Spondylitis

Reactive Arthritis

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Reactive Arthritis, Reiter's Syndrome, Reiter's Disease, Circinate Balanitis, Urethro-oculo-articular Syndrome

  • See Also
  1. Spondyloarthropathy
  2. Poststreptococcal Reactive Arthritis
  3. Viral Arthritis
  • Definitions
  1. Reactive Arthritis
    1. Inflammatory Arthritis onset within 6 weeks after triggering infection (enteric, urologic)
    2. Associated with Spondyloarthropathy and aseptic inflammatory Polyarthritis
  • Epidemiology
  1. Most common inflammatory Polyarthritis in young men
    1. Incidence: as high as 33 in 100,000 males
  2. Gender
    1. More common in men by ratio of 9:1 to 5:1
  3. Age of onset as early as 13 years
  • Pathophysiology
  1. Inflammatory Arthritis onset within 6 weeks after triggering infection (enteric, urologic)
    1. Excessive, autoimmune response to Bacterial Antigens
    2. Associated with HLA-B27 Genotype in 66-80% of patients
  2. Reactive Arthritis is the modern name for a disease previously known as Reiter's Syndrome
    1. Condition was first described by Hans Reiter in 1916
      1. Reference case was Prussian Soldier with Diarrhea
    2. Hans Reiter was also a nazi war criminal
      1. Performed cruel human experiments on Prisoners (including infecting them with Typhus)
  • Causes
  • Infectious Agents in Reactive Arthritis
  1. Diarrheal Illness
    1. Shigella flexneri
    2. Shigella dysenteriae
    3. Clostridium difficile
    4. Salmonella typhimurium
    5. Salmonella enteritidis
    6. Yersinia enterocolitica
    7. Campylobacter jejuni
  2. Nonspecific Urethritis
    1. Chlamydia Trachomatis
    2. Ureaplasma Urealyticum
  3. Immunodeficiency
    1. Human Immunodeficiency Virus (HIV)
      1. Reactive Arthritis may be initial presentation of HIV
  • Signs
  1. Arthritis onset 1-4 weeks after GI or GU infection
  2. Classic Clinical Triad (infrequently present, affects <33% of patients)
    1. Arthritis
    2. Conjunctivitis
    3. Non-Gonococcal Urethritis
  3. Asymmetric Oligoarticular Arthritis (2-4 joints)
    1. Affects lower extremities most commonly
    2. Large Knee Effusion
    3. Dactylitis (Sausage-shaped fingers and toes)
      1. Also seen in Psoriatic Arthritis
    4. Enthesitis (ligament, tendon insertion inflammation)
      1. Achilles Tendonitis
      2. Plantar Fasciitis
      3. Patellofemoral Syndrome
    5. Axial Spondyloarthropathy
      1. Low Back Pain from inflammatory Sacroiliitis
    6. Other musculoskeletal involvement
      1. Anterolateral ribs
      2. Pubic Symphysis
      3. Iliac crest
  4. Constitutional symptoms
    1. Weight loss
    2. Fever up to 102 F
  5. Gastrointestinal (precedes Arthritis by 1-4 weeks)
    1. Acute Diarrhea
  6. Genitourinary (precedes Arthritis by 1-4 weeks)
    1. Urethritis (90%)
    2. Cystitis
    3. Hematuria
    4. Hydronephrosis
    5. Cervicitis or Vulvitis in women
    6. Circinate Balanitis (10-20% of cases) in men
      1. Shallow, painless gray-border ulcer of glans penis
      2. More common in uncircumcised men
  7. Skin changes
    1. Nail Abnormality
      1. Nail findings similar to Psoriasis (Psoriatic Nail Pitting, Psoriatic Onycholysis)
    2. Keratoderma blenorrhagica
      1. Hyperkeratotic, waxy Papules and Plaques on the palms and the plantar foot surface
      2. Similar to lesions in Pustular Psoriasis
    3. Painless, shallow Oral Ulcers
      1. Tongue ulceration
      2. Lip Ulceration
      3. Pharyngeal ulceration
      4. Palate and Buccal mucosa ulcerations (similar to the glans ulcers, Circinate Balanitis)
  8. Eye changes
    1. Conjunctivitis (50% of patients)
    2. Acute Anterior Uveitis (in up to 37% of cases)
  9. Cardiovascular changes (rare)
    1. Aortitis
    2. Aortic Insufficiency
    3. Conduction abnormality with potential Heart Block
  • Differential Diagnosis
  1. See Spondyloarthropathy
  2. Poststreptococcal Reactive Arthritis
  3. Viral Arthritis
  4. Ankylosing Spondylitis
  5. Colitic Arthritis (associated with Ulcerative Colitis)
  6. Gonococcal Arthritis (NeisseriaGonorrhea)
  7. Systemic Lupus Erythematosus
  8. Lyme Disease
  9. Psoriatic Arthritis (Associated with Psoriasis)
  10. Rheumatic Fever
  11. Rheumatoid Arthritis
  12. Juvenile Rheumatoid Arthritis (Still's Disease)
  13. Gouty Arthritis
  • Labs
  1. HIV Test
  2. Complete Blood Count
    1. Anemia
  3. Acute Phase reactants
    1. Erythrocyte Sedimentation Rate (ESR) increased
    2. C-Reactive Protein (CRP) increased
  4. HLA-B27
    1. Positive status associated with more severe disease
  5. Joint Fluid exam
    1. Synovial Fluid WBC: 15,000 to 30,000 per mm3
    2. Neutrophils predominate on differential (>66%)
    3. Normal Joint FluidGlucose
    4. No Synovial Fluid Crystals on Polarized Microscopy
  • Diagnosis
  • Reactive Arthritis
  1. Major Criteria
    1. Arthritis with at least 2 findings
      1. Asymmetrical
      2. Monoarthritis or Oligoarthritis
      3. Leg involvement
    2. Preceding symptomatic infection with at least one finding starting 3 days to 6 weeks before Arthritis onset
      1. Enteritis (Diarrhea for at least 1 day)
      2. Urethritis (Dysuria or Urethral discharge for at least 1 day)
  2. Minor Criteria
    1. Evidence of triggering infection (e.g. Chlamydia PCR, enteric pathogen diagnosis by NAT)
    2. Evidence of persistent synovial infection (e.g. immunohistology, PCR)
  3. Interpretation
    1. Definite Diagnosis
      1. Both major criteria and one minor criteria met
    2. Probable Diagnosis
      1. Both major criteria met OR
      2. One major and one minor criteria
  4. References
    1. Selmi (2014) Autoimmun Rev 13(4-5): 546-9 +PMID: 24418301 [PubMed]
  • Precautions
  1. Rule-out Septic Arthritis as cause!
    1. Obtain Synovial Fluid as above
    2. Consider Antistreptolysin-O Antibody Test
  1. First Line Medications
    1. NSAIDs
      1. Ibuprofen or Naproxen
      2. May consider Indomethacin initially (e.g. 25-50 mg bid-tid) instead for refractory symptoms on other nsaids
    2. Intra-articular Corticosteroid Injection
      1. Consider for symptomatic large joint effusions
  2. Antibiotic indications
    1. Doxycycline 100 mg orally twice daily for 10-14 days
      1. Indicated for suspected Chlamydia etiology
      2. Prior longer course (2-3 months) for Reactive Arthritis did not show benefit
      3. Putschky (2006) Ann Rheum Dis 65(11):1521-4 +PMID: 17038453 [PubMed]
  3. Second and third line agents with variable efficacy (consult rheumatology)
    1. TNF Inhibitors (monoclonal antibodies)
    2. Persistent disease
      1. Sulfasalazine 1 gram PO bid to tid
    3. Chronic Disability (avoid in HIV Infection)
      1. Methotrexate 7.5 to 25 mg per week
      2. Azathioprine (Imuran) 100 to 150 mg orally daily
  • Course
  1. Self-limited: Resolves over 3-12 months
  2. Chronic Arthritis may develop in up to 30% of cases
  • References
  1. Tak Yan Yu in Ruddy (2001) Kelley's Rheum, p. 1055-67
  2. Arnett in Klippel (1997) Primer Rheumatic, p. 184-88
  3. Barth (1999) Am Fam Physician 60:499-507 [PubMed]
  4. Kataria (2004) Am Fam Physician 69:2853-60 [PubMed]
  5. Kim (2026) Am Fam Physician 114(3): 262-70 [PubMed]
  6. Kirchner (1995) Postgrad Med 97(3): 111-22 [PubMed]