Dermatologic Manifestations of Reactive Arthritis 

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 image below depicts erosive lesions in the tips of the fingers in a patient with reactive arthritis.

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 Leroy^[2] detailed the findings in 4 patients (in French), and Reiter^[3] documented the case of a single patient with this triad of symptoms (in German). In 1942, an article by Bauer and Engelman^[4] 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 Medscape Reference Ophthalmology article Reactive Arthritis and Rheumatology article Reactive Arthritis may be helpful.

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 arthritides^[12] ; 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.

The annual incidence and prevalence of psoriatic arthritis, ankylosing spondylitis, and reactive arthritis was estimated in a sample of the Czech population.^[15] The annual incidence of reactive arthritis in adults was found to be 9.3 cases per 100,000 population; its prevalence was 91.3 cases per 100,000 population.

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.