BASICS

DESCRIPTION

• 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

EPIDEMIOLOGY

• 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).

RISK FACTORS

• HLA-B27

• HIV:

– Prevalence of reactive arthritis may be significantly increased in those with HIV; in sub-Saharan Africa it is 12 times higher (2).

GENERAL PREVENTION

• 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.

PATHOPHYSIOLOGY

• 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.

ETIOLOGY

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.”

DIAGNOSIS

• 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)

HISTORY

• 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

PHYSICAL EXAM

• Asymmetric, acute oligoarthritis affecting large joints

• Periostitis

• Sacroiliitis

• Mucocutaneous lesions:

– Circinate balanitis, cervicitis, or painless oral ulcers

• Keratoderma blennorrhagicum

DIAGNOSTIC TESTS & INTERPRETATION

Lab

• CBC

• Erythrocyte sedimentation rate

• C-reactive protein

• Urethra, cervix, or throat cultures

• Chlamydia PCR

• HIV

• HLA-B27 genetic marker

Imaging

MRI of large joints

Diagnostic Procedures/Other

• Synovial joint fluid aspiration (classically culture negative)

DIFFERENTIAL DIAGNOSIS

• 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

TREATMENT

MEDICATION

First Line

• 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.

Second Line

• 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)

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• Ophthalmologist

• Rheumatology consultation

• Primary care physician

• Physical therapist

PATIENT EDUCATION

• The Spondylitis Association of America (http://www.spondylitis.org)

PROGNOSIS

• 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.

COMPLICATIONS

• Vision loss

• Chronic arthritis

• Cardiac manifestations

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