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Reactive Arthritis, Musculoskeletal
Updated: Feb 21, 2007
Introduction
Background
Reiter syndrome was originally defined as a triad of arthritis, conjunctivitis, and urethritis. Hans Reiter first reported this triad of symptoms in 1916, and Bauer and Engelman formally described it as a syndrome in 1942.
A term frequently associated with Reiter syndrome is reactive arthritis. Ahvonen and coworkers introduced this term in 1969. Reactive arthritis is used to describe an acute arthritis complicating an infection elsewhere in the body in which the infecting organism cannot be cultured from the joint fluid or synovium.
Approximately 80% of patients are positive for the histocompatability antigen called human leukocyte antigen (HLA)-B27; therefore, reactive arthritis is strongly associated with HLA-B27. Reiter syndrome is now thought to be only 1 clinical manifestation of reactive arthritis. Because of its association with HLA-B27 and its clinical overlap with ankylosing spondylitis and psoriatic arthritis, reactive arthritis and Reiter syndrome are classified as types of seronegative (for rheumatoid factor) spondyloarthropathy.
Pathophysiology
Two factors are important in the pathogenesis of Reiter syndrome. First, in some patients, the arthritis is clearly induced by infection. Second, most patients share HLA-B27 typing.
Infection
Bacteria that have been identified as definite triggers include Shigella, Salmonella, and Yersinia species, Campylobacter jejuni; and Chlamydia trachomatis. Other pathogens are those related to lymphogranuloma venereum. Most of these organisms are thought to produce lipopolysaccharide, and they share a capacity to attack mucosal surfaces, to invade host cells, and to survive intracellularly.
Antigens from these organisms have been detected in the synovium or in synovial-fluid leukocytes in patients with reactive arthritis and/or Reiter syndrome for long periods after acute episodes. Antigen-specific T cells likely play an important role, though the precise mechanism remains to be determined.
Reiter disease is not uncommon after HIV infection. The spectrum of inflammatory and reactive arthropathies includes Reiter syndrome, psoriatic arthritis, and HIV-associated arthritis. Patients with atypical musculoskeletal complaints and a suspected history of exposure should be tested for HIV.
Reiter syndrome has also been reported as an uncommon complication after intravesical bacillus Calmette-Guérin (BCG) immunotherapy for bladder carcinoma.
HLA-B27
As with bacterial antigens, the role of HLA-B27 also remains to be determined. In vitro findings indicate that the presence of HLA-B27 significantly prolongs the intracellular survival of Yersinia enterocolitica and Salmonella enteritides in human and murine cell lines. One hypothesis suggests that prolonged intracellular bacterial survival promoted by HLA-B27 and other factors permit infected leucocytes to travel from the site of primary infection to the joints, where a T-cell response to persistent bacterial antigens promotes arthritis.
Frequency
United States
About 1-2% of patients with nonspecific urethritis who are examined at clinics for sexually transmitted diseases have reactive arthritis, and the rates after outbreaks of shigellosis are similar. A man with HLA-B27 has a 20% risk of developing reactive arthritis after an episode of Shigella -related dysentery.
The overall incidence and prevalence is difficult to assess because of the variable prevalence of the triggering infections and of the genetic susceptibility in different populations. For example, in Minnesota, the incidence has been estimated to be 3.5 cases per 100,000 population per year. In contrast, in a population with a high rate of genitourinary and gastrointestinal infections (eg, urban homosexual and bisexual men), the prevalence may approach 1 case per 1000 population.
International
See In the US above.
Mortality/Morbidity
- The arthritic episodes are short and self-limiting.
- Recurrences are frequent, and residual disability and deformity occurs in 5% of patients.
- Chronic changes are most common in the metatarsophalangeal joints, heel, lumbar spine, knee, and ankle.
Race
The prevalence of Reiter syndrome is higher in white people than in black people.
Sex
- Although Reiter syndrome is predominantly a disease of young men, the apparent male-to-female ratio of 50:1 is spuriously high.
- With the recognition that the initiating infectious episode might be silent cystitis or cervicitis, the male-to-female ratio is more likely to be 5:1.
- Postdysentery reactive arthritis has an equal sex distribution.
Age
The disease is most common in individuals aged 18-40 years, but it can occur in children as young as 5 years of age and in older adults.
Presentation
The clinical features of Reiter syndrome range from transient monoarthritis to severe multisystemic disease. In most cases, careful history taking elicits evidence of an antecedent infection 1-4 weeks before the onset of the symptoms of reactive disease. Buccal ulceration, balanitis, and sacroiliitis can also occur. The disease is often not self-limiting and may progress, with 80% of patients having symptoms at 5 years.
In about 50% of patients with Reiter disease, urethritis, conjunctivitis, and an inflammatory oligoarthritis simultaneously develops 1-3 weeks after sexual exposure or an episode of dysentery. The urethritis in Reiter disease is usually associated with mild dysuria, but occasional cases involve severe dysuria and hematuria resulting from acute hemorrhagic cystitis and prostatitis.
Constitutional symptoms are common. These include fatigue, malaise, fever, and weight loss. Musculoskeletal symptoms are usually acute in onset, and low backache is common.
Arthritis is asymmetric and additive, with involvement of new joints occurring over a few days to a few weeks. The joints of the lower extremities—especially the knee; ankle; and subtalar, metatarsophalangeal, and interphalangeal joints—are the most common sites of involvement. The arthritis is usually painful, and joint effusions are common in the knee. Dactylitis, or sausage digits, is another feature. Tendinitis with retrocalcaneal bursitis and plantar fasciitis are characteristic lesions.
Although Reiter disease is a common cause of plantar fasciitis, this finding is not pathognomonic. Plantar fasciitis can also be seen in other rheumatologic conditions such as ankylosing spondylitis, rheumatoid arthritis, and gout.
Urethritis may be a principal feature. As a precipitating event, it precedes the symptom of reactive arthritis by 1-3 weeks. Men experience frequency and dysuria. Examination of the penis shows meatal erythema and edema. Prostatitis is common and has been reported in up to 80% of patients.
Hemorrhagic cystitis may develop and resolve spontaneously. Similarly, females can have vulvitis, cervicitis, or salpingitis.
Ocular disease is common, ranging from transient asymptomatic conjunctivitis to an aggressive anterior uveitis that is occasionally refractory to treatment and causes blindness.
Mucocutaneous lesions are common. Oral ulcers are superficial, transient, and often asymptomatic. The characteristic skin lesion, keratoderma blennorrhagica, consists of vesicles that become hyperkeratotic and that ultimately form a crust before disappearing. They are most common on palms and soles. Lesions on glans penis, termed circinate balanitis, are common and consist of vesicles that rupture to form painless superficial erosions.
Nail changes are common and consist of onycholysis and distal yellowish discoloration.
Less frequent features include cardiac conduction defects, aortic insufficiency, lesions of the central nervous system and peripheral nervous system, and pleuropulmonary infiltrates.
Preferred Examination
Imaging study
Radiography is most important imaging technique for the detection of Reiter syndrome.
Laboratory studies
The erythrocyte sedimentation rate and C-reactive protein level are elevated during the acute phase of the disease. A moderate neutrophilic leukocytosis may be present. Chronic cases may show a mild normocytic anemia. Levels of C3 and C4, which are acute-phase reactants, are also increased. Results for antinuclear antibodies and rheumatoid factor are negative.
Synovial fluid has an elevated white blood cell count with a predominance of neutrophils. The fluid may contain large macrophages with vacuoles containing nuclear debris and whole leucocytes. These are called Reiter cells, but they are nonspecific for Reiter syndrome. The presence of HLA-B27 antigen is correlated with axial disease, carditis, and uveitis.
Differential Diagnoses
Ankylosing Spondylitis
Psoriatic Arthritis
Rheumatoid Arthritis, Spine
Other Problems to Be Considered
Enteropathic arthritis
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References
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Further Reading
Keywords
Reiter syndrome, Reiter's syndrome, Reiter disease, Reiter's disease, reactive arthritis, human leukocyte antigen B27, HLA-B27, seronegative spondyloarthropathy
