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Reactive Arthritis


Kinanah Yaseen

, MD, Cleveland Clinic

Reviewed/Revised Nov 2022
Topic Resources

Reactive arthritis is an acute spondyloarthropathy Overview of Seronegative Spondyloarthropathies Seronegative spondyloarthropathies (seronegative spondyloarthritides) share certain clinical characteristics (eg, inflammatory back pain, uveitis, gastrointestinal symptoms, rashes). Some are... read more that often seems precipitated by an infection, usually genitourinary or gastrointestinal. Common manifestations include asymmetric arthritis of variable severity that tends to affect the lower extremities with sausage-shaped deformities of fingers or toes or both, large knee effusions, constitutional symptoms, enthesitis, tendinitis, and mucocutaneous ulcers, including hyperkeratotic or crusted vesicular lesions (keratoderma blennorrhagicum). Diagnosis is clinical. Treatment involves nonsteroidal anti-inflammatory drugs 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.

Etiology 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, Clostridioides difficile, Yersinia, or Campylobacter.

Bacille Calmette-Guerin injection for bladder cancer has also been reported to trigger reactive arthritis.

In approximately in 40% of cases, infectious pathogens cannot be identified.

Reactive arthritis is postinfectious arthritis. Although there is evidence of microbial antigens in the synovium, organisms cannot be cultured from joint fluid.

Epidemiology of Reactive Arthritis

The prevalence of the human leukocyte antigen B27 (HLA-B27) allele in patients is 63 to 96% versus 6 to 15% in healthy White controls, thus supporting a genetic predisposition.

Compared to patients without HLA-B27 allele, patients with HLA-B27 allele have more severe arthritis, extraarticular manifestations, and more prolonged courses.

Symptoms and Signs of Reactive Arthritis

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 toes and large joints of the lower extremities and may include large knee effusions. Back pain may occur, usually with severe disease. Joint damage occurs rarely. Axial involvement is more often reported in patients with positive HLA-B27 and usually is asymmetric with large and bulky syndesmophytes.

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 Psoriasis Psoriasis is an inflammatory disease that manifests most commonly as well-circumscribed, erythematous papules and plaques covered with silvery scales. Multiple factors contribute, including... read more Psoriasis ) of the palms and soles and around the nails that become hyperkeratotic and form crusts (keratoderma blennorrhagicum). Keratoderma blennorrhagicum can also include erythema, plaques, and scaling. Nails may become dystrophic. Erythema nodosum Erythema Nodosum Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. It often occurs with... read more Erythema Nodosum has also been reported in reactive arthritis, especially after Yersinia infection.

Mucocutaneous and Skin Manifestations of Reactive Arthritis

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.

Rarely, cardiovascular complications (eg, aortitis, aortic insufficiency, cardiac conduction defects), pleuritis, and central nervous system or peripheral nervous system symptoms develop.

Diagnosis of Reactive Arthritis

  • Typical arthritis

  • Symptoms of antecedent gastrointestinal or genitourinary 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 genitourinary or gastrointestinal 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 Gonorrhea Gonorrhea is caused by the bacterium Neisseria gonorrhoeae. It typically infects epithelia of the urethra, cervix, rectum, pharynx, or conjunctivae, causing irritation or pain and purulent... read more Gonorrhea can closely simulate reactive arthritis. 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, although suggestive, does not. If differentiation is still difficult, a response to ceftriaxone treatment after about a week may be required for simultaneous diagnosis and treatment.

Psoriatic arthritis Psoriatic Arthritis Psoriatic arthritis is a seronegative spondyloarthropathy and chronic inflammatory arthritis that occurs in people with psoriasis of the skin or nails. The arthritis is often asymmetric, and... read more Psoriatic Arthritis can simulate reactive arthritis, causing similar skin lesions, uveitis Overview of Uveitis Uveitis is defined as inflammation of the uveal tract—the iris, ciliary body, and choroid. However, the retina and fluid within the anterior chamber and vitreous are often involved as well.... read more Overview of 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, and tends not to cause mouth ulcers or symptoms of genitourinary or gastrointestinal infection.

Prognosis for Reactive Arthritis

Reactive arthritis often resolves in 3 to 4 months, but up to 50% of patients experience recurrent or prolonged symptoms over several years, especially if induced by chlamydial infection and in patients with positive HLA-B27 alleles. Joint, spinal, or sacroiliac inflammation or deformity may occur with chronic or recurrent disease. Some patients become disabled.

Treatment of Reactive Arthritis

  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

  • Sometimes sulfasalazine, doxycycline, methotrexate, or a combination

  • Supportive measures

NSAIDs (eg, indomethacin 25 to 50 mg orally 3 times a day) usually help relieve symptoms of reactive arthritis. If induced by infection with C. trachomatis, doxycycline 100 mg orally 2 times a day for up to 3 months may accelerate recovery, but this is controversial. Sulfasalazine Traditional disease-modifying antirheumatic drugs (DMARDs) Traditional disease-modifying antirheumatic drugs (DMARDs) as used to treat rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more Rheumatoid Arthritis (RA) may also be helpful. If symptoms are severe despite NSAIDs and sulfasalazine, methotrexate may be considered.

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 Overview of Uveitis Uveitis is defined as inflammation of the uveal tract—the iris, ciliary body, and choroid. However, the retina and fluid within the anterior chamber and vitreous are often involved as well.... read more Overview of 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 a form of spondyloarthropathy that is triggered by infection and 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 nonpurulent genital discharge (eg, urethritis, cervicitis).

  • Confirm the diagnosis with typical arthritic findings plus either symptoms or history of recent genitourinary or gastrointestinal infection or a characteristic extra-articular finding.

  • Treat with nonsteroidal anti-inflammatory drugs (NSAIDs) and sometimes sulfasalazine.

Drugs Mentioned In This Article

Drug Name Select Trade
Azulfidine, Azulfidine En-Tabs, Sulfazine , Sulfazine EC
Ceftrisol Plus, Rocephin
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs
Jylamvo, Otrexup, Rasuvo, RediTrex, Rheumatrex, Trexall, Xatmep
Indocin, Indocin SR, TIVORBEX
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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