Reactive arthritis, previously known asReiter's syndrome,[1] is a form ofinflammatoryarthritis[2] that develops in response to aninfection in another part of the body (cross-reactivity). Coming into contact withbacteria and developing an infection can trigger the disease.[3] By the time a person presents with symptoms, the "trigger" infection has often been cured or is inremission in chronic cases, thus making determination of the initial cause difficult.
The manifestations of reactive arthritis include the following triad of symptoms: inflammatory arthritis of large joints, inflammation of the eyes in the form ofconjunctivitis oruveitis, andurethritis in men orcervicitis in women. Arthritis occurring alone following sexual exposure or enteric infection is also known as reactive arthritis. Affected people may present with mucocutaneous lesions, as well aspsoriasis-like skin lesions such ascircinate balanitis, andkeratoderma blennorrhagicum.Enthesitis can involve the Achilles tendon resulting in heel pain.[4] Not all affected persons have all the manifestations.
The clinical pattern of reactive arthritis commonly consists of aninflammation of fewer than five joints which often includes the knee orsacroiliac 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).[5][6]
It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and is more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population.[11][12] It can occur in epidemic form. Patients withHIV have an increased risk of developing reactive arthritis as well.
Numerous 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 asFiessenger–Leroy–Reiter syndrome.[13]
Keratoderma blennorrhagicum due to reactive arthritis
Because common systems involved include the eye, the urinary system, and the hands and feet, one clinicalmnemonic in reactive arthritis is "Can't see, can't pee, can't climb a tree."[14]
The classic triad consists of:
Conjunctivitis
Nongonococcal urethritis
Asymmetric oligoarthritis
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 increasedfrequency of urination. Other urogenital problems may arise such asprostatitis in men andcervicitis,salpingitis, and/orvulvovaginitis in women.
It presents with monoarthritis affecting the large joints such as theknees and sacroiliac spine causingpain andswelling. An asymmetrical inflammatoryarthritis of interphalangeal joints may be present but with relative sparing of small joints such as the wrist and hand.
Patient can have enthesitis presenting as heel pain, Achilles tendinitis, orplantar fasciitis, along withbalanitis circinata (circinate balanitis), which involves penile lesions present in roughly 20 to 40 percent of the men with the disease.
A small percentage of men and women develop small hardnodules calledkeratoderma blennorrhagicum on the soles of the feet and, less commonly, on the palms of the hands or elsewhere. The presence of keratoderma blennorrhagica is diagnostic of reactive arthritis in the absence of the classical triad. Subcutaneous nodules are also a feature of this disease.
Ocular involvement (mild bilateral conjunctivitis) occurs in about 50% of men with urogenital reactive arthritis syndrome and about 75% of men with enteric reactive arthritis syndrome.Conjunctivitis anduveitis 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.
Dactylitis, or "sausage digit", a diffuse swelling of a solitary finger or toe, is a distinctive feature of reactive arthritis and other peripheralspondylarthritides but can also be seen in polyarticulargout andsarcoidosis.
Some patients experience serious gastrointestinal problems similar to those ofCrohn's disease.
About 10 percent of people with reactive arthritis, especially those with a prolonged course of the disease, will develop cardiac manifestations, includingaortic regurgitation andpericarditis. Reactive arthritis has been described as a precursor of other joint conditions, includingankylosing spondylitis.
Reactive arthritis is associated with theHLA-B27 gene on chromosome 6 and by the presence ofenthesitis as the basic pathologic lesion[16] and is triggered by a precedinginfection. The most common triggering infection in the US is a genital infection withChlamydia trachomatis. Other bacteria known to cause reactive arthritis which are more common worldwide areUreaplasma urealyticum,Salmonella spp.,Shigella spp.,Yersinia spp., andCampylobacter spp.[17] A bout offood poisoning or agastrointestinal infection may also precede the disease (the last fourgenera of bacteria mentioned above are enteric bacteria).[18]Shigella is the most common organism causing reactive arthritis following diarrhea.Chlamydia trachomatis is the most common cause of reactive arthritis following urethritis.Ureaplasma andmycoplasma are rare causes. There is some circumstantial evidence for other organisms causing the disease, but the details are unclear.[18]
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 autoimmune response involving cross-reactivity of bacterial antigens with joint tissues or by bacterial antigens that have somehow become deposited in the joints.[citation needed]
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.
Tests forC-reactive protein anderythrocyte sedimentation rate are non-specific tests that can be done to corroborate the diagnosis of the syndrome.A blood test for the genetic markerHLA-B27 may also be performed. About 75 percent of all patients with reactive arthritis have this gene.
The main goal of treatment is to identify and eradicate the underlying infectious source with the appropriateantibiotics if still present. Otherwise, treatment is symptomatic for each problem. Nonspecific urethritis may be treated with a short course oftetracycline.Analgesics, particularlyNSAIDs, are used.Steroids,sulfasalazine andimmunosuppressants may be needed for patients with severe reactive symptoms that do not respond to any other treatment. Localcorticosteroids are useful in the case ofiritis.[citation needed]
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 involve 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 disablingarthritis,heart disease,amyloid deposits,ankylosing spondylitis,immunoglobulin Anephropathy, cardiac conduction abnormalities, oraortitis withaortic regurgitation.[20] However, most people with reactive arthritis can expect to livenormal life spans and maintain a near-normal lifestyle with modest adaptations to protect the involved organs.
Because women may be underdiagnosed, the exact incidence of reactive arthritis is difficult to estimate. A few studies have been completed, though. InNorway between 1988 and 1990, the incidence was 4.6 cases per 100,000 for chlamydia-induced reactive arthritis and 5 cases per 100,000 for that induced byenteric bacteria.[21] In 1978 inFinland, the annual incidence was found to be 43.6 per 100,000.[22]
When reactive arthritis appears in a triad that also includes ophthalmic and urogenital manifestations, theeponym "Reiter's syndrome" is often applied;[citation needed] German physicianHans Conrad Julius Reiter described the condition in a soldier he treated duringWorld War I.
Many physicians have suggested that the eponym is undeserved. Reiter'sNazi Party affiliation, and in particular his involvement in forced human experimentation in theBuchenwald concentration camp (which, after his capture at the end ofWorld War II, resulted in hisprosecution in Nuremberg as awar 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.[23]
^Watson Buchanan, W; Kean, Walter F; Rainsford, K D; Kean, Colin A (February 2024). "Reactive arthritis: the convoluted history of Reiter's disease".Inflammopharmacology.32 (1):93–99.doi:10.1007/s10787-023-01336-4.PMID37805646.
^Geirsson AJ, Eyjolfsdottir H, Bjornsdottir G, Kristjansson K, Gudbjornsson B (May 2010). "Prevalence and clinical characteristics of ankylosing spondylitis in Iceland – a nationwide study".Clinical and Experimental Rheumatology.28 (3):333–40.PMID20406616.
^Harrison's Rheumatology, Second Edition [Anthony Fauci, Carol Langford], Ch.9 THE SPONDYLOARTHRITIDES, Reactive Arthritis, page.134
^Zadik Y, Drucker S, Pallmon S (August 2011). "Migratory stomatitis (ectopic geographic tongue) on the floor of the mouth".J Am Acad Dermatol.65 (2):459–60.doi:10.1016/j.jaad.2010.04.016.PMID21763590.
^Hill Gaston JS, Lillicrap MS (2003). "Arthritis associated with enteric infection".Best Pract Ice & Research. Clinical Rheumatology.17 (2):219–239.doi:10.1016/S1521-6942(02)00104-3.PMID12787523.
^abPaget, Stephen (2000).Manual of Rheumatology and Outpatient Orthopedic Disorders: Diagnosis and Therapy (4th ed.). Lippincott, Williams, & Wilkins. pp. chapter 36.ISBN978-0-7817-1576-8.
^Kvien, T.; Glennas, A.; Melby, K.; Granfors, K; et al. (1994). "Reactive arthritis: Incidence, triggering agents and clinical presentation".Journal of Rheumatology.21 (1):115–22.PMID8151565.
^Isomäki, H.; Raunio, J.; von Essen, R.; Hämeenkorpi, R. (1979). "Incidence of rheumatic diseases in Finland".Scandinavian Journal of Rheumatology.7 (3):188–192.doi:10.3109/03009747809095652.PMID310157.
