Reactive Arthritis
Reactive arthritis is classified as a member of the spondyloarthritis family, and shares features with undifferentiated spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, and spondyloarthritis associated with inflammatory bowel disease. The term reactive arthritis was introduced in 1969 as "an arthritis which developed soon after or during an infection elsewhere in the body, but in which the microorganisms or the viruses cannot be recovered from the joint" In the most restricted sense, reactive arthritis has been used to refer to the triad of post-infectious arthritis, urethritis, and conjunctivitis, formerly called Reiter syndrome.
Multiple alternative terms, diagnostic, and classification approaches and criteria have been proposed. None of the alternative terms, criteria, or diagnostic approaches has been validated by prospective studies, nor are any universally accepted by the scientific community. Many of the studies generating these diagnostic approaches involve patients seen in rheumatology clinics, but the patient populations seen by rheumatologists may be very different from those seen in the general community. Thus, strictly speaking, reactive arthritis is still an evolving concept rather than an entity with validated diagnostic, or even classification, criteria.
Reactive arthritis is an uncommon disease that typically occurs in young adults, affecting both men and women. Much of the data on the prevalence and annual incidence of reactive arthritis in populations come from the Scandinavian countries. The prevalence is estimated to be 30 to 40 per 100,000 adults, and the annual incidence from 5 to 28 per 100,000. Most cases of reactive arthritis appear sporadically, but outbreaks may follow single source infections. In such outbreaks, the percent of infected subjects who developed subsequent reactive arthritis varies from 0 to 21 percent. The causative pathogens, the incidence and the prevalence of reactive arthritis depend upon the localities.
Two types of bacteria can cause reactive arthritis: those causing enteric infections and those causing urethritis. The enteric bacteria associated with reactive arthritis include: Salmonella, Shigella, especially Shigella flexneri, but also Shigella dysenteriae and sonnei, Yersinia including Yersinia enterocolitica and pseudotuberculosis, Campylobacter especially Campylobacter jejuni and Clostridium difficile. Viral infections like EBV, CMV, Parvovirus B19, Hepatitis or Herpetic viruses may also induce a reactive viral arthropathy.
The only genital pathogen commonly accepted to be the cause of reactive arthritis is Chlamydia trachomatis. The classical symptoms of these infections are diarrhea or urethritis. Patients with arthritis induced by enteric bacteria can also develop aseptic urethritis. It is also possible for the causative infection to be asymptomatic. A number of other bacteria have been reported to cause reactive arthritis, including Mycoplasma genitalium, Ureaplasma urealyticum and Chlamydia pneumoniae, beta-hemolytic Streptococci, Neisseria gonorrhea, and vaccination with some live vaccines. These organisms can induce arthritis, but they are not regarded as a spondyloarthritis or reactive arthritis. Reactive arthritis has been reported in patients with HIV infection. In HIV-infected Caucasians, but not Africans, an association between reactive arthritis and HLA-B27 has been noted.
Musculoskeletal signs and symptoms
The musculoskeletal features of reactive arthritis include two features: arthritis and enthesitis.
- Arthritis
- Typical picture of arthritis, seen in rheumatology clinics, is an asymmetric oligoarthritis, often affecting the lower extremities. However, about 50 percent of patients have arthritis in the upper extremities, and some have polyarthritis in the small joints.
- Enthesitis
- Classical symptoms and signs of enthesitis are swelling at the heels, and sausage digits. Common sites of involvement are at the insertions of the Achilles tendon and of the plantar fascia on the calcaneus. Pain, swelling, and local tenderness are suggestive clinical features. Extra-articular involvement in reactive arthritis is associated with a variety of manifestations. These include: Genitourinary tract symptoms, such as dysuria and pelvic pain, conjunctivitis and, less frequently, anterior uveitis, oral ulcers, rashes such as keratoderma blennorrhagica (hyperkeratotic skin lesions on soles and palms), nail changes that resemble those seen in psoriasis and genital lesions such as circinate balanitis.
Dysuria or pelvic pain may be a manifestion of sterile urethritis (aseptic urethritis or culture negative urthritis) that may be a prominent and troublesome clinical feature. The optimal treatment for urethral symptoms following appropriate treatment for gonococcal or chlamydial genitourinary infection, or following enteric infection is uncertain. There have been no clinical trials to guide therapeutic decisions.
- Classical symptoms and signs of enthesitis are swelling at the heels, and sausage digits. Common sites of involvement are at the insertions of the Achilles tendon and of the plantar fascia on the calcaneus. Pain, swelling, and local tenderness are suggestive clinical features. Extra-articular involvement in reactive arthritis is associated with a variety of manifestations. These include: Genitourinary tract symptoms, such as dysuria and pelvic pain, conjunctivitis and, less frequently, anterior uveitis, oral ulcers, rashes such as keratoderma blennorrhagica (hyperkeratotic skin lesions on soles and palms), nail changes that resemble those seen in psoriasis and genital lesions such as circinate balanitis.
Treatment
Non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of symptomatic therapy during the acute stage of inflammation. Joint injections with steroids are also beneficial. Antibiotics are not used to treat the arthritis specifically, though they may be indicated if there is evidence of ongoing intestinal or genitourinary infection. When response to NSAIDs and local injections is unsatisfactory, use of a DMARD is indicated. Sulfasalazine is significantly more effective than placebo. Anti-TNF agents — A chimeric anti-tumor necrosis factor (TNF) alpha monoclonal antibody (infliximab) a human monoclonal antibody (adalimumab), and the soluble TNF alpha receptor-immunoglobulin fusion protein (etanercept) have all received regulatory approval for use in treating ankylosing spondylitis. For patients with reactive arthritis that is refractory to NSAIDs and intraarticular glucocorticoid injections, and who do not respond to or have a contraindication to the use of sulfasalazine, we suggest a trial of an anti-TNF agent, such as etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously twice a month. Limited use of prednisone at low dose of 10 mg/day for two to three weeks may be also beneficial.