Alternate Etiologies Associated Pathogens

This is a form of reactive arthritis (joint inflammation that occurs in response to distant infections or events) characterized by the clinical triad of nongonococcal urethritis, conjunctivitis, and arthritis. This disorder is classified under the group of diseases known as the seronegative spondylarthropathies, which includes: ankylosing spondylitis, psoriatic arthritis, enteropathic arthritis, and Reiters syndrome. The exact pathogenesis remains unknown; however, many infectious agents (particularly Chlamydia trachomatis) and the histocompatibility antigen HLA-B27 have a strong association with this disorder. Symptoms are usually preceded by either urethritis or a diarrheal illness. Reiters syndrome is more common during the third decade of life but does occur in children and the elderly. There is a definite male predominance with the postvenereal form of this syndrome. There is a worldwide distribution of this disorder; however, persons of African heritage are affected less commonly.

Many infectious agents are associated with Reiters syndrome. As stated above, Chlamydia trachomatis and  Ureaplasma urealyticum are common inciting agents. Associated enteric pathogens include Shigella flexneri, Salmonella, Yersinia, and others. Although it was once believed that there was an association between Reiters syndrome and HIV infection, recent studies have shown this not to be true. In fact, Reiters syndrome has been shown to occur in less than 1% of HIV-positive patients. Although the above agents are known to be associated with Reiters syndrome, the exact mechanism of how this disorder results is unknown. It is not known if the disease occurs because the pathogens are actually present in the synovium of affected joints or whether they possess an arthrogenic factor.

Fewer than one-third of affected patients manifest the entire classic triad (urethritis, conjunctivitis, and arthritis). Usually, only two features are present making the diagnosis more difficult. Constitutional symptoms such as fever are usually mild if present. Asymmetric lower extremity arthritis should be enough for the diagnosis to be considered but especially when there is enthesitis, dactylitis, onycholysis of the nails, aphthous ulcers, and associated skin conditions (circinate balanitis or keratoderma blennorrhagicum).

Urethritis, characterized by transient discharge or dysuria, is an early manifestation and occurs 2 to 4 weeks after exposure. Physical exam reveals meatal erythema and edema along with a clear mucoid discharge. In male patients, 80% will manifest prostatitis. Women often suffer silent cystitis or cervicitis without urethritis; however, salpingitis and vulvovaginitis may also occur.

Another early symptom is conjunctivitis. This is usually a mild and transient symptom that may be either unilateral or bilateral and noninfectious. Uveitis may also occur, and when it does, it is acute and unilateral.

Arthritic symptoms develop within 1 to 3 weeks of the initial infection. The arthritis is polyarticular and asymmetric, involving the knees, ankles, feet, and wrists most commonly. Enthesopathy (inflammation of periarticular structures and bone-tendon insertions) is common. Sausage digits refers to dactylitis, or the involvement of the fingers or toes with local enthesopathy. This gives the digits a uniformly swollen appearance. The presence of sausage digits is significant in that it limits the differential diagnosis to only two disorders, Reiters syndrome or psoriatic arthritis. Other common arthritic manifestations include sacroiliitis and an enthesopathic process of the ankle affecting the Achilles tendon and plantar fascia.

Dermatologic manifestations are numerous and include balanitis circinata, keratoderma blenorrhagica, and oral ulcers. Balanitis circinata refers to painless ulcers of the glans penis and urethral meatus. Keratoderma blenorrhagica is a condition that affects the soles of the feet but may also include the scrotum, palms, penis, trunk, and scalp. Initially, it begins as clear vesicles situated on an erythematous base that progress to macules, papules, and eventually to small keratotic nodules. Oral ulceration occurs early in the disease course and begins as vesicles. The oral lesions are superficial and painless.

Laboratory abnormalities are nonspecific but generally include a mild normocytic anemia, leukocytosis, and thrombocytosis along with an elevated ESR or CRP. Evaluation for the presence of antinuclear antibodies (ANA) and rheumatoid factor (RF) are negative. Since culture techniques for Chlamydia trachomatis are inefficient, urethral swabs and cervical cytobrushings should be submitted for either direct fluorescent antibody and enzyme-immunoassay tests. Newer studies include PCR techniques for the detection of C. trachomatis. Stool cultures should be obtained to determine the presence of associated enteric pathogens even when gastrointestinal symptoms are mild. Approximately 80% of cases are associated with the presence of positive HLA-B27 although this test is too nonspecific to be of help in most cases.

Radiographically, asymmetric sacroiliitis occurs in 10% of patients early in the disease course but increases to 70% of patients with chronic Reiters syndrome. The lower three thoracic or upper three lumbar vertebrae may display asymmetric paravertebral comma-shaped ossification and enthesitis may be associated with an underlying periosteal reaction.

Treatment is usually directed at symptomatic relief. NSAIDs are effective symptomatic therapy. Research has shown that anti-chlamydial therapy for 3 months may help speed recovery in patients with Reiters syndrome secondary to Chlamydia trachomatis. Therapy for these patients should entail doxycycline tablets 100 mg PO BID for 3 months.

The clinical course of this disorder is variable. Most patients are asymptomatic 3 months to 1 year after symptoms first appear; however, many patients may suffer from recurrent arthritic symptoms.