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Dr. Maria Michailidou



Reactive Arthritis

Essentials of Diagnosis

Asymmetric, oligoarticular inflammatory arthritis of the lower extremities. Enthesitis and dactylitis. Axial skeleton involvement characterized by unilateral sacroiliitis. Associations with antecedent genitourinary and gastrointestinal infections. Extra-articular manifestations, including conjunctivitis, anterior uveitis, urethritis, oral ulcers, circinate balanitis, and keratoderma blennorrhagicum.

General Considerations

The typical patient is a male in his 20s, but reactive arthritis also occurs in women and can affect  individuals over a wide age span. Peripheral arthritis, usually in the form of an oligoarthritis of the lower extremities and acute in onset, characterizes reactive arthritis. Enthesitis and dactylitis are often prominent, and approximately 50% of patients have mucocutaneous manifestations. Reiter syndrome refers to the triad of reactive arthritis, conjunctivitis, and urethritis, but this term has fallen out of favor, particularly following recent revelations of Reiter's involvement in war crimes during World War II.

Genitourinary infections with Chlamydia trachomatis or gastrointestinal infections with Shigella, Salmonella, Yersinia, or Campylobacter species can trigger reactive arthritis, generally after a lag of 1–4 weeks. Cultures of synovial fluid and synovium, however, are sterile (hence the term "reactive"). Often, however, there is no history of antecedent infection, suggesting that reactive arthritis can follow subclinical infections or that there are other environmental triggers. The prevalence and severity of reactive arthritis may be increased in persons infected with HIV (see

The majority of cases of reactive arthritis spontaneously resolve over months, but a substantial minority will have either a relapsing course or persistent arthritis.

 Clinical Findings

Symptoms and Signs

The onset of the joint disease is usually acute with the appearance of an additive, asymmetric oligoarthritis most commonly affecting the knees and ankles. Involvement of upper extremity joints occurs but is uncommon. Urethritis and mild conjunctivitis may precede articular symptoms. In contrast to rheumatoid arthritis, fever > 38 °C is not uncommon at the outset of reactive arthritis, and weight loss can be striking.

Heel pain, due either to Achilles tendinitis or enthesitis where the plantar fascia inserts onto the inferior aspect of the calcaneus, is common. Dactylitis, usually in the form of "sausage toes," occurs in approximately half of cases.

Approximately 50% of patients have low back pain, but radiographic evidence of involvement of the axial skeleton occurs in only 20%. Sacroiliitis and spondylitis, however, become more prevalent with disease duration, and up to 70% with persistent disease have disease of the axial skeleton. Sacroiliitis is usually unilateral but may become bilateral with time. In a small minority of cases, spondylitis leads to extensive fusion of the spine as can be seen in ankylosing spondylitis.

Mucocutaneous disease is common and can provide important clues to the diagnosis. Although urogenital infections with C trachomatis can induce reactive arthritis, urethritis and cervicitis also can be manifestations of the mucosal inflammation that is part of the disease process and can occur with the postenteric forms of reactive arthritis, particularly early in the disease course. Other early mucocutaneous manifestations include shallow, painless ulcers of the palate, tongue, and the glans penis (circinate balanitis). Approximately 25% of patients with reactive arthritis have keratoderma blennorrhagicum, a papulosquamous rash of the soles and palms ( that clinically and histologically resembles pustular psoriasis. Subungual deposits of keratotic material can produce nail changes similar to those of psoriasis.  

Up to one-third of cases have conjunctivitis that is usually mild and present early in the disease course. Conjunctivitis is not associated with HLA-B27 and is the least specific extra-articular manifestation of reactive arthritis. Anterior uveitis and aortitis also occur although the prevalence of these in reactive arthritis is less than in ankylosing spondylitis .

Laboratory Findings

Patients with active disease often have mild anemia, modest leukocytosis, and moderate to marked thrombocytosis. The erythrocyte sedimentation rate and levels of C-reactive protein are usually elevated. Tests for rheumatoid factor and antinuclear antibodies are negative.

Synovial fluid is inflammatory with white blood cell counts usually ranging from 5000 to 50,000/L. Synovial fluid cultures are negative. Patients with genitourinary symptoms should be tested for infection with C trachomatis.

Testing for HLA-B27 can aid diagnosis in selected cases. The association with HLA-B27 is strongest in the subset of patients with persistent disease and involvement of the axial skeleton.

Imaging Studies

Enthesopathy at the insertion of the plantar fascia produces periostitis and "inflammatory heel spurs." These can be differentiated from degenerative spurs of the calcaneus by the degree of cortication, as the inflammatory lesions tend to be fluffy in appearance, in contrast to well-corticated degenerative spurs. Patients with disease of the axial skeleton have sacroiliitis that is usually unilateral and spondylitis characterized by nonmarginal syndesmophytes ().

Differential Diagnosis

The diagnosis of reactive arthritis is based on the clinical presentation and the exclusion of alternative explanations for an inflammatory oligoarthritis.

In the early stages it is critical to exclude infectious causes of arthritis. Disseminated gonococcal infection (DGI) can be particularly difficult to distinguish from acute-onset reactive arthritis because oligoarthritis, tenosynovitis, and fever occur in both diseases. Urethral, pharyngeal, cervical, and rectal swabs for gonococci have, in combination, a sensitivity of 70–90% in DGI. Synovial fluid cultures, in contrast, are positive in < 50% of cases of DGI, and therefore, sterile synovial fluid cultures do not distinguish reactive arthritis from DGI. Occasionally, a therapeutic trial of antibiotics is necessary to make this diagnostic distinction; a prompt response to appropriate antibiotic therapy points to a diagnosis of DGI.

Nongonococcal septic arthritis can be oligoarticular and occasionally mimics reactive arthritis; synovial fluid cultures are usually positive, underscoring the importance of diagnostic arthrocentesis in cases of unexplained acute oligoarthritis. Bacterial endocarditis can produce an oligoarthritis due to either direct infection (with positive synovial fluid cultures) or immune complexes (with sterile synovial cultures); back pain is common, especially with acute endocarditis. Acute viral infections, such as parvovirus B19, usually cause an acute polyarthritis, but occasionally the arthritis involves only a few joints. An antecedent sore throat suggests post-streptococcal arthritis which, in adults, usually is additive and is not associated with the extra-articular manifestations of acute rheumatic fever.

Occasionally, rheumatoid arthritis begins as an oligoarthritis and causes some diagnostic confusion with reactive arthritis. Inflammatory low back pain and dactylitis are not features of rheumatoid arthritis, and their presence should point to reactive arthritis or another spondyloarthropathy. Dactylitis can a helpful clue to the presence of a spondyloarthropathy (particularly reactive arthritis or psoriatic arthritis) but also can be seen in gout and sarcoidosis.


The treatment of reactive arthritis mirrors the therapeutic approach to ankylosing spondylitis discussed earlier. NSAIDs are widely used. Sulfasalazine appears to be efficacious for peripheral arthritis but of little or no efficacy for disease of the axial skeleton. Methotrexate has been widely used and is likely beneficial, although its efficacy in this disease has not been established in rigorously performed clinical trials. The anti-TNF therapies, infliximab and etanercept, produce prompt and substantial responses. These are currently the treatment of choice for severe disease.

The use of antibiotics in the treatment of reactive arthritis is still somewhat contentious. Genitourinary infections with Chlamydia should be treated. Prolonged (months) treatment with tetracyclines has been reported to be beneficial for patients with post-chlamydial reactive arthritis, but there is not general agreement on this issue. Antibiotics do not appear to be effective in the treatment of postenteric and idiopathic forms of reactive arthritis.


Disability due to destructive peripheral arthritis or extensive disease of the spine develops in a minority of patients. Amyloidosis and aortic regurgitation are rare complications of long-standing disease.