Reactive and Postinfectious Arthritis

Pathogenesis

Reactive arthritis typically follows enteric infection with Salmonella species, Shigella flexneri, Yersinia enterocolitica, Campylobacter jejuni , or genitourinary (GU) tract infection with Chlamydia trachomatis . Escherichia coli and Clostridium difficile are also causative enteric agents, although less common (see Table 181.2 ). Acute rheumatic fever caused by group A streptococcus (see Chapters 182 and 210.1 ), arthritis associated with infective endocarditis (see Chapter 464 ), and the tenosynovitis associated with Neisseria gonorrhoeae are similar in some respects to reactive arthritis.

Approximately 75% of patients with reactive arthritis are HLA-B27 positive. Incomplete elimination of bacteria and bacterial products, such as DNA, has been proposed as a factor in reactive arthritis. A relationship with clinical characteristics of specific infectious disorders is not present. In postinfectious arthritis, several viruses (rubella, varicella-zoster, herpes simplex, cytomegalovirus) have been isolated from the joints of patients. Antigens from other viruses (e.g., hepatitis B, adenovirus) have been identified in immune complexes from joint tissue.

Patients with reactive arthritis who are HLA-B27 positive have an increased frequency of acute and symptomatic uveitis and other extraarticular features. In addition, HLA-B27 is a risk factor for persistent gastrointestinal (GI) inflammation following enteric infections, even after resolution of the initial infection, and significantly increases the risk that the individual will develop chronic spondyloarthritis. Nevertheless, reactive arthritis also occurs in HLA-B27–negative patients, emphasizing the importance of other genes in disease susceptibility.

Clinical Manifestations and Differential Diagnosis

Symptoms of reactive arthritis begin approximately 3 days to 6 wk following infection. The classic triad of arthritis, urethritis, and conjunctivitis is relatively uncommon in children. The arthritis is typically asymmetric, oligoarticular, with a predilection for lower extremities. Dactylitis may occur, and enthesitis is common, affecting as many as 90% of patients ( Fig. 182.1 ). Cutaneous manifestations can occur and may include circinate balanitis, ulcerative vulvitis, erythematous oral macules or plaques or erosions, erythema nodosum, paronychia, painful erosions or pustules on fingertips, and keratoderma blennorrhagica, which is similar in appearance to pustular psoriasis ( Fig. 182.2 ). Systemic symptoms may include fever, malaise, and fatigue. Less common features may include conjunctivitis, optic neuritis, aortic valve involvement, sterile pyuria, and polyneuropathy. Early in the disease course, markers of inflammation—erythrocyte sedimentation rate (ESR), C-reactive protein, and platelets—may be greatly elevated. The clinical manifestations may last for weeks to months.

Familiarity with other causes of postinfectious arthritis is vital when a diagnosis of reactive arthritis is being considered. Numerous viruses are associated with postinfectious arthritis and may result in particular patterns of joint involvement ( Table 182.1 ). Rubella and hepatitis B virus typically affect the small joints, whereas mumps and varicella often involve large joints, especially the knees. The hepatitis B arthritis–dermatitis syndrome is characterized by urticarial rash and a symmetric migratory polyarthritis resembling that of serum sickness. Rubella-associated arthropathy may follow natural rubella infection and, infrequently, rubella immunization. It typically occurs in young women, with an increased frequency with advancing age, and is uncommon in preadolescent children and in males. Arthralgia of the knees and hands usually begins within 7 days of onset of the rash or 10-28 days after immunization. Parvovirus B19, which is responsible for erythema infectiosum (fifth disease), can cause arthralgia, symmetric joint swelling, and morning stiffness, particularly in adult women and less frequently in children. Arthritis occurs occasionally during cytomegalovirus infection and may occur during varicella infections but is rare after Epstein-Barr virus infection. Varicella may also be complicated by suppurative arthritis, usually secondary to group A streptococcus infection. HIV is associated with an arthritis that resembles psoriatic arthritis more than JIA (see Chapter 180 ).