7.2 Joint Disease, Rheumatology & Connective Tissue

Synovial Joint Structure and Why It Matters

A typical diarthrodial (synovial) joint includes: articular hyaline cartilage (type II collagen + proteoglycans, notably aggrecan), a joint cavity filled with synovial fluid (hyaluronan-rich lubricant and nutrient medium), synovial membrane (intimal lining cells and subintima with vessels), a fibrous capsule, and stabilizing ligaments. Cartilage is avascular and aneural; chondrocytes rely on diffusion from synovial fluid and subchondral bone. Synovium is highly vascular—so systemic inflammatory diseases attack synovium first, producing effusions, pannus, and secondary cartilage/bone damage. Entheses (tendon/ligament insertions) are the preferred target in seronegative spondyloarthropathies, explaining axial pain and dactylitis patterns distinct from pure synovial RA.

---

Osteoarthritis vs Rheumatoid Arthritis

Osteoarthritis (OA) is primarily a degenerative disease of cartilage with secondary bone and soft-tissue change. Mechanical stress, age, obesity (knees), prior trauma, and malalignment drive chondrocyte dysfunction, matrix degradation (MMPs, aggrecanases), fissuring, and loss of joint space. Compensatory osteophytes, subchondral sclerosis, and cysts appear. Inflammation is typically low-grade and local; systemic autoantibodies are absent. Joints: DIP (Heberden), PIP (Bouchard), first CMC, knees, hips, spine facet joints. Morning stiffness is brief (<30 minutes teaching cutoff).

Rheumatoid arthritis (RA) is a systemic autoimmune disease centered on chronic synovitis. Activated T cells, B cells/plasma cells, macrophages, and fibroblasts form pannus that invades cartilage and bone. Autoantibodies include rheumatoid factor (IgM against IgG Fc—sensitive but not specific) and anti-CCP (ACPA) (more specific). Shared epitope HLA-DR4 associations appear in many curricula. Joints: symmetric MCP, PIP, wrists; DIP usually spared (contrast OA). Prolonged morning stiffness, rheumatoid nodules (seropositive patients), and extra-articular disease (ILD, vasculitis, Felty syndrome triad in severe cases) distinguish systemic burden. Radiographs: periarticular osteopenia, marginal erosions, joint-space narrowing without osteophyte dominance.

---

Seronegative Spondyloarthropathies (HLA-B27 Cluster)

“Seronegative” means RF-negative. Shared features: HLA-B27 association, enthesitis, axial arthritis (sacroiliitis/spondylitis), asymmetric oligoarthritis, dactylitis, and extra-articular clues (uveitis, psoriasis, IBD, preceding infection).

Ankylosing spondylitis: young men classic teaching demographic; inflammatory back pain improving with activity; bilateral sacroiliitis; syndesmophytes → bamboo spine; anterior uveitis; restrictive chest expansion late.

Reactive arthritis: sterile arthritis days–weeks after GU (Chlamydia) or GI (Salmonella, Shigella, Yersinia, Campylobacter) infection; triad teaching memory of arthritis, uveitis/conjunctivitis, urethritis; keratoderma blennorrhagicum and circinate balanitis as skin/mucosal clues.

Psoriatic arthritis: skin psoriasis ± nail pitting/onycholysis; patterns include DIP-predominant disease, asymmetric oligoarthritis, arthritis mutilans, or axial disease; pencil-in-cup deformity teaching image.

IBD-associated arthritis: peripheral arthritis often tracks gut activity; axial disease may be more independent; link to Crohn/UC.

Mechanism theme: innate and adaptive responses at entheses and mucosal interfaces in genetically susceptible (HLA-B27) hosts—not RF-driven synovial pannus of RA.

---

Crystal Arthropathies: Gout vs CPPD

Gout results from tissue deposition of monosodium urate (MSU) crystals when supersaturated urate exists (overproduction or underexcretion of uric acid). Acute attacks: intense monoarthritis, classically first MTP (podagra), with fever possible—mimics septic arthritis (always consider infection). Triggers: alcohol, purine load, thiazides, cell turnover, post-op. Chronic tophaceous gout deposits chalky MSU in soft tissue. Synovial fluid: needle-shaped crystals, negatively birefringent under polarized light (yellow when parallel to compensator—mnemonic teaching). Associations: tumor lysis, Lesch–Nyhan (HGPRT deficiency) for overproduction vignettes; CKD and diuretics for underexcretion.

Calcium pyrophosphate deposition (CPPD) / pseudogout: rhomboid crystals, weakly positively birefringent. Acute mono/oligoarthritis often of the knee; chondrocalcinosis on radiographs. Associations: aging, osteoarthritis, hemochromatosis, hyperparathyroidism, hypomagnesemia—boards love secondary causes in younger-than-expected patients.

Septic arthritis remains the emergency differential for any acute hot joint—crystal disease does not exclude concurrent infection, but crystal identification explains sterile inflammatory attacks.

---

SLE: Joint and Skin Anchors

Systemic lupus erythematosus is immune-complex–mediated multi-organ autoimmunity. Joint disease is usually non-erosive arthritis (contrast RA erosions)—painful, inflammatory, often hands/knees. Skin: malar (butterfly) rash sparing nasolabial folds, discoid lesions, photosensitivity, oral ulcers. Other high-yield: cytopenias, serositis, lupus nephritis (anti-dsDNA association), neuropsychiatric lupus, Libman–Sacks endocarditis. Antibodies: ANA screening; anti-dsDNA and anti-Smith more specific; anti-histone with drug-induced lupus (hydralazine, procainamide, isoniazid classic list); antiphospholipid antibodies with thrombosis/miscarriage phenotype. Type III hypersensitivity themes dominate many organ lesions; cytopenias lean type II.

---

Scleroderma: Limited vs Diffuse

Systemic sclerosis features fibroblast activation, vasculopathy, and autoimmunity → fibrosis of skin and internal organs.

Limited cutaneous systemic sclerosis (lcSSc): skin thickening mainly distal extremities and face; CREST cluster—Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia. Antibody: anti-centromere. Pulmonary arterial hypertension is a feared late complication.

Diffuse cutaneous systemic sclerosis (dcSSc): proximal and truncal skin involvement; higher risk of early interstitial lung disease and scleroderma renal crisis (malignant-range hypertension, thrombotic microangiopathy). Antibody: anti-Scl-70 (topoisomerase I); RNA polymerase III associates with renal crisis in many teaching sources.

Raynaud phenomenon is nearly universal. GI dysmotility and reflux are common to both subsets.

---

Sjögren Syndrome

Sjögren is autoimmune destruction of exocrine glands → keratoconjunctivitis sicca and xerostomia. Primary or secondary (RA, SLE). Antibodies: anti-SSA (Ro) and anti-SSB (La). Extraglandular: arthritis, RTA (type I), increased lymphoma risk (especially MALT). Lymphocytic infiltrate of salivary glands is the histologic theme. Neonatal lupus/heart block links to maternal anti-Ro in pregnancy contexts—high-yield crossover with SLE/Sjögren serology.

---

Polymyositis and Dermatomyositis

Inflammatory myopathies present with proximal muscle weakness (rising from chair, combing hair). Polymyositis: endomysial CD8+ T-cell invasion of muscle fibers; high CK; anti-Jo-1 (anti-synthetase) associates with interstitial lung disease and mechanic’s hands. Dermatomyositis: perimysial/perivascular inflammation, complement-mediated capillary injury themes; skin findings—Gottron papules, heliotrope rash, shawl sign; adult disease associates with underlying malignancy risk (age-appropriate cancer evaluation concept). Both can show ANA positivity and myositis-specific antibodies; EMG and biopsy refine diagnosis. Overlap with antisynthetase syndrome is a modern teaching package (myositis + ILD + arthritis + fever + Raynaud + mechanic’s hands).

---

Vasculitis by Vessel Size: Mechanism Vignettes

Large-vessel vasculitis

• Giant cell (temporal) arteritis: older adults; headache, jaw claudication, scalp tenderness, risk of irreversible blindness (posterior ciliary arteries); polymyalgia rheumatica association; granulomatous inflammation of branches of carotid; elevated ESR; treat promptly when suspected.
• Takayasu arteritis: younger females; “pulseless” disease; granulomatous aortitis and major branches; claudication, BP asymmetry.

Medium-vessel vasculitis

• Polyarteritis nodosa (PAN): segmental transmural necrotizing inflammation of muscular arteries; microaneurysms (renal, mesenteric); spares lungs; hepatitis B association classic; mononeuritis multiplex, hypertension, abdominal pain after meals.
• Kawasaki disease: children; coronary artery aneurysms risk; mucocutaneous lymph node syndrome pattern (fever, conjunctivitis, strawberry tongue, rash, extremity changes, lymphadenopathy).

Small-vessel vasculitis

• Immune-complex / ANCA contexts:
  • Granulomatosis with polyangiitis (GPA, Wegener): c-ANCA/PR3; upper/lower respiratory granulomas + glomerulonephritis.
  • Microscopic polyangiitis (MPA): p-ANCA/MPO; necrotizing GN and pulmonary capillaritis without granulomas.
  • Eosinophilic GPA (Churg–Strauss): asthma, eosinophilia, p-ANCA variable; vasculitis with eosinophils.
  • IgA vasculitis (HSP): children post-URI; palpable purpura on legs/buttocks, arthritis, abdominal pain, IgA nephropathy.
  • Cryoglobulinemic vasculitis: HCV association; purpura, arthralgia, weakness; immune complexes.

---

Putting Rheumatology Vignettes Together

Approach acute monoarthritis with septic vs crystal first. Approach chronic symmetric small-joint disease with RA serology and erosions. Approach inflammatory back pain and enthesitis with HLA-B27 disease cluster. Approach multi-system disease with antibody–organ maps (SLE, scleroderma subsets, Sjögren, myositis). Approach purpura, mononeuritis, GN, or organ ischemia with vessel-size vasculitis algorithms. These pattern packages generate most MSK rheumatology points on comprehensive basic science exams.