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Reactive Arthritis

by Roy D. Altman, MD

Reactive arthritis is an acute spondyloarthropathy that often seems precipitated by an infection, usually GU or GI. Common manifestations include asymmetric arthritis of variable severity that tends to affect the lower extremities, sausage-shaped deformities of fingers or toes or both, constitutional symptoms, enthesitis, tendinitis, and mucocutaneous ulcers, including hyperkeratotic or crusted vesicular lesions (keratoderma blennorrhagicum). Diagnosis is clinical. Treatment involves NSAIDs and sometimes sulfasalazine or immunosuppressants.

Spondyloarthropathy associated with urethritis or cervicitis, conjunctivitis, and mucocutaneous lesions (previously called Reiter syndrome) is one type of reactive arthritis.


Two forms of reactive arthritis are common: sexually transmitted and dysenteric. The sexually transmitted form occurs primarily in men aged 20 to 40. Genital infections with Chlamydia trachomatis are most often implicated. Men or women can acquire the dysenteric form after enteric infections, primarily Shigella, Salmonella, Yersinia, or Campylobacter. Reactive arthritis probably results from joint infection or postinfectious inflammation. Although there is evidence of microbial antigens in the synovium, organisms cannot be cultured from joint fluid.


The prevalence of the HLA-B27 allele in patients is 63 to 96% vs 6 to 15% in healthy white controls, thus supporting a genetic predisposition.

Symptoms and Signs

Reactive arthritis can range from transient monarticular arthritis to a severe, multisystem disorder. Constitutional symptoms may include fever, fatigue, and weight loss. Arthritis may be mild or severe. Joint involvement is generally asymmetric and oligoarticular or polyarticular, occurring predominantly in the large joints of the lower extremities and in the toes. Back pain may occur, usually with severe disease. Enthesopathy (inflammation at tendinous insertion into bone—eg, plantar fasciitis, digital periostitis, Achilles tendinitis) is common and characteristic. Mucocutaneous lesions—small, transient, relatively painless, superficial ulcers—commonly occur on the oral mucosa, tongue, and glans penis (balanitis circinata). Particularly characteristic are vesicles (sometimes identical to pustular psoriasis) of the palms and soles and around the nails that become hyperkeratotic and form crusts (keratoderma blennorrhagicum). Rarely, cardiovascular complications (eg, aortitis, aortic insufficiency, cardiac conduction defects), pleuritis, and CNS or peripheral nervous system symptoms develop.

Urethritis may develop 7 to 14 days after sexual contact (or occasionally after dysentery); low-grade fever, conjunctivitis, and arthritis develop over the next few weeks. Not all features may occur, so incomplete forms need to be considered. In men, the urethritis is less painful and productive of purulent discharge than acute gonococcal urethritis and may be associated with hemorrhagic cystitis or prostatitis. In women, urethritis and cervicitis may be mild (with dysuria or slight vaginal discharge) or asymptomatic. Conjunctivitis is the most common eye lesion. It usually causes mild eye redness and grittiness, but keratitis and anterior uveitis can develop also, causing eye pain, photophobia, and tearing.


  • Typical arthritis

  • Symptoms of GI or GU infection

  • One other extra-articular feature

Reactive arthritis should be suspected in patients with acute, asymmetric arthritis affecting the large joints of the lower extremities or toes, particularly if there is tendinitis or a history of an antecedent diarrhea or dysuria. Diagnosis is ultimately clinical and requires the typical peripheral arthritis with symptoms of GU or GI infection or one of the other extra-articular features. Because these features may manifest at different times, definitive diagnosis may require several months. Serum and synovial fluid complement levels are high, but these findings are not usually diagnostic and need not be measured.

Disseminated gonococcal infection can closely simulate reactive arthritis (see Gonorrhea). Arthrocentesis may fail to differentiate them, owing to inflammatory characteristics of synovial fluid in both disorders and the difficulty of culturing gonococci from this fluid. Clinical characteristics may help; disseminated gonococcal infection tends to involve upper and lower extremities equally, be more migratory, and not cause back pain, and vesicles tend not to be hyperkeratotic. A positive gonococcal culture from blood or skin lesions helps differentiate the two disorders, but a positive culture from the urethra or cervix does not. If differentiation is still difficult, ceftriaxone may be required for simultaneous diagnosis and treatment.

Psoriatic arthritis can simulate reactive arthritis, causing similar skin lesions, uveitis, and asymmetric arthritis. However, psoriatic arthritis often affects mostly the upper extremities and especially the distal interphalangeal joints, may be abrupt in onset but may also develop gradually, causes less enthesopathy, and tends not to cause mouth ulcers or symptoms of GU or GI infection.


Reactive arthritis often resolves in 3 to 4 mo, but up to 50% of patients experience recurrent or prolonged symptoms over several years. Joint, spinal, or sacroiliac inflammation or deformity may occur with chronic or recurrent disease. Some patients are disabled.


  • NSAIDs

  • Sometimes sulfasalazine, doxycycline, azathioprine or methotrexate, or a combination

  • Supportive measures

NSAIDs (eg, indomethacin 25 to 50 mg po tid) usually help relieve symptoms. If induced by infection with C. trachomatis, doxycycline 100 mg po bid for up to 3 mo may accelerate recovery, but this is controversial. Sulfasalazine as used to treat RA may also be helpful (see Joint Disorders:Traditional disease-modifying antirheumatic drugs (DMARDs)). If symptoms are severe despite NSAIDs and sulfasalazine, azathioprine or methotrexate may be considered. Systemic corticosteroids have no proven value.

Local injection of depot corticosteroids for enthesopathy or resistant oligoarthritis may relieve symptoms. Physical therapy aimed at maintaining joint mobility is helpful during the recovery phase. Anterior uveitis is treated as usual, with corticosteroid and mydriatic eye drops to prevent scarring. Conjunctivitis and mucocutaneous lesions require only symptomatic treatment.

Key Points

  • Reactive arthritis is an acute spondyloarthropathy that typically occurs after a sexually transmitted or enteric infection.

  • Manifestations can include arthritis (usually asymmetric and involving large lower extremity joints and toes), enthesopathy, mucocutaneous lesions, conjunctivitis, and genital discharge (eg, urethritis, cervicitis).

  • Confirm the diagnosis with typical arthritic findings plus either symptoms of GU or GI infection or a characteristic extra-articular finding.

  • Treat with NSAIDs and sometimes sulfasalazine or immunosuppressants.

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