(postdysenteric) or Chlamydia trachomatis or Mycoplasma genitourinary infections (postvenereal) [244, 245]. Although in the USA most patients have the postvenereal form of the disease, in Europe and in the rest of the world the postdysenteric form is most frequent. ReA was initially described by Hans Reiter [246] as a nonspeciÞc (nongonococal) urethritis, acute polyarthritis, and conjunctivitis, but only a minority of cases shows this classic triad. The major manifestastions are arthritis (seronegative asymmetric arthropathy, predominantly in the lower extremity), nonspeciÞc urethritis/cervicitis, inßammatory eye disease (conjunctivitis or uveitis), and mucocutaneous lesions (balanitis, oral ulceration, or keratoderma) [247].

The co-occurrence of severe ReA, psoriasis, or PA with the acquired immunodeÞciency syndrome (AIDS) emphasizes the connection between immunological factors relevant to these diseases [248Ð250].

6.1.4.1 Epidemiology

The prevalence of ReA is difÞcult to assess because of the lack of a deÞnite diagnostic test, forgotten venereal or enteric history, silent mucocutaneous lesions, overlooked eye or skin lesions, asymptomatic urethritis or cervicitis disease, AS or seronegative RA misdiagnosis, or fragmented care by subspecialty physicians. However, some studies have shown that ReA is a relatively common rheumatic disease: RS develops in about 1% of men seen at hospital clinics for nonspeciÞc urethritis, 2Ð3% of patients with Salmonella and Campylobacter enteritis, and in a higher proportion of those with Yersinia infection [244, 247]. The onset of symptoms is most frequent between the ages of 18 and 40 years. The sex distribution shows a deÞnite male predilection, but the extent of this is unclear because the diagnosis in females is more difÞcult to establish. As discussed earlier, AS occurs now more frequently in females than was previously believed, and it is likely that ReA in females will be more easily detected in the future. HLA-B27 is present in about 75Ð90% of patients with ReA and in only 6% of normal control western Caucasian populations [244, 247].

6.1.4.2 Systemic Manifestations

Articular Involvement

Arthritis is usually of acute onset, oligoarticular, asymmetric, seronegative, and often persisting or recurring [244]. It occurs within a month of onset of the enteric or genitourinary infection. Lower extremity joints, particularly the knees and the ankles, are the joints most often affected. Low back pain may occur as a result of sacroiliitis or spondylitis (Fig. 6.11). Other rheumatological manifestations involve ligaments, tendons, and fascias; they include dactylitis (sausage digits), Achilles tendinitis, plantar fasciitis or calcaneal periostitis (painful heel syndrome), and chest wall pain [244]. ReA rheumatological attacks have a mean duration of 3 months, ranging from 2 weeks to more than a year; 50% of patients will have one or more recurrences. Although complete recovery eventually occurs in most patients, those who have had persisting or recurrent attacks may develop permanent joint deformities.

Extraarticular Systemic Manifestations

Reactive arthritis patients with severe disease may have constitutional symptoms, such as fever, malaise, anorexia, and weight loss.

Genitourinary involvement occurs in ReA regardless of whether the disease follows an enteric or a genitourinary infection. The most common problem, occurring in 90% of patients, is urethritis; prostatitis, seminal vesiculitis, epididymitis, cystitis, orchitis, and urethral strictures may also occur. Urethritis is characterized by mild, serous, and transient urethral discharge, often asymptomatic; the discharge sometimes may be mucopurulent and may be accompanied by dysuria. Females may have cervicitis, nonspeciÞc vaginitis, or urethritis, all of which are usually asymptomatic [244].

Mucocutaneous lesions occur in over 50% of ReA patients. The most frequent skin lesion is circinate balanitis, which begins as painless small vesicles on the glans penis (Fig. 6.12). These lesions rupture to form superÞcial erosions, which may coalesce to form well-demarcated borders (circinate). In circumcised patients, the lesions become dry and scaly; in uncircumcised

Fig. 6.13 Keratoderma blennorrhagicum in a patient with ReiterÕs syndrome. Note the pronounced pustular and hyperkeratotic form of this dermatitis, which began approximately 3 months prior to the taking of this photograph

patients, the lesions remain moist and sometimes become secondarily infected. A less frequent although characteristic skin lesion in ReA is keratoderma blennorrhagicum (Fig. 6.13), which affects primarily soles, palms, and glans penis, and less often limbs, trunk, scrotum, and scalp [244]. It begins as small macules that evolve into papules, vesicles, or pustules that coalesce to form hyperkeratotic scaly nodules that persist for days, weeks, or months; they usually then heal without scarring but can recur. In severe cases, keratoderma blennorrhagicum may affect the whole body, with generalized exfoliation and even death [251]. Oral mucosal lesions occur in

about 10% of patients; these affect the palate, tongue, buccal mucosa, and lips. They begin as small papules that evolve into painless shallow ulcers, often with an irregular border that heals within a few days or weeks [252]. Nail involvement may occur as subungual pustules or as yellow and thickened nail plates caused by accumulation of subungual hyperkeratotic material (Fig. 6.14). Inßammatory areas of the adjacent skin may mimic paronychiae.

Other, less common extraarticular systemic manifestations include cardiac conduction abnormalities, pericarditis, aortitis, amyloidosis, thrombophlebitis, pleuritis, nonspeciÞc diarrhea, neuropathy, and meningoencephalitis [252]. As in AS, vasculitis in ReA is predominanlty a largeartery arteritis.

The presence of unusual clinical manifestations, such as seborrheic-like dermatitis (malar rash), oral thrush, hairy leukoplakia, persistent lymphadenopathy, prominent constitutional features, or rapid progression of articular manifestations, in a patient with ReA should alert the physician to the possibility of AIDS [253]. The review of systems in a patient with ReA should include information regarding sexual and drugrelated behaviors.