{"title": "Chapter 12: Rheumatological and Musculoskeletal Disorders", "flashcards": [{"q": "What are the 2010 ACR/EULAR classification criteria for rheumatoid arthritis?", "a": "Scoring system (score ≥6/10 required): Joint involvement (1–5 small joints = 2pts; >10 including small = 5pts); Serology (low-positive RF/anti-CCP = 2pts; high-positive = 3pts); Acute phase reactants (CRP or ESR = 1pt); Duration (≥6 weeks = 1pt). Anti-CCP antibody has ~95% specificity for RA."}, {"q": "Name four extra-articular manifestations of rheumatoid arthritis.", "a": "Pulmonary (ILD, pleural effusion, nodules, pulmonary hypertension, Caplan syndrome in coal miners); ocular (keratoconjunctivitis sicca, episcleritis, scleritis); cardiovascular (accelerated atherosclerosis, pericarditis, myocarditis); haematological (Felty's syndrome — RA + splenomegaly + neutropaenia; anaemia of chronic disease); vasculitis; peripheral neuropathy; amyloidosis."}, {"q": "What is the mechanism of action of methotrexate in RA?", "a": "Methotrexate inhibits dihydrofolate reductase (DHFR), impairing folate metabolism and reducing purine/pyrimidine synthesis in rapidly dividing cells (inflammatory cells). In RA, its primary anti-inflammatory effect is mediated via increased extracellular adenosine, which has anti-inflammatory properties. Folic acid supplementation (5 mg once weekly) reduces toxicity (mucositis, hepatotoxicity, cytopaenia) without reducing efficacy."}, {"q": "Define the 2019 EULAR/ACR classification criteria for SLE.", "a": "Requires positive ANA (titre ≥1:80 by HEp-2) as entry criterion, then additive scoring across 7 domains: Constitutional; Haematological; Neuropsychiatric; Mucocutaneous; Serosal; Musculoskeletal; Renal. Plus Immunological domain (anti-dsDNA, anti-Sm, antiphospholipid antibodies, complement). Score ≥10 classifies SLE."}, {"q": "What is the BASDAI and what score indicates active ankylosing spondylitis requiring escalation?", "a": "Bath Ankylosing Spondylitis Disease Activity Index (BASDAI): 6 questions scored 0–10 measuring fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, morning stiffness (duration and severity). Average of 2 morning stiffness questions included. BASDAI ≥4 despite NSAIDs indicates active disease warranting biological therapy (TNF inhibitor or IL-17 inhibitor)."}, {"q": "Name three features of gout on joint aspiration.", "a": "Negatively birefringent, needle-shaped monosodium urate (MSU) crystals under polarised light; turbid/purulent fluid; PMN pleocytosis (WBC often >50,000/µL); positive Gram stain/culture excludes concurrent septic arthritis (which can coexist). Serum urate is unhelpful acutely (may be normal or low during an acute attack)."}, {"q": "What is the FRAX tool?", "a": "Fracture Risk Assessment Tool (FRAX) calculates 10-year probability of major osteoporotic fracture and hip fracture, using age, sex, BMI, previous fragility fracture, parental hip fracture, smoking, alcohol, corticosteroid use, secondary osteoporosis, and femoral neck T-score (if available). FRAX ≥10% for major fracture OR ≥3% for hip fracture (varies by country) is used to guide treatment decisions."}, {"q": "What are the indications for immediate joint aspiration in a hot, swollen joint?", "a": "Every hot, swollen monoarthritis should be aspirated to exclude septic arthritis — which cannot be reliably distinguished from gout or pseudogout clinically. Failure to diagnose septic arthritis promptly leads to irreversible joint destruction. Crystal-induced arthritis and haemarthrosis are diagnosed on aspiration. Aspiration also provides therapeutic drainage in infection."}, {"q": "Name three disease-modifying antirheumatic drugs (DMARDs) used in RA.", "a": "Conventional synthetic DMARDs (csDMARDs): methotrexate (anchor drug), sulfasalazine, hydroxychloroquine, leflunomide. Biologic DMARDs (bDMARDs): anti-TNF (adalimumab, etanercept, infliximab, certolizumab, golimumab); anti-IL-6 (tocilizumab, sarilumab); anti-CD20 (rituximab); CTLA-4Ig (abatacept). Targeted synthetic DMARDs (tsDMARDs): JAK inhibitors (baricitinib, tofacitinib, upadacitinib)."}, {"q": "What is fibromyalgia and how is it diagnosed?", "a": "Fibromyalgia is a centralised pain syndrome characterised by chronic widespread pain, fatigue, non-restorative sleep, and cognitive difficulties. 2016 ACR criteria: Widespread Pain Index (WPI) ≥7 + Symptom Severity Scale (SSS) ≥5; OR WPI 4–6 + SSS ≥9; symptoms present ≥3 months; no alternative diagnosis. Investigations are normal. Treatment: aerobic exercise (most evidence), CBT, duloxetine, amitriptyline."}], "quiz": [{"q": "Which biologic agent is first-line for RA failing methotrexate?", "opts": ["IL-1 inhibitor", "Anti-TNF agent (adalimumab or etanercept) — or tocilizumab (IL-6 inhibitor) or abatacept as alternatives; JAK inhibitors for those unable to take biologics", "Anti-CD52 antibody (alemtuzumab)", "B-cell depleting agent rituximab as first biologic"], "ans": 1, "exp": "NICE TA715 (2021): after failure of two conventional DMARDs including methotrexate, biologic DMARDs are indicated. Anti-TNF agents (adalimumab, etanercept, certolizumab, golimumab, infliximab biosimilars) are first-line biologics in RA. Tocilizumab, abatacept, rituximab, and JAK inhibitors are alternatives. Methotrexate is co-prescribed with biologics to reduce immunogenicity."}, {"q": "What radiographic finding is pathognomonic of ankylosing spondylitis?", "opts": ["Punched-out lytic lesions", "Bamboo spine (bridging syndesmophytes from ossification of the annulus fibrosus) and sacroiliitis on plain X-ray; MRI shows early bone marrow oedema before X-ray changes", "Periosteal reaction", "Chondrocalcinosis"], "ans": 1, "exp": "AS X-ray findings: sacroiliitis (bilateral, symmetrical — mandatory for modified New York criteria); square vertebrae ('romanus lesion'); syndesmophytes (vertical ossification of outer annulus fibrosus, eventually forming 'bamboo spine'). MRI detects bone marrow oedema (active sacroiliitis) up to 8–10 years before X-ray changes, enabling earlier diagnosis per ASAS criteria."}, {"q": "Which antibody is most specific for Sjögren's syndrome?", "opts": ["ANA", "Anti-Ro/SSA and anti-La/SSB antibodies", "Anti-dsDNA", "Anti-CCP"], "ans": 1, "exp": "Anti-Ro/SSA is present in ~75% and anti-La/SSB in ~50% of primary Sjögren's syndrome patients. Both are relatively specific for Sjögren's and SLE. Anti-Ro is associated with neonatal lupus (congenital heart block) when present in a pregnant woman. Minor salivary gland biopsy showing focal lymphocytic sialadenitis (focus score ≥1) confirms diagnosis."}, {"q": "What is the most common cause of acute monoarthritis in a sexually active 25-year-old?", "opts": ["Gout", "Reactive arthritis (formerly Reiter's syndrome) or gonococcal arthritis", "Rheumatoid arthritis", "Pseudogout"], "ans": 1, "exp": "In a young sexually active adult with acute monoarthritis, gonococcal arthritis (disseminated gonococcal infection — DGI) is an important diagnosis: migratory polyarthralgia followed by monoarthritis ± tenosynovitis ± skin lesions (painless pustules). Reactive arthritis follows STI or GI infection. Gout is uncommon before age 30 except in secondary causes. NAAT swabs from urethra/cervix/pharynx/rectum are needed."}, {"q": "What is the mechanism of action of hydroxychloroquine in SLE?", "opts": ["TNF-alpha inhibition", "Inhibition of TLR signalling by blocking Toll-like receptor 7/9 in lysosomes, reducing type I interferon production and antigen presentation; reduces disease flares and thrombotic risk", "Direct B-cell depletion", "COX-2 inhibition"], "ans": 1, "exp": "Hydroxychloroquine (HCQ) accumulates in lysosomes, raising lysosomal pH and inhibiting TLR7 and TLR9 signalling by nucleic acid antigens, reducing type I interferon production — a key driver of SLE pathogenesis. HCQ reduces flares, organ damage accrual, thrombosis, and mortality in SLE. Annual ophthalmological screening for retinal toxicity is required."}, {"q": "What is the first-line management of acute gout?", "opts": ["Start allopurinol during the acute attack", "High-dose NSAIDs (naproxen, indomethacin) or colchicine (500 µg BD–TDS) or oral prednisolone; rest and ice; do NOT start allopurinol during acute attack", "IV corticosteroids only", "Aspirin 75 mg"], "ans": 1, "exp": "Acute gout: NSAIDs (e.g. naproxen 500 mg BD) or colchicine (500 µg 2–4× daily) or oral prednisolone 30–35 mg for 5 days. Avoid aspirin (competes with urate excretion at low doses). Do NOT start urate-lowering therapy (allopurinol, febuxostat) during an acute attack — precipitates or prolongs the attack. Start ULT ≥2–4 weeks after attack resolution."}, {"q": "What is the target serum urate for patients on urate-lowering therapy (ULT) for gout?", "opts": ["<420 µmol/L (7 mg/dL)", "<360 µmol/L (6 mg/dL) for most patients; <300 µmol/L (5 mg/dL) for tophaceous gout", "<600 µmol/L", "<480 µmol/L"], "ans": 1, "exp": "BSR and EULAR recommend target serum urate <360 µmol/L for most patients on ULT (allopurinol, febuxostat), and <300 µmol/L for tophaceous gout. Allopurinol dose should be titrated to achieve this target (starting 100 mg OD, increasing monthly). In CKD, allopurinol should be started at lower doses (50 mg OD) and increased cautiously."}, {"q": "Which anti-TNF drug is CONTRAINDICATED in patients with moderate-severe heart failure (NYHA III–IV)?", "opts": ["Adalimumab", "Infliximab (and etanercept at high doses — both contraindicated in NYHA III–IV HF; adalimumab also requires caution)", "Tocilizumab", "Rituximab"], "ans": 1, "exp": "Anti-TNF agents (infliximab, etanercept) have been associated with worsening heart failure, particularly at higher doses. They are contraindicated in NYHA Class III–IV HF. Adalimumab carries a similar warning. Tocilizumab (anti-IL-6) and abatacept can be used with caution. JAK inhibitors require cardiovascular risk assessment (ORAL Surveillance trial data)."}, {"q": "What is lupus nephritis and which class carries the worst prognosis?", "opts": ["Class I (minimal mesangial) — worst prognosis", "Class III (focal) or Class IV (diffuse proliferative) — most severe, requiring intensive immunosuppression; Class V (membranous) causes nephrotic syndrome", "Class II (mesangial) — requires immediate dialysis", "Class VI (advanced sclerosis) — responds to steroids"], "ans": 1, "exp": "ISN/RPS histological classes: I (minimal mesangial), II (mesangial proliferative), III (focal proliferative <50% glomeruli), IV (diffuse proliferative ≥50% glomeruli — worst prognosis), V (membranous LN), VI (advanced sclerosis). Class III/IV: induction with high-dose corticosteroids + MMF or cyclophosphamide (Euro-Lupus regimen); maintenance with MMF or azathioprine."}, {"q": "What distinguishes osteoarthritis from rheumatoid arthritis on examination?", "opts": ["OA affects small hand joints symmetrically", "OA causes Heberden's (DIP) and Bouchard's (PIP) nodes, bony hard swelling, worse in afternoon/evening; RA causes symmetrical soft MCP/PIP swelling, morning stiffness >1 hour, sparing DIP joints, systemic features", "RA causes crepitus; OA does not", "OA causes elevated inflammatory markers"], "ans": 1, "exp": "OA: DIP (Heberden's nodes) and PIP (Bouchard's nodes) involvement, bony hard swellings, minimal inflammation, pain worst with activity and evening, crepitus, no systemic features, normal inflammatory markers. RA: MCP and PIP involvement, soft boggy swelling, morning stiffness >1 hour, symmetrical, spares DIP joints, elevated CRP/ESR/positive serology, extra-articular features."}, {"q": "What is reactive arthritis (formerly Reiter's syndrome) and what triggers it?", "opts": ["Septic arthritis from direct bacterial invasion", "Sterile inflammatory arthritis occurring 1–4 weeks after GI (Salmonella, Shigella, Yersinia, Campylobacter) or urogenital (Chlamydia trachomatis) infection in HLA-B27 positive individuals; classic triad: arthritis, urethritis, conjunctivitis ('can't see, can't pee, can't climb a tree')", "Autoimmune arthritis from unknown trigger", "Viral arthritis from parvovirus"], "ans": 1, "exp": "Reactive arthritis is HLA-B27 associated in ~75% of cases. Lower limb large joint oligoarthritis (knee, ankle), sacroiliitis, enthesitis (Achilles tendinitis, plantar fasciitis), circinate balanitis, keratoderma blennorrhagica (hyperkeratotic rash on palms/soles), mucosal ulcers. NSAIDs first-line; sulfasalazine/methotrexate for persistent disease. Most resolve within 6 months; 20% develop chronic SpA."}, {"q": "What is the mechanism of action of TNF-alpha in rheumatoid arthritis pathogenesis?", "opts": ["TNF-alpha only causes bone erosion", "TNF-alpha is a pro-inflammatory cytokine that activates NF-κB signalling in synoviocytes and macrophages, upregulating matrix metalloproteinases (bone/cartilage destruction), stimulating synovial angiogenesis, increasing leukocyte adhesion/migration, and promoting osteoclast activation (RANKL upregulation)", "TNF-alpha only affects T cells", "TNF-alpha suppresses the immune system in RA"], "ans": 1, "exp": "TNF-alpha is a key driver of RA synovitis: promotes synovial fibroblast and macrophage activation; induces IL-1, IL-6, IL-8 production; upregulates RANK-L (osteoclast activation → bony erosion); increases VEGF (angiogenesis perpetuating synovial proliferation). Anti-TNF agents (adalimumab, etanercept, infliximab, certolizumab, golimumab) block these pathways, achieving ACR20/50/70 responses and preventing structural damage."}, {"q": "What is the 'treat-to-target' (T2T) principle in rheumatoid arthritis management?", "opts": ["Treat with fixed DMARD doses and never change", "Define a specific treatment target (remission or low disease activity measured by DAS28/SDAI/CDAI) and adjust therapy at regular intervals (every 1–3 months) until the target is achieved — evidence shows superior outcomes vs conventional management", "Treat symptoms alone without monitoring scores", "Only applicable in early RA"], "ans": 1, "exp": "T2T strategy: set a clear target (remission: DAS28 <2.6 or SDAI ≤3.3; or LDA: DAS28 <3.2 for those where remission is impractical); measure disease activity at every visit; escalate therapy if target not met at 3 months. This strategy (TICORA, BeST trials) significantly reduces joint damage, disability, and long-term work loss compared to usual care. Remission rates improved from <20% to >50% with T2T approaches."}, {"q": "What is polymyalgia rheumatica (PMR) and how is it distinguished from giant cell arteritis (GCA)?", "opts": ["PMR and GCA are identical conditions", "PMR: aching stiffness of shoulder/pelvic girdle, ESR >40, CRP elevated, age >50, responds dramatically to prednisolone 15–25 mg. GCA: same demographics + cranial symptoms (temporal headache, jaw claudication, scalp tenderness, visual loss from AION — medical emergency); overlapping in ~50%; GCA requires higher prednisolone doses (40–60 mg) ± IV methylprednisolone for vision loss", "PMR affects joints; GCA affects muscles only", "GCA never causes visual loss"], "ans": 1, "exp": "PMR and GCA are related conditions (both affect elderly, high inflammatory markers, respond to steroids, are granulomatous vasculitides). Key distinction: GCA involves large vessels (temporal artery, aorta, its branches) causing ischaemia — jaw claudication and visual loss are emergencies (AION causes sudden irreversible visual loss). Temporal artery biopsy confirms GCA. Tocilizumab (anti-IL-6) reduces steroid dose in GCA."}, {"q": "What are the ACR/EULAR 2019 classification criteria entry criterion for SLE?", "opts": ["Anti-dsDNA alone", "Positive ANA (antinuclear antibody) at titre ≥1:80 by HEp-2 cell IFA (or equivalent positive test) — the obligate entry criterion before additive scoring of domain criteria", "Anti-Sm antibody", "Complement C3 reduction"], "ans": 1, "exp": "The 2019 EULAR/ACR SLE criteria require positive ANA (≥1:80 by HEp-2 IFA) as mandatory entry criterion — without this, SLE cannot be classified regardless of domain scores. ANA is highly sensitive (>95%) but not specific. After ANA-positivity confirmed, weighted scores across seven clinical domains and one immunological domain are summed; total ≥10 classifies SLE."}, {"q": "What is enthesitis and which conditions are most commonly associated?", "opts": ["Inflammation within joint cartilage", "Inflammation at the enthesis — the site where tendons, ligaments, or joint capsules insert into bone; characteristic of seronegative spondyloarthropathies (AS/axSpA, psoriatic arthritis, reactive arthritis, IBD-associated arthritis). Common sites: Achilles tendon insertion, plantar fascia, patella tendon, greater trochanter", "An extra-articular feature of RA only", "Inflammation of the joint synovium"], "ans": 1, "exp": "Enthesitis is a hallmark of SpA — driven by IL-17 and TNF-alpha at entheseal sites rich in fibrocartilage and innervation. Clinical: heel pain (Achilles enthesitis, plantar fasciitis), knee pain (patella or quadriceps tendon), costochondritis. Assessment: Leeds Enthesitis Index (LEI) in psoriatic arthritis. Anti-IL-17A (secukinumab, ixekizumab) has superior efficacy for enthesitis and skin in SpA vs anti-TNF."}, {"q": "What is the role of DEXA scan in osteoporosis management?", "opts": ["DEXA is only for diagnostic purposes", "DEXA (dual-energy X-ray absorptiometry) measures bone mineral density (BMD) at lumbar spine and femoral neck; T-score ≤-2.5 = osteoporosis, -1 to -2.5 = osteopaenia, ≥-1 = normal; used with FRAX to assess 10-year fracture risk and guide treatment decisions; repeat scanning monitors response to bisphosphonate therapy (every 2–5 years)", "T-score is not used in clinical practice", "DEXA only measures spinal density"], "ans": 1, "exp": "DEXA T-score: BMD compared to young healthy reference population. Z-score: compared to age-matched peers (low Z-score suggests secondary osteoporosis — investigate). FRAX tool integrates clinical risk factors ± femoral neck BMD to calculate 10-year probability of major fragility fracture and hip fracture. Treatment threshold (UK) typically: FRAX major fracture ≥10% or prior fragility fracture. Bisphosphonates (alendronate, risedronate) first-line; denosumab, romosozumab for high-risk."}, {"q": "Which biologic agent is first-line for psoriatic arthritis with predominant axial disease?", "opts": ["Methotrexate (effective for axial SpA)", "TNF inhibitor (adalimumab, certolizumab, etanercept) or IL-17A inhibitor (secukinumab, ixekizumab) after NSAID failure — NICE recommends TNF inhibitors first-line, with IL-17 inhibitors as alternatives", "IL-12/23 inhibitor (ustekinumab)", "JAK inhibitor first-line for axial disease"], "ans": 1, "exp": "For psoriatic arthritis with axial involvement (sacroiliitis or spinal inflammation), NSAIDs are first-line. If inadequate: TNF inhibitors or IL-17 inhibitors (secukinumab, ixekizumab) are recommended — evidence supports efficacy in axial SpA. Ustekinumab (IL-12/23) has less evidence for axial disease. JAK inhibitors (tofacitinib, upadacitinib) are alternatives when biologics are contraindicated. Methotrexate does NOT treat axial disease in SpA."}, {"q": "What is the 'sicca syndrome' and which conditions cause it?", "opts": ["Generalised skin dryness from eczema", "Dry eyes (xerophthalmia) and dry mouth (xerostomia) from reduced lacrimal and salivary gland secretion; primary cause: primary Sjögren's syndrome; secondary: RA, SLE, systemic sclerosis, sarcoidosis; other causes: anticholinergic drugs, radiation, ageing, HIV, HCV", "Excessive tearing and salivation", "Mouth ulcers in IBD"], "ans": 1, "exp": "Sicca syndrome assessment: Schirmer's test (<5 mm wetting in 5 min = abnormal); rose Bengal/fluorescein staining for keratoconjunctivitis sicca; unstimulated salivary flow; minor salivary gland biopsy for focal lymphocytic sialadenitis. Anti-Ro/SSA + anti-La/SSB serology. Management: artificial tears, hydroxypropyl methylcellulose; pilocarpine eye drops/oral (cholinergic agonist); saliva substitutes; hydroxychloroquine for systemic features."}, {"q": "What is the most significant long-term complication of ankylosing spondylitis?", "opts": ["Joint replacement requirement", "Spinal fusion ('bamboo spine') causing progressive loss of spinal mobility + flexion deformity; extra-articular: anterior uveitis (25–40% — recurrent), aortic regurgitation, cardiac conduction defects, pulmonary fibrosis (apical), and amyloidosis; increased risk of spinal fracture (through ankylosed spine)", "Renal failure", "Peripheral joint destruction as in RA"], "ans": 1, "exp": "AS complications: progressive spinal ankylosis impairs respiratory excursion (reduced chest expansion) and puts patients at risk of spinal fracture through the rigid fused spine (often at cervicothoracic junction after minor trauma — unstable fracture, high cord injury risk). Anterior uveitis (acute, unilateral, recurrent) occurs in 25–40%. Regular ophthalmological follow-up, cardiovascular screening (aortic root dilation), and DEXA for osteoporosis are important."}]}