6.2 Inflammatory Arthropathies & Crystal-Induced Diseases

Crystal-Induced & Inflammatory Arthropathies

Evaluating joint pain requires distinguishing acute non-inflammatory joint disorders from systemic inflammatory polyarthritis and life-threatening intra-articular infections. Prompt arthrocentesis and synovial fluid analysis are required for any acute warm, swollen monoarthritis.

Crystal-Induced Arthropathies: Gout vs. Pseudogout

Gout is a microcrystalline arthropathy caused by monosodium urate (MSU) deposition in joint spaces following chronic hyperuricemia (serum uric acid > 6.8 mg/dL). Primary triggers for acute flares include high-purine meals, alcohol ingestion, dehydration, surgical stress, and medications that alter renal uric acid excretion (thiazide and loop diuretics, low-dose aspirin).

• Clinical Presentation: Podagra (acute severe pain, erythema, and warmth of the first MTP joint) is the initial manifestation in > 50% of patients. Chronic untreated gout leads to tophi (painless aggregations of urate crystals surrounded by giant-cell granulomatous inflammation in the olecranon bursa, Achilles tendon, or ear pinna).
• Synovial Fluid Analysis: Reveals needle-shaped crystals exhibiting strong negative birefringence under polarized light microscopy (crystals appear yellow when parallel to the red compensator filter).
• Pharmacotherapy: Acute flares are treated with high-dose NSAIDs (indomethacin), oral colchicine (inhibits neutrophil microtubule polymerization; avoid if CrCl < 30 mL/min), or corticosteroids. Chronic urate-lowering therapy with allopurinol (a xanthine oxidase inhibitor) is indicated for patients with >= 2 acute flares per year, tophi, or chronic kidney disease. Target serum uric acid is < 6.0 mg/dL. HLA-B*5801 allele screening is required prior to initiating allopurinol in high-risk populations (Han Chinese, Korean, and Thai ancestry) to prevent Stevens-Johnson syndrome. Urate-lowering agents should not be initiated during an acute flare unless anti-inflammatory coverage is established.

Pseudogout (Calcium Pyrophosphate Deposition [CPPD] Disease) involves intra-articular deposition of calcium pyrophosphate crystals:

• Clinical Presentation: Acute inflammatory monoarthritis or oligoarthritis affecting large weight-bearing joints, most commonly the knee (> 50% of cases) or wrist. Plain radiographs reveal chondrocalcinosis (punctate, linear calcifications within articular cartilage or menisci).
• Synovial Fluid Analysis: Reveals rhomboid-shaped crystals exhibiting weak positive birefringence under polarized light (crystals appear blue when parallel to the compensator).
• Underlying Associations: CPPD is strongly linked to hereditary hemochromatosis (iron overload), primary hyperparathyroidism, hypomagnesemia, and hypothyroidism. Management of acute flares mirrors gout (NSAIDs, colchicine, steroids).

Rheumatoid Arthritis & Osteoarthritis

Rheumatoid Arthritis (RA) is a chronic, systemic autoimmune disease marked by invasive synovial pannus formation leading to articular cartilage and bone destruction:

• Clinical Presentation: Symmetric polyarthritis affecting small hand and foot joints, specifically the proximal interphalangeal (PIP), metacarpophalangeal (MCP), and wrist joints. Distal interphalangeal (DIP) joints are characteristically spared. Patients report morning stiffness lasting > 1 hour that improves with joint movement. Classic deformities include swan-neck deformity (PIP hyperextension with DIP flexion) and boutonnière deformity (PIP flexion with DIP hyperextension).
• Diagnostic Biomarkers: Anti-cyclic citrullinated peptide (anti-CCP) antibodies possess superior specificity (> 95%) compared to Rheumatoid Factor (RF; IgM antibody directed against the Fc region of human IgG).
• Extra-Articular Manifestations: Rheumatoid nodules, interstitial lung disease, pericarditis, episcleritis, and Felty syndrome (triad of severe RA, splenomegaly, and neutropenia with ANC < 1,500/µL). RA frequently involves the cervical spine; subluxation of the atlantoaxial joint can cause subacute spinal cord compression. Mandatory cervical spine plain radiographs (flexion/extension views) are required prior to elective endotracheal intubation in long-standing RA.
• Treatment Protocol: Methotrexate (folate antagonist) is the mandatory first-line DMARD. Co-administration of daily folic acid reduces gastrointestinal toxicity and stomatitis. Baseline CBC, liver function tests, and chest radiograph are required. Biologic DMARDs targeting TNF-alpha (infliximab, adalimumab, etanercept) are added if non-biologic DMARDs fail. Screening for latent tuberculosis with PPD or IGRA and Hepatitis B is mandatory prior to initiating TNF-alpha inhibitors.

Osteoarthritis (OA) is a progressive, non-inflammatory degenerative joint disease caused by biomechanical wear and cartilage loss:

• Clinical Presentation: Asymmetric involvement of weight-bearing joints (hips, knees) and hand joints (DIP and PIP joints, first CMC joint). Features Heberden nodes (bony enlargement at DIP joints) and Bouchard nodes (bony enlargement at PIP joints). Morning stiffness is brief (< 30 minutes), and joint pain worsens with activity and improves with rest.
• Radiographic Hallmarks: Asymmetric joint space narrowing, subchondral sclerosis, osteophytes, and subchondral bone cysts.

Seronegative Spondyloarthropathies

Seronegative spondyloarthropathies are strongly associated with the HLA-B27 class I MHC gene and negative testing for RF and anti-CCP. Shared features include axial skeletal involvement, enthesitis (Achilles tendonitis), and dactylitis ("sausage digits").

• Ankylosing Spondylitis (AS): Affects young males (< 40 years) presenting with chronic dull low back pain and morning stiffness (> 30 minutes) that improves with physical exercise but not with rest. Plain radiographs demonstrate bilateral sacroiliitis progressing to vertebral syndesmophytes and fusion ("bamboo spine"). The most common extra-articular manifestation is acute anterior uveitis (occurring in 25-30% of patients), presenting with unilateral eye pain, photophobia, and ciliary flush. First-line therapy is high-dose continuous NSAIDs; refractory cases require TNF-alpha inhibitors.
• Psoriatic Arthritis: Occurs in up to 30% of psoriasis patients. Characterized by dactylitis, nail pitting, DIP joint involvement, and radiologic "pencil-in-cup" deformities.
• Reactive Arthritis: Post-infectious autoimmune triad of urethritis, conjunctivitis, and arthritis ("can't see, can't pee, can't climb a tree"). Triggered 1 to 4 weeks following Chlamydia trachomatis genitourinary infection or GI infections (Campylobacter, Shigella, Salmonella, Yersinia).

Septic Arthritis & Joint Aspiration

Septic arthritis is an orthopedic emergency caused by hematogenous inoculation of the joint space. Staphylococcus aureus is the most common etiology overall; Neisseria gonorrhoeae affects sexually active young adults (presenting with tenosynovitis, migratory polyarthralgias, and painless pustular skin lesions). Physical examination reveals a swollen, erythematous joint locked by severe pain during passive motion. Synovial fluid WBC count > 50,000/µL with > 75-90% PMNs is diagnostic. Immediate management mandates IV empiric antibiotics (vancomycin ± third-generation cephalosporin) and emergency surgical joint drainage.

Diagnostic Algorithm: Acute Monoarthritis Workup

[ Acute Warm, Swollen Monoarthritis ]
                   │
                   ▼
     [ Immediate Arthrocentesis ]
                   │
       ┌───────────┴───────────┐
       ▼                       ▼
[ WBC > 50,000/µL ]     [ WBC 2,000 - 50,000/µL ]
[ > 75-90% PMNs   ]     │
       │                ├─► Needle / Neg Birefringence ──► Gout (MSU)
       ▼                ├─► Rhomboid / Pos Birefringence ─► Pseudogout (CPPD)
[ Septic Arthritis ]    └──► Non-crystal, Anti-CCP (+) ──► Rheumatoid Arthritis
       │
       ├─► Emergency Joint Drainage (Surgical / Arthroscopic)
       └─► Empiric IV Vancomycin (+ Ceftriaxone if Gonococcal risk)

Synovial Fluid Classification Matrix