Epidemiology

• Genetic predisposition and association with HLA-B27
• Commonly affects young men

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Etiology

Postinfectious autoimmune disorder

• Posturethritis: after infection with Chlamydia (common) or Ureaplasma urealyticum
• Postenteritis: after infection with Shigella, Yersinia, Salmonella, or Campylobacter

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Pathophysiology

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Clinical features

Tip

The clinical manifestations are caused by immune complexes involving bacterial antigens. However, it does not represent disseminated infection, and joint aspirates are sterile (ie, it is a ‘reactive’ not infectious arthritis).

• Recent UTI or GI infections
• Musculoskeletal symptoms
  • Oligoarthritis (sometimes polyarthritis)
    • Acute onset
    • Often asymmetrical with a migratory character
    • Occurs predominantly in the lower extremities
  • Sacroiliitis
  • Enthesitis
  • Dactylitis
• Extra‑articular symptoms
  • Ocular: conjunctivitis, anterior uveitis
  • Genital: urethritis, cervicitis, prostatitis
  • Dermal: keratoderma blennorrhagicum, circinate balanitis
  • Oral ulcers
• Symptoms from preceding infection
  • Diarrhea
  • Urogenital tract symptoms (dysuria, pelvic pain, prostatitis)

Mnemonic

Classic triad of reactive arthritis (seen in approximately one-third of affected individuals): “can’t see (conjunctivitis), can’t pee (urethritis), can’t climb a tree (arthritis)”.

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Differential Diagnostics

BRANCH 1: ACUTE (< 6 weeks)

• 1a: Acute Monoarthritis (1 Joint)
  • RED FLAG: Suspect Septic Arthritis? (Fever, chills, severe pain, erythema, warmth, ↓ROM)
    • YES → URGENT ACTION: Hospitalize, Ortho/Rheum consult, Arthrocentesis STAT (Cell count & diff, Gram stain, Culture, Crystals), Blood cultures, CBC, ESR/CRP. Start empiric IV antibiotics AFTER aspiration.
  • Suspect Crystal Arthropathy (Gout/Pseudogout)? (Sudden onset, severe pain, prior episodes, triggers)
    • YES → Arthrocentesis (Look for MSU/CPPD crystals), Serum Uric Acid (can be normal acutely), CBC, ESR/CRP, X-ray (may show chondrocalcinosis in pseudogout).
  • Suspect Trauma/Hemarthrosis? (History of injury, rapid swelling)
    • YES → X-ray (rule out fracture), Consider Arthrocentesis (bloody fluid), CBC (if bleeding disorder suspected).
  • Other Possibilities: Early presentation of oligo/polyarthritis, Lyme disease (rarely mono).
• 1b: Acute Oligo/Polyarthritis (≥2 Joints)
  • Inflammatory Features Present?
    • YES → Consider:
      • Viral Arthritis: (e.g., Parvovirus B19, Hepatitis B/C, Rubella, HIV) - often symmetric, may have rash/flu-like prodrome. Workup: Viral serologies, LFTs, HIV test, CBC, ESR/CRP.
      • Reactive Arthritis: (Post-GI/GU infection, often asymmetric oligoarthritis, +/- urethritis, conjunctivitis, enthesitis) - Workup: Stool/Urine culture (if indicated), Chlamydia testing, HLA-B27, ESR/CRP.
      • Early Systemic Rheumatic Disease: (RA, SLE, PsA, SpA) - Workup: ESR/CRP, RF, Anti-CCP, ANA, Uric Acid, HLA-B27 (if SpA suspected), X-rays.
      • Serum Sickness: (Drug reaction) - History, rash, fever.
      • Lyme Disease: (Tick exposure history) - Lyme serology (may be negative early), ESR/CRP.
      • Acute Rheumatic Fever: (Post-strep infection, migratory polyarthritis - rare in developed nations) - ASO titre, Throat culture, ECG.
  • Non-inflammatory Features Dominant?
    • YES → Consider: Uncommon acutely unless widespread OA flare or multiple joints injured. Workup: X-rays, ESR/CRP (usually normal).

BRANCH 2: CHRONIC (> 6 weeks)

• 2a: Chronic Monoarthritis (1 Joint)
  • Inflammatory Features Present?
    • YES → Consider:
      • Chronic Infection: (TB, Fungal, Lyme) - Workup: Arthrocentesis (AFB/fungal stain/culture, Lyme PCR), PPD/IGRA, Chest X-ray, ESR/CRP, Synovial biopsy may be needed.
      • Chronic Crystal Arthropathy: (Gout/Pseudogout) - Workup: Arthrocentesis (crystals), Uric Acid, X-ray.
      • Spondyloarthritis (SpA): (Esp. knee/hip) - Workup: HLA-B27, ESR/CRP, Imaging (X-ray, MRI of SI joints if back pain).
      • Pauciarticular JIA: (In younger patients).
  • Non-inflammatory Features Dominant?
    • YES → Consider:
      • Osteoarthritis (OA): (Commonest cause) - Workup: X-ray (joint space narrowing, osteophytes), ESR/CRP (usually normal).
      • Avascular Necrosis (AVN): (Esp. hip, knee, shoulder; risk factors: steroids, alcohol) - Workup: X-ray (may be normal early), MRI is diagnostic.
• 2b: Chronic Oligo/Polyarthritis (≥2 Joints)
  • Inflammatory Features Present?
    • YES → Consider Systemic Rheumatic Diseases:
      • Rheumatoid Arthritis (RA): (Symmetric small joints, hands/feet, morning stiffness >1hr, nodules) - Workup: ESR/CRP, RF, Anti-CCP (specific), X-rays (erosions), +/- Ultrasound/MRI.
      • Spondyloarthropathies (SpA): (Incl. Ankylosing Spondylitis, Psoriatic Arthritis, Reactive, Enteropathic) - Often asymmetric, axial involvement (back pain), enthesitis, dactylitis, +/- skin/eye/GI symptoms. Workup: ESR/CRP, HLA-B27, X-rays (SI joints, spine), Skin/Nail exam, +/- MRI.
      • Connective Tissue Diseases: (SLE, Scleroderma, Polymyositis) - Look for specific extra-articular features (rash, Raynaud’s, photosensitivity, organ involvement). Workup: ESR/CRP, ANA, ENA panel, C3/C4, CK, Urinalysis.
      • Chronic Crystal Arthropathy: (Tophaceous Gout, CPPD) - Workup: Arthrocentesis, Uric Acid, X-rays.
      • Vasculitis: (Less common cause of arthritis) - Look for systemic signs (purpura, neuropathy, organ dysfunction). Workup: ANCA, ESR/CRP, Urinalysis, Biopsy (if indicated).
  • Non-inflammatory Features Dominant?
    • YES → Consider:
      • Generalized Osteoarthritis (OA): (Hands - DIP/PIP/CMC1, Knees, Hips, Spine) - Workup: X-rays, ESR/CRP (normal).
      • Fibromyalgia: (Widespread pain, fatigue, sleep disturbance, tender points - not true joint inflammation) - Diagnosis of exclusion, often normal labs/imaging. Consider TSH, Vitamin D.

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Treatment

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Prognosis

• Resolves spontaneously within a year
• High rate of recurrence