INFECTIOUS ARTHRITIS & JOINT DISORDERS Bone & Soft Tissue Pathology Dr. Lilian Bosire --- GENERAL PRINCIPLES Microorganisms can reach joints by: - Haematogenous
INFECTIOUS ARTHRITIS & JOINT DISORDERS Bone & Soft Tissue Pathology Dr. Lilian Bosire --- GENERAL PRINCIPLES Microorganisms can reach joints by: - Haematogenous dissemination (most common) - Direct inoculation (trauma, surgery) - Contiguous spread from soft tissue abscess or osteomyelitis Key point: Cartilage has limited regenerative capacity unlike bone — rapid joint destruction from infection can cause permanent deformity if not treated promptly. --- 1. SUPPURATIVE (BACTERIAL) ARTHRITIS Acute bacterial joint infection — almost always haematogenous in adults. Causative Organisms by Age Age Group Organism --- --- Neonates Contiguous spread from epiphyseal osteomyelitis; S. aureus Except gonococcal arthritis (more common in women), joint infections affect males and females equally . --- Predisposing Factors - Complement deficiencies (C5–C9 / membrane attack complex) → especially susceptible to disseminated gonococcal infection - Immunodeficiencies (congenital and acquired, e.g. HIV) - Debilitating illness - Joint trauma or pre-existing chronic arthritis - Intravenous drug use --- Clinical Features - Classic presentation: Sudden onset of acutely painful, swollen joint with restricted range of motion - Fever, leukocytosis, elevated ESR/CRP - Gonococcal arthritis: Often subacute; usually monoarticular — knee, hip, shoulder, elbow, wrist, or sternoclavicular joints; may be associated with skin pustules and tenosynovitis (classic triad) Diagnosis & Treatment - Joint aspiration → purulent fluid + organism identification = diagnostic - Gram stain and culture of synovial fluid; blood cultures - Prompt antimicrobial therapy prevents permanent joint destruction - Drainage of purulent joint may be required (surgical or repeated aspiration) --- 2. MYCOBACTERIAL ARTHRITIS (TB ARTHRITIS) - Chronic, progressive monoarticular infection caused by Mycobacterium tuberculosis - Occurs in adults; arises from adjacent osteomyelitis OR haematogenous spread from a pulmonary focus - Onset is insidious — gradually increasing pain; systemic TB symptoms (fever, night sweats, weight loss) may or may not be present Joints Affected (in order of frequency) Hips → Knees → Ankles (weight-bearing joints) Spinal TB (Pott's disease) = vertebral involvement → can cause kyphosis and cord compression Morphology - Mycobacterial seeding → confluent granulomas with caseous necrosis in synovium - Synovium grows as a pannus over articular cartilage → bone erosion along joint margins - Chronic disease → fibrous ankylosis and obliteration of joint space Diagnosis - Synovial biopsy showing caseating granulomas is more reliable than culture alone - AFB stain, Ziehl-Neelsen; culture on Lowenstein-Jensen medium (slow) - PCR for rapid confirmation - Mantoux/TST and IGRA (interferon-gamma release assay) helpful --- 3. VIRAL ARTHRITIS Common causative viruses: - Alphaviruses (e.g., Chikungunya, Ross River virus) — direct joint infection - Parvovirus B19 — especially in adults; symmetric small joint arthritis mimicking RA - Rubella — direct synovial infection; also associated with rubella vaccination - Epstein-Barr virus - Hepatitis B & C — immune complex-mediated arthritis Mechanism: Either direct viral infection of the joint (rubella, some alphaviruses) OR autoimmune reaction triggered by the infection (molecular mimicry, immune complex deposition) - Manifestations range from acute to subacute arthritis - Usually self-limiting — resolves with clearance of the infection --- 4. LYME ARTHRITIS Aetiology - Caused by the spirochete Borrelia burgdorferi - Transmitted by deer ticks of the Ixodes ricinus complex (also I. scapularis in USA) - Vector requires prolonged attachment ( 36–48 hours) for transmission Three Clinical Stages Stage Timing Manifestations --- --- --- Early localized Days after tick bite Erythema migrans (expanding "bull's eye" rash) Early disseminated Days to weeks later Multiple skin lesions, cranial nerve palsies (CN VII most common), cardiac block, meningitis Late disseminated Months after infection Lyme arthritis , encephalopathy - Arthritis now occurs in shoulders elbows ankles - Usually one or two joints at a time; migratory pattern - Initial attacks last weeks to months; may recur at new sites Diagnosis - Spirochetes identified in synovium in only 25% of arthritis cases - Serologic detection of anti-Borrelia antibodies (ELISA confirmed by Western blot) is diagnostic - Two-tier testing recommended Histology - Chronic synovitis - Synoviocyte hyperplasia - Fibrin deposition - Mononuclear cell infiltrate (especially CD4+ T cells ) - Obliterative endarteritis (vessel wall inflammation) - Severe cases: histopathology mimics rheumatoid arthritis The autoimmune component in chronic Lyme arthritis is thought to involve molecular mimicry between B. burgdorferi antigens and self-antigens, particularly in HLA-DR4 individuals — some develop antibiotic-refractory arthritis driven by immune mechanisms rather than active infection. --- 5. CRYSTAL-INDUCED ARTHRITIS Articular crystal deposits trigger inflammatory reactions → cartilage destruction. Crystal Disease --- --- Monosodium urate (MSU) Gout Calcium pyrophosphate dihydrate (CPPD) Pseudogout (chondrocalcinosis) Basic calcium phosphate (hydroxyapatite) Calcific tendinitis / Milwaukee shoulder Exogenous (prosthetic wear debris) Implant-related arthritis --- 6. GOUT Transient attacks of acute arthritis initiated by monosodium urate (MSU) crystal deposition within and around joints, driven by hyperuricemia . Primary vs Secondary Gout Primary (90%) Secondary (10%) --- --- --- Cause Unknown; multigenic; HGPRT deficiency (X-linked) Renal disease, myeloproliferative disorders, drugs Feature Gout is the major manifestation Gout secondary to another disease --- Pathogenesis of Hyperuricemia Hyperuricemia = plasma urate 6.8 mg/dL (necessary but NOT sufficient for gout) Uric acid = end product of purine catabolism via xanthine oxidase Two purine synthesis pathways: - De novo pathway — purines synthesized from non-purine precursors - Salvage pathway — free purines from diet and catabolism recycled by HGPRT Causes of hyperuricemia: - Overproduction — increased purine turnover (myeloproliferative disease, HGPRT deficiency, high purine diet) - Reduced excretion (most common, ~90%) — renal undersecretion; urate filtered at glomerulus but almost completely reabsorbed by proximal tubule; drugs (thiazides, low-dose aspirin), renal disease, alcohol - Both — alcohol (increases purine catabolism AND decreases excretion) --- Why Only 10% of Hyperuricaemics Develop Gout? Other risk factors required: - Age and duration of hyperuricemia (usually 20–30 years before first attack) - Male sex (oestrogen is uricosuric — premenopausal women protected) - Genetic predisposition (HGPRT mutations; multigenic primary gout) - Alcohol consumption - Obesity - Drugs — thiazides, loop diuretics, low-dose aspirin, ciclosporin - Dehydration , trauma, surgery (can precipitate acute attack by changing urate solubility) --- Pathogenesis of Acute Gouty Attack 1. Hyperuricemia → precipitation of MSU crystals in joints (especially cooler peripheral joints) 2. Crystals phagocytosed by macrophages → NLRP3 inflammasome activation → IL-1β release 3. IL-1β → chemokine secretion → neutrophil chemotaxis 4. Neutrophils phagocytose crystals → release LTB4, prostaglandins, free radicals, lysosomal enzymes 5. Neutrophil lysis → more crystal release → amplification loop 6. Complement activation 7. → Tissue injury and intense inflammation The attack is self-limiting because as inflammation resolves, rising temperature and pH increase urate solubility, crystals dissolve. --- Morphology of Gout (1) Acute Arthritis - Dense neutrophilic infiltrate in synovium and synovial fluid - Needle-shaped urate crystals in small clusters in synovium and within neutrophil cytoplasm - Crystals are negatively birefringent under polarized light (yellow when parallel to compensator) - Oedematous, congested synovium with scatter