Introduction
Background
In 1916, Hans Reiter described the classic triad of arthritis, nongonococcal urethritis, and conjunctivitis.1 However, he mistakenly dubbed this disease as "spirochetosis arthritica."2 This condition used to be known as Reiter syndrome but is now referred to as reactive arthritis (ReA).1 This change has occurred in part because of Hans Reiter's affiliation and activities with the Nazis during WWII.
Cases of "Reiter's disease" have likely been described dating back many centuries. In fact, Christopher Columbus may have suffered from its effects having described symptoms such as fever, arthritis, eye hemorrhage, and pain, following a bout of dysentery. His arthritis later progressed to a chronic bedridden state he attributed to "gout."2
Reactive arthritis refers to acute nonpurulent arthritis complicating an infection elsewhere in the body.
Reactive arthritis falls under the rheumatic disease category of seronegative spondyloarthropathies, which includes ankylosing spondylitis, psoriatic arthritis, the arthropathy of associated inflammatory bowel disease, juvenile-onset ankylosing spondylitis, juvenile chronic arthritis, and undifferentiated spondyloarthritis.3
A study by Kaarela et al reported that reactive arthritis and ankylosing spondylitis appear to be identical. They assessed long-term outcome of reactive arthritis and ankylosing spondylitis to identify similarities in manifestations of disease. A number of similarities were found; among them, sacroiliitis, peripheral arthritis, and iritis developed most often in both chronic reactive arthritis and ankylosing spondylitis.4
Pathophysiology
Reactive arthritis is triggered following enteric or urogenital infections. Reactive arthritis is associated with human leukocyte antigen (HLA)–B27, although HLA-B27 is not always present in an affected individual, particularly in the presence of HIV.
Rihl et al found a high proportion of proangiogenic factors accounting for a genetically determined susceptibility to reactive arthritis.5
Bacteria associated with reactive arthritis are generally enteric or venereal and include the following: Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis,6 Streptococcus viridans, Mycoplasma pneumonia, Cyclospora,7 Chlamydia trachomatis, Yersinia enterocolitica, and Yersinia pseudotuberculosis. Bacteria or their components (RNA, DNA) have been identified in synovial fluid cells, synovial biopsy specimens, and circulatory monocytes.
Interestingly, severely symptomatic enteric infections are associated with an increased likelihood of developing reactive arthritis,2,8 whereas, more frequently, asymptomatic venereal infections cause this disease.2
Frequency
United States
Frequency is estimated at 3.5 cases per 100,000. (Because of uncertainty of diagnosis and variations in definitions, epidemiologic features are difficult to calculate.)
An estimated 1-3% of all patients with a nonspecific urethritis develop an episode of arthritis. The incidence is 1-4% following enteric infection. This number jumps to 20-25% following bacterial enteritis in HLA-B27-positive individuals.9 Prevalence of inapparent chlamydial infections, underdiagnosis, and underreporting may make incidence even higher.8
After outbreak of S enteritidis, 29% had reactive arthritis.6
International
In Norway, an annual incidence of chlamydia-induced reactive arthritis of 4.6 cases per 100,000 population and an incidence of enteric bacteria–induced reactive arthritis of 5 cases per 100,000 population were reported in 1988-1990. Inciting infections may be endemic to certain geographic locations. For example, the incidence of Yersinia enterocolitica is higher in Europe than in North America and thus is responsible for cases of reactive arthritis in countries such as Finland and Norway.2
Occurrence appears to be related to the prevalence of HLA-B27 in a population and the rate of urethritis/cervicitis and infectious diarrhea. More than 40 subtypes of HLA-B27 are known. Those associated with the spondyloarthropathies are HLA-B2702, B2704, and B2705.10 These subtypes may be somewhat geographically segregated. For example, the subtype B2705 is predominantly found in Latin America, Brazil, Taiwan, and parts of India. Interestingly, subtypes HLA-B2706 and B2709, found in native Indonesia and Sardinia, respectively, may be partially protective from reactive arthritis.11
Mortality/Morbidity
Most patients have severe symptoms lasting weeks to 6 months. Approximately 15-50% have recurrent bouts of arthritis. Chronic arthritis or sacroiliitis occurs in 15-30% of cases.
Race
Reactive arthritis is reported most frequently in whites. When reactive arthritis occurs in black persons, it is frequently B27-negative.
Occurrence appears to be related to HLA-B27 prevalence in the population.
Sex
The male-to-female postvenereal ratio is traditionally 5-10:1. The postenteric ratio is 1:1.
Age
The peak onset is in persons aged 15-35 years; reactive arthritis is rarely seen in children. Cases in children are almost entirely postenteric.
Clinical
History
- Symptoms of reactive arthritis generally appear within 1-3 weeks but can range from 4-35 days from onset of inciting episode of urethritis/cervicitis or diarrhea. The classic triad of symptoms, found in only one third of patients with reactive arthritis, has a sensitivity of 50.6% and a specificity of 98.9%.12
- Constitutional symptoms (usually mild):
- Fever (usually low grade)
- Malaise
- Musculoskeletal symptoms:
- Myalgias (early)
- Asymmetric arthralgia, joint stiffness, primarily involving the knees, ankles, and feet (wrists may be early target)
- Low back pain (49%) with radiation to the buttocks or thighs12
- Symptoms worse with rest or inactivity
- Urethritis associated with reactive arthritis may be postdysenteric or postvenereal, with frequency, dysuria, urgency, and urethral discharge. It may be mild or inapparent. Urogenital symptoms either the result of UG infection or postdysenteric are found in 90% of patients with reactive arthritis.12
- Ophthalmologic symptoms:
- Erythema
- Burning
- Tearing
- Photophobia
- Pain
- Decreased vision (rare)
- Patients may have mild recurrent abdominal complaints after precipitating episode of diarrhea.
Physical
- A scoring system for diagnostic points in Reiterlike spondyloarthropathies exists. Two or more of the following points establishes diagnosis (one of which must pertain to the musculoskeletal system):
- Asymmetric oligoarthritis, predominantly of the lower extremity
- Sausage-shaped finger (dactylitis), toe or heel pain, or other enthesitis
- Cervicitis or acute diarrhea within 1 month of the arthritis
- Conjunctivitis or iritis
- Genital ulceration or urethritis
- Musculoskeletal findings:
- Asymmetric pauciarticular arthritis affecting mainly the lower extremities with low-grade inflammation may be observed.13
- The knee may become markedly edematous.
- Distinctive arthropathy of reactive arthritis includes local enthesopathy, which is inflammation at the tendinous or ligamentous insertion into bone, rather than synovium (common in insertions into calcaneus, talar, and subtalar joints). Plantar fasciitis is commonly observed.
- Dactylitis or sausage finger or toe is caused by uniform inflammation and found in approximately 17% of patients.12
- Osteitis
- Urogenital symptoms may be primary or postdysenteric:
- Meatal edema and erythema and clear mucoid discharge
- Prostatitis causing tenderness (up to 80%) and vulvovaginitis
- Circinate balanitis, shown in the image below
Circinate balanitis in a patient with reactive arthritis.
- Other urogenital symptoms include cervicitis, cystitis, and salpingo-oophoritis.12
- Dermatologic findings:
- Balanitis circinata - Shallow painless ulcers at meatus and glans penis; moist on uncircumcised patients; may harden and crust on circumcised patients, causing pain and scarring found in 50% of patients12
- Keratoderma blennorrhagica, found in 10% of patients12 - Hyperkeratotic skin, which begins as clear vesicles on erythematous bases and progresses to macules, papules, and nodules (found on the soles of the feet, toes, palms, scrotum, trunk, and scalp); eventually these coalesce to resemble psoriatic lesions.14 These plaques and nodules are shown in the images below.
Plaques on the soles of a patient with reactive arthritis.
Painful erosions on the fingers in a patient with reactive arthritis.
- Nail dystrophy (thickening and ridging)
- Superficial oral ulcers (30-60%),12 shown in the image below
Plaques and erosions of the tongue in a patient with reactive arthritis.
- Ophthalmologic signs:
- Conjunctivitis (most common), with mucopurulent discharge, chemosis, lid edema, and iritis
- Uveitis (12-37%), episcleritis, corneal ulcers, keratitis (4%)12
- Cardiac signs:
- Aortic regurgitation caused by inflammation of aortic wall and valve may occur. This proximal aortitis can be found in 1-2% of cases.14
- Transient conduction abnormalities are of little significance, and rarely patients may be affected with myocarditis or pericarditis.14
Causes
- Nongonococcal venereal disease, also known as endemic causes of reactive arthritis (most often due to Chlamydia) and infectious diarrhea, also known as epidemic (Shigella, Salmonella, Yersinia), precipitate reactive arthritis. Bacterial causes endemic or epidemic are mostly the result of gram-negative, obligate, or facultative intracellular pathogens.10
- The most common enteric pathogen resulting in reactive arthritis is Campylobacter (90-95% C jejuni and 5-10% C coli).9
- HLA-B27, an MHC class I molecule involved in T-cell antigen presentation, contributes to the pathogenesis of the disease and reportedly increases the risk of reactive arthritis 50-fold.14
More on Reactive Arthritis |
 Overview: Reactive Arthritis |
| Differential Diagnoses & Workup: Reactive Arthritis |
| Treatment & Medication: Reactive Arthritis |
| Follow-up: Reactive Arthritis |
| Multimedia: Reactive Arthritis |
| References |
| Further Reading |
| Next Page » |
References
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Keywords
reactive arthritis symptoms, reactive arthritis treatment, reactive arthritis causes, Reiter's syndrome, Reiter syndrome, reactive arthritis, peripheral arthritis, seronegative spondyloarthropathies, rheumatic disease, chronic arthritis
