Reactive arthritis

Reiter's syndrome
Classification and external resources
Reactive arthritis of the knee following Gonorrhea infection
ICD-10	M02
ICD-9	099.3
DiseasesDB	29524
MedlinePlus	000440
eMedicine	med/1998
MeSH	C01.539.100.500

Reactive arthritis is classified as an autoimmune condition that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease.^[1] By the time the patient presents with symptoms, often the "trigger" infection has been cured or is in remission in chronic cases, thus making determination of the initial cause difficult.

The clinical pattern of reactive arthritis commonly consists of an inflammation of fewer than five joints which often includes the knee or sacroiliac joint. The arthritis may be "additive" (more joints become inflamed in addition to the primarily affected one) or "migratory" (new joints become inflamed after the initially inflamed site has already improved).^[2][3]

The arthritis often is coupled with other characteristic symptoms; this is called Reiter's syndrome or Reiter's arthritis. The manifestations of Reiter's Syndrome include the following triad of symptoms: an inflammatory arthritis of large joints, inflammation of the eyes in the form of conjunctivitis or uveitis, and urethritis in men or cervicitis in women. Patients can also present with mucocutaneous lesions, as well as psoriasis-like skin lesions such as circinate balanitis, and keratoderma blennorrhagicum. Enthesitis can involve the Achilles tendon resulting in heel pain.^[4] Not all affected persons have all the manifestations.

Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis^[5] often precipitated by genitourinary or gastrointestinal infections. The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis or Neisseria gonorrheae).

It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population.^[6][7] Patients with HIV have an increased risk of developing Reactive arthritis as well.

A large number of cases during World Wars I and II focused attention on the triad of arthritis, urethritis, and conjunctivitis (often with additional mucocutaneous lesions) which at that time was also referred to as "Fiessenger-Leroy-Reiter syndrome". These eponyms are now of historic interest only.^[8]

Signs and symptoms

Keratoderma blennorrhagicum due to Reactive arthritis

Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic for Reiter's syndrome is "Can't see, can't pee, can't climb a tree."^[9]

Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease. The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination. Other urogenital problems may arise such as prostatitis in men and cervicitis, salpingitis and/or vulvovaginitis in women.

The arthritis that follows usually affects the large joints such as the knees causing pain and swelling with relative sparing of small joints such as the wrist and hand.

Eye involvement occurs in about 50% of men with urogenital reactive arthritis syndrome and about 75% of men with enteric reactive arthritis syndrome. Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision. Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go.

Roughly 20 to 40 percent of the men with the disease develop penile lesions called balanitis circinata (circinate balanitis). A small percentage of men and women develop small hard nodules called keratoderma blennorrhagicum on the soles of the feet and, less commonly, on the palms of the hands or elsewhere. In addition, some individuals with reactive arthritis develop mouth ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. Some patients suffer serious gastrointestinal problems similar to those of the Crohn's disease.

About 10 percent of the people with reactive arthritis, especially those with a prolonged course of the disease, will develop cardiac manifestations, including aortic regurgitation and pericarditis. Reiter's Syndrome has been described as a pre-cursor for other joint conditions, including ankylosing spondylitis.

In the oral cavity, the patients may suffer from recurrent aphthous stomatitis, geographic tongue and migratory stomatitis in higher prevalence than the general population.^[10]

Causes

Reactive arthritis is associated with the HLA-B27 gene on chromosome 6 and by the presence of enthesitis as the basic pathologic lesion^[11] and is triggered by a preceding infection. The most common triggering infection in the US is a genital infection with Chlamydia trachomatis and other bacteria known to cause reactive arthritis which are more common worldwide are Ureaplasma urealyticum, Salmonella spp., Shigella spp., Yersinia spp., and Campylobacter spp.^[12] A bout of food poisoning or a gastrointestinal infection may also precede the disease (those last four genera of bacteria mentioned are enteric bacteria). There is some circumstantial evidence for other organisms causing the disease, but the details are unclear.^[13] Reactive arthritis usually manifests about 1–3 weeks after a known infection. The mechanism of interaction between the infecting organism and the host is unknown. Synovial fluid cultures are negative, suggesting that reactive arthritis is caused either by an over-stimulated autoimmune response or by bacterial antigens which have somehow become deposited in the joints.

Diagnosis

There are few clinical symptoms, but the clinical picture is dominated by arthritis in one or more joints, resulting in pain, swelling, redness, and heat sensation in the affected areas.

The urethra, cervix and the throat may be swabbed in an attempt to culture the causative organisms. Cultures may also be carried out on urine and stool samples or on fluid attained by arthrocentesis.

Tests for C-reactive protein and erythrocyte sedimentation rate are non-specific tests that can be done to corroborate the diagnosis of the syndrome. Also, a blood test for the genetic marker HLA-B27 may be performed. About 75 percent of all the patients with Reiter's arthritis display this gene.

Diagnostic Criteria

Although there are no definitive criteria to diagnose the existence of reactive arthritis, the American College of Rheumatology has published sensitivity and specificity guidelines.^[14]

Treatment

The main goal of treatment is to identify and eradicate the underlying infectious source with the appropriate antibiotics if still present. Otherwise, treatment is symptomatic for each problem. Analgesics particularly NSAIDs, sulfasalazine, steroids and immunosuppressants may be needed for patients with severe reactive symptoms that do not respond to any other treatment.

Prognosis

Reactive arthritis may be self-limiting, frequently recurring, chronic or progressive. Most patients have severe symptoms lasting a few weeks to six months. 15 to 50 percent of cases have recurrent bouts of arthritis. Chronic arthritis or sacroiliitis occurs in 15-30 percent of cases. Repeated attacks over many years are common, and patients sometimes end up with chronic and disabling arthritis, heart disease, amyloid deposits, ankylosing spondylitis, immunoglobulin A nephropathy, cardiac conduction abnormalities, or aortitis with aortic regurgitation.^[15] However, most people with reactive arthritis can expect to live normal life spans and maintain a near-normal lifestyle with modest adaptations to protect the involved organs.

Epidemiology

Because women may be underdiagnosed, the exact incidence of reactive arthritis is difficult to estimate. A few studies have been completed, though. In Norway between 1988 and 1990, incidence was 4.6 cases per 100,000 for Chlamydia-induced Reiter's Syndrome and 5 cases per 100,000 for that induced by enteric bacteria.^[16] In 1978 in Finland, the annual incidence was found to be 43.6 per 100,000.^[17]

History

When reactive arthritis appears in a triad that also includes ophthalmic and urogenital manifestations, the eponym "Reiter's syndrome" is often applied; German physician Hans Conrad Julius Reiter described the condition in a soldier he treated during World War I.

A number of physicians have suggested that the eponym is undeserved. Dr. Reiter's Nazi Party affiliation, and in particular his involvement in forced human experimentation in the Buchenwald concentration camp (which, after his capture at the end of World War II, resulted in his prosecution in Nuremberg as a war criminal), have come to overshadow his medical accomplishments. Furthermore, he was not the first physician to make associations between the arthritis and other symptoms—the names arthritis urethritica, venereal arthritis and polyarteritis enterica had previously been applied—and the full triad was described by another physician in the 19th century.^[18]

Notable cases

• It has been postulated that Italian-born explorer Christopher Columbus had Reiter's arthritis, dying from a heart attack caused by the condition.^[19]
• Scottish football player Ian Murray had Reiter's arthritis.^[20]

References

External links

• eMedicine
• Reactive arthritis topic list - Merck Manual
• Reiter's Syndrome - WrongDiagnosis.com
• MorbusReiter.de one patient of the rare reactive arthritis is offering to other patients a platform with information, guestbook and forum.