eMedicine Specialties > Dermatology > Papulosquamous Diseases

Reactive Arthritis

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Jorge Romaní, MD, Assistant Professor, Department of Dermatology, Hospital De Palamós Faculty of Medicine, Spain; Lluís Puig, MD, PhD, Program Director, Assistant Professor, Department of Dermatology, Hospital De La Santa Creu I Sant Pau, Universitat Autónoma De Barcelona
Contributor Information and Disclosures

Updated: Jun 12, 2009

Introduction

Background

Reactive arthritis is a systemic disorder of unknown etiology that is defined by the development of psoriatic plaques, balanitis, keratoderma, conjunctivitis, urethritis, arthritis, and spondylitis.¹ This symptom complex usually follows an episode of either dysentery or urethritis.

The American Rheumatism Association criteria subcommittee defined this syndrome as 1 month of peripheral arthritis associated with urethritis, cervicitis, or both. The classic triad of the disease, namely urethritis, arthritis, and conjunctivitis, is present in only one third of the patients.

Stoll originally described this triad in 1776. In 1818, Brodie reported the triad in 5 patients. In 1916, 2 separate reports were published during World War I: Fiessinger and Leroy² detailed the findings in 4 patients (in French), and Reiter³ documented the case of a single patient with this triad of symptoms (in German). In 1942, an article by Bauer and Engelman⁴ described the first known American patient with reactive arthritis; they called this disorder, a "syndrome of unknown etiology characterized by urethritis, conjunctivitis, and arthritis (so-called Reiter's disease)." Their work contained only one reference, Reiter's article, and stated erroneously, "First described by Reiter, it has been most commonly referred to as Reiter's disease." Thus, this eponym remains in use despite its historical inappropriateness and Hans Reiter's later activities as a National Socialist war criminal.^5,6,7,8

Reactive arthritis mostly affects young men. It is frequently associated with the human leukocyte antigen B27 (HLA-B27) haplotype and is classified with the seronegative spondyloarthropathies. Reactive arthritis is preferably viewed as a tetrad, with the addition of the mucocutaneous findings of balanitis and keratoderma blennorrhagicum to the classic triad. The complete and incomplete forms of reactive arthritis can be identified by the presence or absence of the full tetrad.

Young children tend to have the postdysenteric form, whereas adolescents and young men are most likely to acquire reactive arthritis after they have urethritis. Interpreting its mucocutaneous findings as pustular psoriasis and its seronegative arthritis as psoriatic arthritis, some believe that reactive arthritis is best classified as a type of psoriasis.⁹

The eMedicine Ophthalmology article Reactive Arthritis and Rheumatology article Reactive Arthritis may be helpful.

Pathophysiology

The etiology of reactive arthritis remains uncertain. Two forms are recognized: a sexually transmitted form and a dysenteric form. Because the urethritis is a possible primary event, research efforts have focused on the identification of a microorganism that could be responsible for activating this disease. The pathophysiologic mechanism is proposed to be the triggering of an autoimmune reaction by these microorganisms.

Mycoplasma (Ureaplasma) species, Neisseria gonorrhoeae, Chlamydia species, and several viruses are among the suspected causative pathogens. Some findings have indicated that Chlamydia species are the etiologic agents in reactive arthritis.¹⁰ The discovery of Chlamydia trachomatis organisms in an involved joint and the confirmation of an immune response against Chlamydia infection (as indicated by high titers of antichlamydial antibodies in serum) have provided additional support to this hypothesis. In situ hybridization has also been used to identify chlamydial infection in synovial tissue.¹¹ Ureaplasma organisms can cause experimental and clinical nongonococcal urethritis. Synovial mononuclear cells from arthritic joints of patients with reactive arthritis react with Ureaplasma antigens; this organism has been isolated from a patient.

Reactive arthritis is also reported to occur after enteric bacterial infections, primarily those caused by parasites (Ascaris lumbricoides) and Shigella, Salmonella, Yersinia, Clostridium, and Campylobacter organisms. Impairment in the glycosaminoglycan defensive barrier was implicated in the development of reactive arthritis and reactive arthritides¹² ; this impairment may facilitate the penetration of infectious agents that are capable of triggering the autoimmune response.

The prevalence of different serotypes of C trachomatis antibodies and the incidence of C trachomatis –induced reactive arthritis was studied among patients with early arthritis in a defined population in Finland.¹³ Antibodies against C trachomatis were most common in patients with arthritis because cases with Chlamydia -induced reactive arthritis are included in this subgroup. The most accepted theory about the pathophysiology of reactive arthritis involves initial activation by a microbial antigen, followed by an autoimmune reaction that involves the skin, eyes, and joints.

Reactive arthritis has an important genetic component; it tends to cluster in certain families and almost exclusively affects males, with HLA-B27 identified in 70-80% of patients with reactive arthritis.¹³ HLA-B27 may share molecular characteristics with bacterial epitopes, facilitating an autoimmune cross-reaction instrumental in pathogenesis.

Frequency

United States

Reactive arthritis is a rare entity. Its frequency in the general population is difficult to assess. Its prevalence may be relatively high among patients with AIDS, especially men who are HLA-B27 seropositive. Reactive arthritis develops in almost 75% of HIV-positive men with HLA-B27.

A population-based study assessed reactive arthritis following culture-confirmed infections with bacterial enteric pathogens in Minnesota and Oregon.¹⁴ The estimated incidence following culture-confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella, and Yersinia infections in Oregon was 0.6-3.1 cases per 100,000 population.

International

In the United Kingdom, the incidence of reactive arthritis after urethritis is about 0.8%. Nearly 2% of Finnish males had reactive arthritis after nongonococcal urethritis; the incidence of HLA-B27 is higher among the Finnish population. Reactive arthritis develops in almost 75% of HIV-positive men with HLA-B27. Its incidence is high among patients with AIDS, and HIV testing is mandatory in patients in whom reactive arthritis is newly diagnosed, even if they do not have risk factors.

Mortality/Morbidity

Reactive arthritis can dramatically alter the patient's life because arthritis and other findings may produce considerable morbidity.

Race

Reactive arthritis affects persons of all races.

Sex

• Reactive arthritis usually affects young men.
• Reactive arthritis is uncommon in women, who represent 2-10% of patients in published series.
• A possible prostatic focus of persistent infection is postulated to explain the male predominance of reactive arthritis.

Age

• Reactive arthritis is most common in young men.
• Reactive arthritis is uncommon in children. When it occurs in children, the enteric form of the disease is predominant.

Clinical

History

A vast majority of cases of reactive arthritis are oligosymptomatic, and conjunctivitis or urethritis are present weeks before the patient's first visit, so they must be found by means of a correct anamnesis.

• Urethritis
  • An estimated 0.5-1% of cases of urethritis evolve into reactive arthritis. Urethritis develops acutely 1-2 weeks after infection through sexual contact, and is similar to gonococcal urethritis. A purulent or hemopurulent exudate appears, and the patient complains of dysuria.
  • Balanitis and vulvitis are rare in children; when they occur, they are suggestive of reactive arthritis.¹⁵
  • In men, urethritis is less painful and produces less purulent discharge than acute gonorrhea, and can go unnoticed. Findings from microscopic examination and cultures can be used to rule out N gonorrhoeae infection. Co-infection with both Chlamydia and Neisseria organisms is possible and common in some areas.
  • In women, urethritis and cervicitis may be mild, with dysuria or slight vaginal discharge, or asymptomatic, which makes diagnosis difficult.
  • Often, the initial urethritis is treated with antibiotics (especially wide-spectrum tetracyclines or macrolides) when findings suggest gonorrhea.
  • Despite an apparent early cure, the manifestations of the disease appear several weeks later, and the patient may not relate them to a prior episode of urethritis.
• Diarrhea: In enteric cases, diarrhea and dysenteric syndrome (usually mild) is followed by the clinical triad, which includes urethritis, in 1-4 weeks.
• General involvement
  • A syndrome, with malaise, low-grade fever, and generalized myalgia or headache can be present.
  • Pericarditis, aortic disease with aortic incompetence, auriculoventricular blockade, optical neuritis, pleuritis, pulmonary infiltrates, thrombophlebitis, and amyloidosis are rarely described in reactive arthritis.

Physical

• Immunoglobulin A (IgA) nephropathy: This is the most common type of primary glomerulonephritis worldwide and is reported in association with reactive arthritis.¹⁶
• Manifestations of the urogenital system
  • Circinate balanitis (see Media File 1) is characteristic. Circinate balanitis is defined by circinate or gyrate white plaques that grow centrifugally and eventually cover the entire surface of the glans penis. The penile shaft and scrotum can be involved. The lesions become rapidly keratotic in a circumcised penis.

• Circinate vulvitis is reported in women.
• Prostatitis, cystitis, and pyelonephritis are rare but possible urogenital manifestations of reactive arthritis.
• Bartholinitis can be present in women.
• Proctitis caused by Chlamydia species can occur in both sexes after anal intercourse.
• Conjunctivitis
  • Eye involvement is common.
  • Conjunctivitis appears in approximately 50% of patients with reactive arthritis.
  • Conjunctivitis is often bilateral, and it may be overlooked because of its transitory course.
  • An intense red, velvetlike conjunctival injection characterizes the conjunctivitis.
  • Edema and a purulent discharge are not rare in reactive arthritis–associated conjunctivitis.
• Other ocular manifestations
  • Iritis, iridocyclitis, and uveitis are seldom reported.
  • Iritis is more common in late recurrent episodes, and it only occurs in 3-8% of patients in the first attack.
  • At clinical examination, redness, pain, impaired vision, and exudation with hypopyon can suggest iritis.
  • Recurrent episodes can lead to pupillary synechia and glaucoma.
  • Keratitis rarely is reported.
• Arthritis
  • Articular involvement often is the key symptom of the syndrome. It is common and occurs in approximately 95% of patients.
  • The knee and tarsal joints (which support more weight than other joints) and the sacroiliac region are preferentially involved.
  • Clinically, the articular involvement resembles rheumatoid arthritis, but it is asymmetrical and commonly involves a single joint.
  • Articular swelling; intense pain; and involvement of soft tissue, fascia, and tendons occur.
  • Muscular atrophy can develop in symptomatic cases.
  • Enthesopathy (ie, inflammation at the tendinous insertion into bone) is common in reactive arthritis and in other seronegative arthritides (eg, plantar fasciitis, digital periostitis, Achilles tendinitis).
  • Sacroiliitis is commonly asymptomatic and self-limiting.
  • Early morning pain and stiffness are usually the most common manifestations.
  • Chronic spondylitis indistinguishable from ankylosing spondylitis is described in patients with reactive arthritis.
• Cutaneous involvement
  • Psoriasiform cutaneous lesions can develop weeks after urethritis in 10% of the patients. The palms and soles (see Media File 2) are most commonly involved with keratotic papules, plaques, and pustules that resemble those of pustular psoriasis.

• In some patients, typical keratoderma blenorrhagica develops 1-2 months after the onset of arthritis, with keratotic papules and plaques that are painful under pressure; sometimes, these can be disabling.
• Distal involvement with painful and erosive lesions in the tips of the fingers (see Media File 3) and toes, with pustules and subungual pustular collections, also occurs.

• Nail dystrophy is present in 20-30% of patients and often results in nail shedding.
• Erythroderma is described as a rare complication of reactive arthritis.
• Mucosal lesions
  • Erythematous macules and plaques, diffuse erythema, erosions, and bleeding can appear on the oral and pharyngeal mucosae.
  • Circinate lesions on the tongue resemble geographic tongue (see Media File 4).

• Involvement of the enteric mucosa can result in enteritis and diarrhea.
• Reactive arthritis in association with HIV infection^17,18
  • Reactive arthritis is particularly common in the context of HIV infection.
  • Patients who are HIV positive are prone to have severe psoriasiform dermatitis, which commonly involves the flexures, scalp, palms, and soles.
  • Frequently, psoriasiform dermatitis is associated with arthritis that involves the distal joints with a destructive pattern.
  • The disturbances of immune homeostasis in AIDS could account for this peculiar expression of psoriasis in these patients.
  • The existing immunodepression in patients with AIDS poses special management problems.

Causes

The etiology of reactive arthritis remains uncertain. However, 2 forms are recognized: a sexually transmitted form and a dysenteric form.

• Because urethritis is a possible primary event, research efforts have focused on identification of a microorganism that could be responsible for activating this disease.
• The pathophysiologic mechanism is thought to be a triggering of an autoimmune reaction by the microorganisms.
• Mycoplasma (Ureaplasma) species, N gonorrhoeae, Chlamydia species, and several viruses are among the suspected causative pathogens.
• Reactive arthritis triggered by adalimumab (Humira) and leflunomide (Arava) in a patient with ankylosing spondyloarthropathy and Crohn disease has been described.¹⁹
• Detection by polymerase chain reaction of C trachomatis DNA in synovial samples may be a good method to establish the diagnosis of Chlamydia -induced arthritis in patients with reactive arthritis.²⁰

• Search for CME/CE on This Topic »

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