Rheumatology Inflammation Conference

Key questions

1. Q1What are the four categories of arthritis?

   Mechanical, inflammatory, crystalline and infectious. Deciding the category is the first step in every case.
2. Q2How does mechanical (osteoarthritis) pain behave?

   Worse with activity, better with rest; morning stiffness under 30 minutes; bony swelling of DIP/PIP (Heberden/Bouchard) and thumb CMC; X-ray shows osteophytes and joint-space narrowing.
3. Q3A man with bilateral nagging great-toe pain, worse with activity, no redness or warmth, and high uric acid — gout?

   No — mechanical (osteoarthritis). Crystalline arthritis is acute, intermittent, severe, red and warm; a high uric acid alone does not make it gout.
4. Q4How does rheumatoid arthritis present?

   Symmetric small-joint (wrists, MCPs) and ankle synovitis, morning stiffness >1 hour, RF and anti-CCP positive; X-ray shows regional (periarticular) osteopenia and erosions.
5. Q5How does dermatomyositis present?

   Heliotrope rash (eyelids), cheek rash, periungual/nailbed changes, proximal weakness (hips, neck flexors, biceps), dysphonia/dysphagia, ↑ CPK, +ANA. Over age 50: ~10% associated cancer.
6. Q6How does lupus present, and what signals nephritis?

   Young woman: Raynaud, photosensitive rash, arthralgia with long morning stiffness, fatigue, mild cytopenias, ANA high. Nephritis: proteinuria, RBC casts, edema, new hypertension, low complement, high anti-dsDNA; biopsy shows "lumpy-bumpy" immune complexes.
7. Q7How does polymyalgia rheumatica present?

   Over 50 (usually >60): bilateral shoulder and hip girdle pain and stiffness worse in the morning, very high ESR/CRP, RF/CCP negative, often mild anemia/thrombocytosis; dramatic response to moderate-dose prednisone (10–20 mg).
8. Q8How does axial spondyloarthritis present?

   Young adult with inflammatory back pain: morning stiffness improving with activity and NSAIDs; sacroiliitis on MRI; ↓ lumbar flexion on Schober test (may be masked by hypermobility); associated IBD and uveitis.
9. Q9How does psoriatic arthritis present?

   Psoriasis (scalp, behind ears, gluteal cleft, umbilicus), nail pitting/onycholysis ("fungus" that won't heal), dactylitis, DIP involvement, RF negative; patterns include asymmetric oligoarthritis and arthritis mutilans.
10. Q10How does granulomatosis with polyangiitis present?

    Recurrent sinusitis, saddle-nose deformity, lacrimal gland swelling, lung findings, glomerulonephritis (RBC casts, ↑ creatinine), c-ANCA / anti-PR3.
11. Q11How does sarcoidosis present?

    Uveitis with iris synechiae, purple raised facial rash (lupus pernio), arthritis, hilar lymphadenopathy on CXR, hypercalcemia; non-caseating granulomas.
12. Q12How does Sjögren differ from GPA with a swollen lacrimal gland?

    Sjögren: exocrine dysfunction (dry eyes/mouth), ANA, SSA/SSB, RF, polyclonal gammopathy; primary or secondary (with RA/SLE). GPA: destructive sinus/nose, lung and kidney disease, c-ANCA.
13. Q13What kind of vasculitis is GPA?

    A small-vessel (sometimes medium-vessel) necrotizing granulomatous vasculitis, c-ANCA/PR3.

Key questions

1. Q14How do glucocorticoids work, and what are their toxicities?

   Broad anti-inflammatory/immunosuppressive (↓ NF-κB, ↓ cytokines, ↓ phospholipase A2). Toxicities: glucose intolerance/diabetes, central obesity, acne, ↑ lipids, cataracts, osteoporosis and fractures, avascular necrosis (hips, knees, shoulders), infection.
2. Q15How does cyclophosphamide work, and what are its toxicities?

   Alkylating agent (cross-links DNA). Oral daily is more potent than periodic IV. Toxicities: high infection risk, hemorrhagic cystitis and bladder cancer (acrolein), premature ovarian failure/infertility. Give mesna to protect the bladder; low-dose "Euro-Lupus" IV protocols preferred.
3. Q16How does mycophenolate mofetil work?

   Reversible inhibitor of inosine monophosphate dehydrogenase → blocks de novo guanosine synthesis; T and B cells depend on this pathway (other cells use salvage).
4. Q17How does azathioprine work?

   Purine analog converted to 6-MP and 6-thioguanine, incorporated into DNA; targets lymphocytes; mainly a maintenance drug after cyclophosphamide.
5. Q18What newer agents treat lupus?

   Calcineurin inhibitors (cyclosporine, tacrolimus, voclosporin) reduce proteinuria; belimumab (BLyS/BAFF) helps joints, skin and kidneys; anifrolumab (type I interferon receptor blocker) helps skin and joints; rituximab for refractory disease; anti-TNF is usually avoided (can induce lupus).
6. Q19How does hydroxychloroquine help lupus long term?

   Probably reduces antigen presentation by macrophages (↑ lysosomal pH, ↓ TLR signaling); maintained in almost all lupus patients.
7. Q20What is methotrexate's role outside RA?

   Lupus skin and joints (not kidneys), GPA limited disease and maintenance, sarcoidosis, psoriatic arthritis; unsafe with advanced renal disease.

Key questions

1. Q21How is mild lupus (rash, oral ulcers, arthralgia) treated?

   Hydroxychloroquine (± short-term low-dose prednisone).
2. Q22How is lupus nephritis treated?

   Induction: glucocorticoids plus mycophenolate mofetil or cyclophosphamide; maintenance MMF or azathioprine; continue hydroxychloroquine; add-ons belimumab or calcineurin inhibitors. Steroids alone do not improve renal survival.
3. Q23How is dermatomyositis treated?

   Glucocorticoids first, with steroid-sparing agents (methotrexate, azathioprine, mycophenolate), IVIG or rituximab for refractory disease; screen for cancer.
4. Q24How is RA treated in the conference case?

   Early DMARD (methotrexate), treat to target, add biologics (anti-TNF, abatacept, rituximab, tocilizumab) or JAK inhibitor if needed.
5. Q25How is polymyalgia rheumatica treated?

   Moderate-dose prednisone (10–20 mg) with dramatic response; taper; watch for giant cell arteritis; tocilizumab is used for GCA.
6. Q26How is axial spondyloarthritis treated?

   NSAIDs first; then anti-TNF (e.g., adalimumab) or IL-17 inhibitors. Monoclonal anti-TNFs also treat associated IBD and uveitis.
7. Q27How is psoriatic arthritis treated?

   NSAIDs, methotrexate, then biologics: anti-TNF, IL-17, IL-12/23 (skin), T-cell co-stimulation blockade, or JAK inhibitors.
8. Q28How is GPA treated?

   Induction: glucocorticoids plus cyclophosphamide or rituximab (± plasma exchange for pulmonary hemorrhage; methotrexate for limited disease). Maintenance: rituximab every 6 months, methotrexate (if GFR ≥50) or azathioprine (if GFR <50). Consider PCP prophylaxis.
9. Q29How is sarcoidosis treated?

   Glucocorticoids, with methotrexate as a steroid-sparing agent (also HCQ, anti-TNF monoclonals for refractory disease).

Key questions

1. Q30What is the general approach to each case?

   Pattern recognition → differential diagnosis → accurate diagnosis → confirmatory testing → treatment (empiric vs specific) → measure success and toxicity.
2. Q31What are the goals of treating autoimmune inflammatory disease?

   Reduce pain, dysfunction/damage and disability, and avoid complications — weighing the consequences of the disease against those of treatment.
3. Q32Case: 59-year-old with 15–30 min stiffness, thumb-base and PIP/DIP pain worse with knitting. Diagnosis and approach?

   Osteoarthritis (mechanical). No true disease-modifying drug — analgesics/NSAIDs, exercise, joint protection; measure function and pain.
4. Q33Case: 24-year-old with cheek/eyelid/nailbed rash, proximal weakness, nasal voice, CPK 2000. Diagnosis and therapy?

   Dermatomyositis → glucocorticoids (plus steroid-sparing agent); follow CPK and strength; watch steroid toxicity; long-term treatment needed.
5. Q34Case: 35-year-old flight attendant, wrist/ankle/knuckle stiffness for hours, RF and anti-CCP positive, periarticular osteopenia. Diagnosis and therapy?

   Rheumatoid arthritis → early DMARD (methotrexate), treat to target with DAS/ACR/RAPID3, add biologic if needed.
6. Q35Case: 20-year-old with Raynaud, photosensitive rash, 2-hour stiffness, ANA 1:1280, normal kidneys. Diagnosis and first therapy?

   Lupus → hydroxychloroquine.
7. Q36Same patient a year later: proteinuria, RBC casts, low complement, high anti-dsDNA, cytopenias, new hypertension. Therapy?

   Lupus nephritis → prednisone plus mycophenolate mofetil (or cyclophosphamide); maintain hydroxychloroquine.
8. Q37That patient later develops hip pain; MRI shows a necrotic femoral head. Principal cause?

   Her therapy — corticosteroids → avascular necrosis.
9. Q38Case: 68-year-old with 3 months of neck, shoulder and hip pain, worse in the morning, ESR 60, CRP 15, RF/ANA negative. Diagnosis and therapy?

   Polymyalgia rheumatica → prednisone 10–20 mg with dramatic response; monitor ESR/CRP and steroid toxicity.
10. Q39Case: 29-year-old dancer with morning back pain improving with activity and naproxen, hypermobile, normal Schober, MRI sacroiliitis. Diagnosis, therapy and later GI complication?

    Axial spondyloarthritis (hypermobility masks the Schober test) → adalimumab (anti-TNF). After stopping, bloody diarrhea with neutrophilic colitis = inflammatory bowel disease (associated with SpA; anti-TNF had been treating it).
11. Q40Case: 35-year-old with non-healing "toenail fungus," dandruff, scalp/gluteal plaques, 3-hour stiffness of fingers and toes. Diagnosis?

    Psoriatic arthritis (CASPAR: psoriasis, nail lesions, dactylitis, RF negative) → NSAIDs/MTX → anti-TNF or IL-17/IL-12/23 biologics.
12. Q41Case: 55-year-old with lacrimal gland swelling, recurrent sinusitis, saddle nose, RBC casts, c-ANCA/PR3. Diagnosis and therapy?

    Granulomatosis with polyangiitis (not Sjögren) → glucocorticoids + rituximab or cyclophosphamide; maintenance rituximab/MTX/AZA; PCP prophylaxis.
13. Q42Case: 40-year-old with bilateral uveitis with synechiae, purple facial rash, PIP swelling, mild hypercalcemia, hilar nodes. Diagnosis and therapy?

    Sarcoidosis → systemic steroids with methotrexate as a steroid-sparing agent.
14. Q43What are the options for an acute gout attack?

    High-dose short-acting NSAID until the attack resolves, colchicine, or a glucocorticoid (oral or an intramuscular long-acting injection). Start urate-lowering therapy (allopurinol) only after the flare.