IM7.1-22 | Rheumatologic Problems — Graded Quiz

Correct. Anti-CCP antibody (anti-citrullinated protein antibody) is not only highly specific for RA (>90%) but is also the strongest serological predictor of erosive, progressive joint damage. Strongly positive anti-CCP correlates with aggressive disease course requiring early combination DMARD therapy. RF has lower specificity (~80% for RA, may be positive in hepatitis C, Sjogren's, SBE) and is a weaker prognostic marker than anti-CCP. Elevated ESR reflects non-specific inflammation.

Anti-CCP antibody: specificity >90% for RA (versus RF ~80%). Anti-CCP strongly predicts erosive disease and poor structural outcome. Seropositive RA (RF+ and/or anti-CCP+) has a worse prognosis than seronegative RA and warrants early, aggressive treat-to-target DMARD therapy.

Anti-CCP antibody has the highest specificity for RA (>90%) AND is the strongest predictor of erosive disease. RF has lower specificity and is a weaker prognostic marker. Elevated ESR is non-specific. Anti-CCP positivity should prompt early aggressive DMARD therapy to prevent irreversible joint damage.

Correct. Rising proteinuria, haematuria, declining renal function, rising anti-dsDNA, and falling complement in a patient with SLE represent a lupus nephritis flare. Renal biopsy is mandatory to classify lupus nephritis (ISN/RPS Classes I-VI) because treatment is class-dependent: Class III/IV (proliferative) requires induction with pulse methylprednisolone plus mycophenolate mofetil (MMF) or cyclophosphamide. Class V (membranous) may be treated with MMF. Without renal biopsy, appropriate immunosuppression cannot be selected. Delaying treatment risks irreversible nephron loss.

Lupus nephritis flare markers: rising anti-dsDNA titres, falling complement (C3/C4), new/worsening proteinuria, haematuria, rising creatinine. Renal biopsy is mandatory to guide treatment selection. ISN/RPS Class III/IV (proliferative) = pulse steroids + MMF or cyclophosphamide induction. Anti-dsDNA titres correlate with lupus nephritis activity and can be used to monitor flares.

Lupus nephritis flare: rising proteinuria + haematuria + rising creatinine + rising anti-dsDNA + low complement in a known SLE patient requires URGENT renal biopsy to classify the nephritis (ISN/RPS I-VI). Treatment is class-dependent: proliferative classes (III/IV) need pulse steroids + MMF or cyclophosphamide. Do not delay with conservative measures — early biopsy and targeted treatment prevent permanent renal damage.

Correct. A synovial WBC of 68,000/mm3 (>50,000 is the threshold of concern) with 90% neutrophils and fever raises the critical differential of septic arthritis versus crystal arthropathy. Gout and CPPD can produce high neutrophil counts, but septic arthritis is a joint-threatening, potentially life-threatening emergency that must be excluded first. Synovial fluid Gram stain and culture plus blood cultures are mandatory. Importantly, a previous history of gout does NOT exclude concurrent septic arthritis — both can coexist. Serum uric acid is unreliable in the acute setting (can be normal during an acute gout attack due to inflammatory stress-induced renal urate excretion).

Septic arthritis rule: synovial WBC >50,000/mm3 (especially >100,000) with predominant neutrophils and fever = septic arthritis until proven otherwise. Order synovial fluid Gram stain + culture AND blood cultures. Do NOT withhold antibiotics pending culture if clinical suspicion is high. Gout and septic arthritis can coexist. Serum uric acid can be NORMAL during an acute gout attack — never use a normal value to exclude gout.

Key clinical rule: never assume crystal arthropathy when synovial WBC >50,000/mm3 with fever — septic arthritis must be excluded first. Synovial fluid culture and blood cultures are mandatory. Serum uric acid is unreliable in the acute setting (can be normal during a gout attack). A history of previous gout does NOT exclude concurrent septic arthritis.

Correct. Methotrexate pneumonitis is an idiosyncratic, potentially fatal drug reaction that presents with progressive dyspnoea, dry cough, and bilateral ground-glass opacities on HRCT. It can occur at any time during MTX therapy (not only at dose changes). The mandatory first step is to STOP methotrexate immediately. After excluding infection (BAL or sputum for bacterial, fungal, and TB), high-dose corticosteroids are given (prednisolone 1 mg/kg). MTX-related lung toxicity is one of the reasons a baseline chest X-ray and periodic monitoring are required. RA itself causes ILD (usually UIP or NSIP pattern), but ILD progression on MTX therapy should first raise drug toxicity before attributing to RA.

Methotrexate toxicities: (1) Hepatotoxicity — monitor LFT; (2) Myelosuppression — FBC every 3 months; (3) Pneumonitis — stop MTX immediately if progressive dyspnoea/dry cough/HRCT ground-glass changes, then exclude infection and give corticosteroids; (4) Mucositis — prevented by folic acid 5 mg weekly. MTX is teratogenic (Category X) — effective contraception mandatory for both sexes during therapy.

Methotrexate pneumonitis is an acute idiosyncratic toxicity — not dose-dependent — presenting as progressive dyspnoea, dry cough, and bilateral ground-glass opacities. Immediate action: stop methotrexate, exclude infection, and give high-dose corticosteroids. This is distinct from RA-ILD (which is a complication of the disease, not the drug). A baseline CXR and annual monitoring are part of MTX safety protocol.

Correct. Ankylosing spondylitis (AS) is the prototype spondyloarthropathy. NSAIDs are the recommended first-line pharmacological therapy for AS/axial spondyloarthritis — they provide both symptom relief and potentially retard radiographic progression. Conventional DMARDs (methotrexate, hydroxychloroquine) are NOT effective for the axial manifestations of AS (they may be used for peripheral arthritis). Systemic corticosteroids are also not effective for axial disease. If NSAIDs fail after 2-4 weeks at adequate doses, biologic therapy (TNF-alpha inhibitor or IL-17 inhibitor) is indicated.

AS treatment hierarchy: (1) NSAIDs first-line (full dose, 2-4 weeks); (2) Physiotherapy — mandatory alongside pharmacotherapy; (3) Biologic DMARD (TNF-alpha inhibitor or IL-17 inhibitor, e.g., secukinumab) if NSAID failure. Conventional DMARDs (MTX, HCQ, sulfasalazine) are NOT effective for axial AS. HLA-B27 is positive in ~90% of AS. Complications: uveitis (most common extra-articular), aortic regurgitation, ILD, amyloidosis.

Ankylosing spondylitis (axial spondyloarthropathy) first-line treatment: NSAIDs at full anti-inflammatory doses for 2-4 weeks. Conventional DMARDs (methotrexate, hydroxychloroquine) do NOT work for axial disease. Biologics (TNF inhibitors, IL-17 inhibitors) are second-line after NSAID failure. Physiotherapy (spinal extension exercises) is equally important as pharmacotherapy and must be prescribed concurrently.

Correct. The radiographic hallmarks of RA are: periarticular osteoporosis, marginal erosions (at joint margins, where pannus attacks), uniform joint space narrowing, and soft-tissue swelling — primarily affecting MCPs, PIPs, and wrists. In contrast, osteoarthritis shows: osteophytes (new bone formation), subchondral sclerosis, subchondral cysts, asymmetric joint space narrowing — predominantly at the DIP joints and first CMCJ in the hand. Heberden nodes (DIP osteophytes) are characteristic of osteoarthritis and are NOT a feature of RA. RA classically spares the DIP joints.

Radiographic differentiation: RA = periarticular osteoporosis + marginal erosions + symmetric JSN at MCPs/PIPs/wrists (DIP spared). OA = osteophytes + subchondral sclerosis/cysts + asymmetric JSN at DIP/first CMCJ (Heberden nodes at DIP, Bouchard at PIP). Psoriatic arthritis = erosions + new bone formation ('pencil-in-cup'), DIP involved, may show periostitis.

RA X-ray hallmarks: periarticular osteoporosis, marginal erosions, uniform JSN — at MCPs, PIPs, wrists. RA typically SPARES the DIP joints. OA X-ray hallmarks: osteophytes, subchondral sclerosis, asymmetric JSN — predominantly at DIP, first CMCJ. Heberden nodes (DIP osteophytes) are OA, not RA. Bouchard nodes are PIP osteophytes in OA.

Correct. Long-term corticosteroid use (any dose for >3 months) causes glucocorticoid-induced osteoporosis (GIOP) via suppression of osteoblast function and enhancement of osteoclast-mediated bone resorption. For patients on long-term corticosteroids, GIOP prevention requires: calcium (1000-1200 mg/day) + vitamin D (800-1000 IU/day) for all patients, PLUS an oral bisphosphonate (alendronate or risedronate) if FRAX score exceeds thresholds (typically any patient on prednisolone >5 mg for >3 months). Stopping prednisolone abruptly is dangerous (adrenal insufficiency) and not indicated here as the RA benefit justifies the dose.

Glucocorticoid-induced osteoporosis: any long-term steroid dose causes bone loss (most rapid in first 6 months). Prevent with: (1) Calcium 1000-1200 mg/day + Vitamin D 800-1000 IU/day for ALL patients; (2) Bisphosphonate (alendronate/risedronate) if FRAX threshold exceeded or prednisolone >5 mg for >3 months. Assess FRAX score at baseline and at 12 months. Bisphosphonate therapy is standard of care.

Glucocorticoid-induced osteoporosis (GIOP) occurs with any dose for >3 months. Mandatory prevention: calcium + vitamin D for all long-term steroid users; add bisphosphonate if high fracture risk (FRAX >10%) or prednisolone >5 mg for >3 months. Never stop steroids abruptly (adrenal axis suppression). Bisphosphonates (alendronate, risedronate) are proven effective for GIOP prevention.

Correct. This presentation is giant cell arteritis (GCA) with vision threat — one of the few true rheumatologic emergencies. Visual symptoms (amaurosis fugax or frank visual loss) indicate ischaemic optic neuropathy from occlusion of the posterior ciliary artery. Without immediate high-dose corticosteroids, the patient risks permanent blindness — the untreated eye frequently follows the first affected eye within days. High-dose IV methylprednisolone (500-1000 mg/day) must be started IMMEDIATELY, before or concurrently with temporal artery biopsy. Biopsy remains positive for 2-4 weeks after starting steroids — do NOT delay treatment to wait for biopsy. Low-dose prednisolone (15 mg) is for uncomplicated PMR, not GCA with visual involvement.

GCA emergencies: jaw claudication + temporal headache + visual symptoms = urgent ophthalmic referral + immediate IV methylprednisolone 500-1000 mg daily x 3 days. Do NOT wait for biopsy. TAB positive for 2-4 weeks post-steroid. Switch to prednisolone 60 mg/day orally after pulse. Permanent visual loss occurs within hours if untreated. PMR occurs in 40-60% of GCA patients; GCA occurs in 15-30% of PMR patients.

GCA with visual symptoms is a rheumatologic emergency. Immediate IV methylprednisolone (500-1000 mg/day x 3 days) must be given before permanent ischaemic optic neuropathy and blindness occur. Temporal artery biopsy confirms diagnosis but must NOT delay treatment — biopsy remains positive for 2-4 weeks after steroid initiation. 15 mg prednisolone is for PMR without visual involvement; GCA with visual symptoms requires immediate high-dose IV steroids.

Correct. When xanthine oxidase inhibitors (allopurinol, febuxostat) are insufficient or not tolerated, uricosuric agents are the alternative class. Probenecid and benzbromarone increase renal urate excretion by blocking tubular urate reabsorption (URAT1 transporter). They are less effective when eGFR <30 mL/min and increase urolith risk, so urine alkalinisation and adequate hydration are needed. In patients with CKD G3b (eGFR 45), they can still be used with caution. Pegloticase (pegylated uricase, IV monthly) is reserved for severe tophaceous gout refractory to all oral agents. Colchicine has no urate-lowering action. Indomethacin and methotrexate do not lower uric acid.

Urate-lowering therapy hierarchy: (1) Allopurinol (first-line, titrate to SUA <6.0); (2) Febuxostat (if allopurinol intolerant or insufficient); (3) Uricosurics — probenecid, benzbromarone (less effective eGFR <30); (4) Pegloticase IV (severe refractory tophaceous gout). Never start or stop ULT during an acute attack. Always provide colchicine prophylaxis for the first 3-6 months of ULT initiation.

Gout pharmacology: xanthine oxidase inhibitors (allopurinol, febuxostat) reduce urate synthesis; uricosurics (probenecid, benzbromarone) increase renal urate excretion via URAT1 blockade. Uricosurics are less effective in severe CKD (<30 mL/min) and increase stone risk. Colchicine and NSAIDs treat acute attacks — they do not lower uric acid. Methotrexate has no role in gout. Pegloticase IV is reserved for severe refractory tophaceous gout.

Correct. Anti-Scl-70 (anti-topoisomerase I) is the characteristic antibody in diffuse cutaneous systemic sclerosis (dcSSc). The 5 hallmark features of systemic sclerosis are captured by CREST: Calcinosis, Raynaud, oEsophageal dysmotility, Sclerodactyly, Telangiectasia — but dcSSc has more widespread skin involvement and is associated with anti-Scl-70. Limited cutaneous SSc (lcSSc) is associated with anti-centromere antibody. The two life-limiting complications requiring annual monitoring are: (1) Pulmonary arterial hypertension (PAH) — echocardiogram annually; and (2) Interstitial lung disease (ILD) — HRCT and pulmonary function tests (DLCO decline is an early marker). Scleroderma renal crisis (sudden hypertension + AKI) requires captopril as treatment of choice.

Systemic sclerosis antibodies: anti-Scl-70 (topoisomerase I) = diffuse SSc + ILD; anti-centromere = limited SSc (CREST) + PAH. Annual surveillance: echocardiography for PAH + DLCO/PFT for ILD. Scleroderma renal crisis = sudden hypertension + oliguria/AKI — captopril is specific treatment (NOT general antihypertensives). GI involvement (dysmotility, malabsorption) is managed with prokinetics, antibiotics for SIBO.

Anti-Scl-70 = diffuse systemic sclerosis. Annual monitoring for two life-limiting complications: PAH (echocardiogram) and ILD (DLCO on PFTs + HRCT). Limited SSc (CREST syndrome) is associated with anti-centromere antibody and has higher PAH risk. Scleroderma renal crisis = ACE inhibitor (captopril) is treatment of choice — not general hypotensive agents.

Correct. SLE pregnancies are high-risk regardless of remission status, requiring specialist care. Risks include: SLE flare during pregnancy or postpartum, pre-eclampsia (especially with antiphospholipid antibodies), preterm birth, foetal growth restriction, and foetal loss. Hydroxychloroquine is safe in pregnancy and should be CONTINUED — it reduces the risk of flare and neonatal lupus. Anti-Ro/SSA antibody is particularly important: it can cross the placenta and cause neonatal lupus including congenital heart block (3rd-degree AV block) — requires foetal cardiac monitoring from 16-28 weeks. Antiphospholipid antibodies increase thrombosis and pregnancy loss risk and require low-dose aspirin ± LMWH.

SLE pregnancy management: (1) Continue hydroxychloroquine throughout (proven safe, reduces flare); (2) Stop mycophenolate, cyclophosphamide, methotrexate, leflunomide 3 months before conception; (3) Screen for anti-Ro/SSA and anti-La/SSB — if positive, foetal echocardiography 16-28 weeks for congenital heart block; (4) Screen for antiphospholipid antibodies — if positive, low-dose aspirin ± LMWH; (5) Prednisolone and azathioprine are acceptable if needed.

SLE and pregnancy: hydroxychloroquine is SAFE and should be CONTINUED — it reduces flare risk. Anti-Ro/SSA antibody = neonatal lupus risk + congenital heart block (requires foetal echocardiography). Anti-phospholipid antibodies = thrombosis + recurrent pregnancy loss. SLE pregnancies are ALWAYS high-risk, even in remission. Teratogenic SLE drugs to stop: mycophenolate, cyclophosphamide, methotrexate, leflunomide.

Correct. Reactive arthritis is an immune-mediated sterile inflammatory arthritis — the organism is NOT in the joint. Antibiotics (doxycycline or azithromycin for Chlamydia; or appropriate agents for enteric triggers) treat the triggering infection but do NOT resolve the arthritis, which is driven by an immune response to microbial antigens processed elsewhere. NSAIDs are the primary treatment for the arthritis. Sulfasalazine may be added for persistent or refractory cases. Systemic corticosteroids are used for severe acute attacks. HLA-B27 positivity (~80% in reactive arthritis) identifies those at higher risk of developing chronic spondyloarthropathy.

Reactive arthritis: sterile inflammatory arthritis triggered by genitourinary (Chlamydia) or enteric (Salmonella, Shigella, Campylobacter, Yersinia) infection. Organism is NOT in the joint (distinguish from septic arthritis). Treat the trigger infection with antibiotics; treat the arthritis with NSAIDs. Classic triad: arthritis + urethritis + conjunctivitis (can't see, can't pee, can't bend the knee). HLA-B27 positive in ~80%. Risk of chronicity and ankylosing spondylitis development.

Reactive arthritis = sterile joint inflammation triggered by a remote infection (Chlamydia, Salmonella, etc.). The bacteria are NOT in the joint. Antibiotics treat the triggering infection only and do not cure the arthritis. Primary arthritis treatment: NSAIDs. Sulfasalazine for persistent cases. HLA-B27 positivity predicts risk of chronic/recurrent spondyloarthropathy course.