• Reiter’s syndrome, also referred to as reactive arthritis (ReA), is a rheumatoid factor (RF) seronegative spondyloarthropathy with associated ocular inflammation that is precipitated by genitourinary or gastrointestinal infections.
– Classic triad of sterile arthritis, urethritis, and conjunctivitis
• It is the most common inflammatory polyarthritis in young men.
• Incidence is about 3.5 cases per 100,000 per year.
– Epidemiologic studies differ in reported prevalence and incidence rates of causative agents, perhaps due to true epidemiologic variation, selection bias, or sampling errors (1).
• Frequency of HLA-B27 in ReA is 70–90% (of the seronegative spondyloarthropathies, only ankylosing spondylitis has a higher frequency of HLA-B27 positivity).
– Prevalence of reactive arthritis may be significantly increased in those with HIV; in sub-Saharan Africa it is 12 times higher (2).
• Measures to prevent genital and sexually transmitted disease:
– Chlamydia is the most common cause of reactive arthritis in Western countries (42–69%) (3).
• Measures to prevent gastrointestinal infection:
– Enteric bacteria such as shigella, salmonella, campylobacter, and Ureaplasma urealyticum are common pathogens worldwide.
• The pathogenesis involves an exaggerated immune response to bacterial antigens.
• Post-urogenital ReA:
– Chlamydia takes on a “persistent state” within host tissues, an alternative life cycle that avoids host immune response (3).
– Interferon (IFN)-γ concentration is lower in HLA-B27-positive patients, contributing to persistence of infected cells which act as depots stimulating sustained inflammation.
• Post-enteric ReA:
– Degraded particles of the bacterial envelope alone may persist in host tissues, creating long-lasting immune response.
An immunologic response to an infectious organism in an individual with genetic predisposition (∼75% are HLA-B27-positive) (4)[B]
COMMONLY ASSOCIATED CONDITIONS
See “General Prevention.”
• Ophthalmic manifestations (60%) (5):
– Conjunctivitis (a feature of early disease)
– Non-granulomatous anterior uveitis (NGAU) in 20–40%; typically unilateral (7% bilateral) (3)[B]
– Keratitis (4%)
– Cystoid macular edema (rare)
– Multifocal choroiditis (rare)
• Symptoms generally appear within 1–3 weeks from the inciting genitourinary or gastrointestinal infection:
– Mild constitutional symptoms such as low-grade fever and malaise
– Urogenital: Dysuria, frequency, discharge
– Musculoskeletal: Myalgias (early), swelling and pain of the large joints
– Ophthalmic: Decreased vision, pain, injection, photophobia
• Asymmetric, acute oligoarthritis affecting large joints
• Mucocutaneous lesions:
– Circinate balanitis, cervicitis, or painless oral ulcers
• Keratoderma blennorrhagicum
DIAGNOSTIC TESTS & INTERPRETATION
• Erythrocyte sedimentation rate
• C-reactive protein
• Urethra, cervix, or throat cultures
• Chlamydia PCR
• HLA-B27 genetic marker
MRI of large joints
• Synovial joint fluid aspiration (classically culture negative)
• Ankylosing spondylitis
• Inflammatory bowel disease-associated arthritis
• Psoriatic arthritis
• Gonococcal arthritis
• Lyme disease
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Juvenile rheumatoid arthritis (Still’s disease)
• Gouty arthritis
• If still present, treat the inciting infection with appropriate antibiotic therapy.
• Topical uveitis treatment:
– Prednisolone acetate 1%, 1 drop q1–2 hours (slow taper over several weeks)
– Scopolamine hydrobromide 0.25% (or similar cycloplegic agent) 1 drop b.i.d.–t.i.d.
• NSAIDs: Indomethacin SR 75 mg PO b.i.d.–t.i.d.
• Disease-modifying antirheumatic drugs (DMARDs) for chronic arthritis
– Sulfasalazine 1 g PO b.i.d.–t.i.d.
– Oral corticosteroids
– Methotrexate 7.5–15 mg PO per week
– Azathioprine 100–150 mg PO daily
– Biologics (anti-TNF agents) such as infliximab (Remicade) and adalimumab (Humira) (1)
• Rheumatology consultation
• Primary care physician
• Physical therapist
• The Spondylitis Association of America (www.spondylitis.org)
• Recurrent NGAU may lead to vision loss if not properly monitored and treated.
• Reactive arthritis may be self-limited, episodic and relapsing, or chronic and progressive (2).
– Self-limited form resolves over 3–12 months.
– 15–50% of patients develop recurrent bouts of arthritis (more common in Chlamydia-associated cases).
– 15–30% develop chronic arthritis.
– 10% of those with chronic disease develop cardiac complications such as aortic regurgitation and pericarditis.
• Vision loss
• Chronic arthritis
• Cardiac manifestations
1. Colmegna I, Espinoza LR. Recent advances in reactive arthritis. Curr Rheumatol Rep 2005;7(3):201–207.
2. Khan MA. Update on spondyloarthropathies. Ann Intern Med 2002;136(12):896–907.
3. Gerard HC, Whittum-Hudson JA, Carter JD, et al. The pathogenic role of Chlamydia in spondyloarthritis. Curr Opin Rheumatol 2010;22(4):363–367.
4. Tay-Kearney ML, Schwam BL, Lowder C, et al. Clinical features and associated systemic diseases of HLA-B27 uveitis. Am J Ophthalmol 1996;121:47–56.
5. Lee DA, Barker SM, Su WPD, et al. The clinical diagnosis of Reiter’s syndrome: Ophthalmic and non-ophthalmic aspects. Ophthalmology 1986;93:350–356.