additional concern for vertebral metastasis causing cord or cauda equina compression. Emergent MRI of the lumbosacral spine is the most appropriate next step to confirm the diagnosis and localize the lesion so that urgent surgical decompression can be arranged, since delay increases the risk of permanent neurologic deficit. Plain radiographs lack the sensitivity to detect soft tissue or epidural compression.

• A. Waiting a week for imaging risks permanent neurologic damage; cauda equina syndrome requires emergent evaluation.
• C. Lumbar puncture is not indicated and could be hazardous if there is a mass lesion causing compression.
• D. Plain radiographs cannot adequately visualize the spinal canal or cauda equina compression and would delay definitive diagnosis.
• E. Conservative management with NSAIDs and physical therapy is inappropriate and dangerous when cauda equina syndrome is suspected.