Reactive Arthritis

Reactive arthritis is precipitated by antecedent GI or genitourinary infections and manifests as an asymmetric sterile oligoarthritis, typically of the lower extremities.

It is frequently associated with enthesitis.

Extra-articular manifestations are common and include urethritis, conjunctivitis, uveitis, keratoderma blennorrhagicum, and mucocutaneous lesions.

Reactive arthritis occurs most commonly in young men and is associated with HLA-B27 in 80% of White patients and 50–60% of Black patients.

Diagnostic Essentials

• Oligoarthritis, conjunctivitis, urethritis, keratoderma blennorrhagicum, and mouth ulcers.
• Usually follows dysentery or a sexually transmitted infection.
• HLA-B27-positive in 50-80% of patients.

Clinical Findings

Symptoms and Signs

Most cases of reactive arthritis develop within 1–4 weeks after either a GI infection (usually with Shigella, Salmonella, Yersinia, or Campylobacter) or a sexually transmitted infection (with Chlamydia trachomatis or perhaps Ureaplasma urealyticum). Whether the inciting infection is sexually transmitted or dysenteric does not affect the subsequent manifestations but does influence the gender ratio. The spectrum of pathogens known to cause reactive arthritis is broadening to include Mycobacterium, Staphylococcus, and SARS-CoV-2.

Synovial fluid from affected joints is culture-negative.

A clinically indistinguishable syndrome can occur without an apparent antecedent infection, suggesting that subclinical infection can precipitate reactive arthritis or that there are other, as yet unrecognized, triggers.

The arthritis is most commonly asymmetric and frequently involves the large weight-bearing joints (knee and ankle); sacroiliitis or ankylosing spondylitis is observed in at least 20% of patients, especially after frequent recurrences.

Systemic symptoms including fever and weight loss are common at the onset of disease.

The mucocutaneous lesions may include balanitis, stomatitis, and keratoderma blennorrhagicum, indistinguishable from pustular psoriasis.

Involvement of the fingernails in reactive arthritis mimics psoriatic changes.

When present, conjunctivitis is mild and occurs early in the disease course.

Anterior uveitis, which can develop at any time in HLA-B27–positive patients, is a more clinically significant ocular complication.

Carditis and aortic regurgitation may occur.

While most signs of the disease disappear within days or weeks, the arthritis may persist for several months or become chronic.

Recurrences involving any combination of the clinical manifestations are common and are sometimes followed by permanent sequelae, especially in the joints (eg, articular destruction).

Imaging

Radiographic signs of permanent or progressive joint disease may be seen in the sacroiliac and peripheral joints.

Differential Diagnosis

Gonococcal arthritis can initially mimic reactive arthritis, but the marked improvement after 24–48 hours of antibiotic administration in gonococcal arthritis and the culture results distinguish the two disorders.

Rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis must also be considered.

By causing similar oral, ocular, and joint lesions, Behçet disease may mimic reactive arthritis. In reactive arthritis, however, the oral lesions are typically painless, in contrast to those of Behçet disease.

Treatment

NSAIDs have been the mainstay of therapy.

Antibiotics given at the time of a nongonococcal sexually transmitted infection reduce the chance that the individual will develop this disorder. For chronic reactive arthritis associated with chlamydial infection, a randomized trial demonstrated that 6 months of rifampin (300 mg orally twice daily) in combination with either doxycycline (100 mg orally twice daily) or azithromycin (500 mg orally daily for 5 days then twice weekly) was more effective than placebo.

Patients who do not respond to NSAIDs may respond to sulfasalazine or methotrexate.

For those patients with recent-onset disease that is refractory to NSAIDs and these DMARDs, anti-TNF agents, which are effective in the other spondyloarthropathies, may be effective.