Chapter 147 - Postinfectious Arthritis and Related Conditions
Michael L. Miller
James T. Cassidy
Infections have been associated with arthritis during their course and as a postinfectious reaction observed several weeks or months afterward. Although certain infectious organisms have been suspected but not proved to trigger juvenile rheumatoid arthritis (JRA), other agents are often associated with a transient arthritis that does not satisfy the classification criteria for JRA. Reactive arthritis follows an infection outside the joint, particularly the gastrointestinal or genitourinary tract. The course of reactive arthritis is variable and may progress to chronic spondyloarthropathy (see Chapter 146 ). Postinfectious arthritis implies arthritis that follows infections that are usually viral in origin, with shorter duration than reactive arthritis.
Reactive arthritis may follow enteric infection with non-typhoidal Salmonella, Shigella, Yersinia enterocolitica, Campylobacter jejuni, Cryptosporidium parvum, or Giardia intestinalis, or genitourinary tract infection with Chlamydia trachomatis. Reactive arthritis may represent an autoimmune response involving T lymphocytes that cross-react to antigens in joints (molecular mimicry). A study of synovial fluid from patients with reactive arthritis suggested that T cells may be more engaged in promoting inflammation than in eliminating bacteria through cytotoxic mechanisms. However, the origin of these abnormal cells may be from outside the joint. Another possible mechanism is lymphocytic reactivity to bacterial DNA found in synovium, perhaps as a by-product of otherwise successfully cleared infection. One study of joint fluid from patients with reactive arthritis, using polymerase chain reaction amplification, demonstrated bacterial DNA. However, a relationship to specific clinical characteristics was not found.
Several viruses (rubella, varicella-zoster, herpes simplex, and cytomegalovirus) have been isolated from the joint space. Antigens from other viruses (hepatitis B, adenovirus 7) have been identified in immune complexes from joint tissue. Postinfectious arthritis following viral infections appears to involve the deposition in joints of immune complexes containing viral antigens.
Certain HLA types may predispose to development of reactive arthritis, possibly by triggering autoreactive T lymphocytes. Adolescents and adults with reactive arthritis following enteric infections have shown persistent gut inflammation even after resolution of gastrointestinal manifestations, particularly in HLA-B27-positive individuals. Uveitis complicating reactive arthritis to Y. enteritis has also been associated with HLA-B27. Some children, often HLA-B27 positive, with reactive arthritis eventually develop spondyloarthropathy, further suggesting that HLA type predisposes to reactive arthritis.
Bacterial enteritis caused by Shigella, Salmonella, Yersinia, and Campylobacter can be followed within days to several weeks by the development of arthritis and sometimes enthesitis, or inflammation of the muscular or tendinous attachment to bone, in a syndrome similar to and overlapping spondyloarthropathy (see Chapter 146 ). Although the erythrocyte sedimentation rate (ESR) may be elevated, fever and leukocytosis are often absent. Urethritis and conjunctivitis develop occasionally. Postinfectious arthritis following less apparent illness, such as viral upper respiratory tract infections, may precede arthralgia and arthritis by 1–2 mo. Symptoms of arthralgia and joint swelling are transient, usually lasting less than 6 wk.
Certain viruses associated with arthritis ( Box 147–1 ) may result in particular patterns of joint involvement. Rubella and hepatitis B virus typically affect the small joints, and mumps and varicella often involve large joints, especially the knees. The hepatitis B arthritis-dermatitis syndrome is characterized by rash and arthritis resembling serum sickness. Rubella-associated arthropathy follows natural rubella infection and, infrequently, rubella immunization. It typically occurs in young women, with increased incidence with advancing age, and is uncommon in preadolescent children and in males. Arthralgias of the knees and hands usually begin within 7 days of onset of the rash or 10–28 days after immunization. Parvovirus B19, responsible for erythema infectiosum (fifth disease), can cause arthralgia, symmetric joint swelling, and morning stiffness in adults, particularly women, and less frequently in children. Arthritis occurs occasionally during cytomegalovirus infection and may occur during varicella infections, and is rare after Epstein-Barr virus infection. Varicella may also be complicated by suppurative arthritis, usually due to group A Streptococcus.
Arthritis has been reported in children with severe truncal acne, usually in male adolescents. Patients often have fever and superficial infection of skin lesions. Recurrent episodes may be associated with myopathy and may last for several months. Infective endocarditis can be associated with arthralgia, arthritis, or signs suggestive of vasculitis, such as Osler nodes, Janeway lesions, and Roth spots. Arthritis also occurs in children with Mycoplasma pneumoniae infections.
Poststreptococcal arthritis may follow infection with either group A or group G Streptococcus. Because valvular lesions have been documented by echocardiography after the acute illness in some of these children, some clinicians consider this to be an incomplete form of acute rheumatic fever (see Chapter 168.1 ). Certain HLA-DRB1 types may predispose children to develop either poststreptococcal arthritis or classic rheumatic fever. Poststreptococcal arthritis is pauciarticular, may affect the small and large joints, and persists for months, compared with the
Box 147-1. Viruses Associated with Arthritis
Variola virus (smallpox)
Adapted from Cassidy JT, Petty RE: Arthritis related to infection. In Textbook of Pediatric Rheumatology. Philadelphia, WB Saunders, 1995, p 503.
typical course of migratory polyarthritis of rheumatic fever. The symptoms are usually mild and tend to resolve completely.
Transient synovitis (toxic synovitis) typically affects the hip joints, often after an upper respiratory tract infection. Boys from 3–10 yr of age are most commonly affected and have complaints of pain in the hip, thigh, or knee. The ESR and white blood cell count are usually normal. Radiologic or ultrasound examination may reveal widening of the joint space of the hip. Aspiration of the hip may be necessary to exclude suppurative arthritis. The cause of this relatively common syndrome is not known, but it is presumed to be a viral or postinfectious arthritis.
The diagnosis of reactive postinfectious arthritis is usually established by exclusion only after the arthritis has resolved. Acute arthritis affecting a single joint suggests suppurative arthritis; osteomyelitis may cause joint pain but is associated more often with focal bone pain over the site of infection. Arthritis associated with gastrointestinal symptoms or elevated liver function test results may be caused by infectious or autoimmune hepatitis. Arthritis or spondylarthritis may occur in some children with inflammatory bowel disease, either Crohn disease or chronic ulcerative colitis (see Chapter 317 ). When two or more blood cell lines show a progressive decrease in a child with arthritis, parvovirus infection, macrophage activation syndrome, and leukemia should be considered. Persistent arthritis suggests the possibility of rheumatic disease, including JRA, spondyloarthropathy, and systemic lupus erythematosus.
No specific treatment is necessary for reactive arthritis, except for relief of pain and the functional limitations of arthritis with nonsteroidal anti-inflammatory agents. If swelling or arthralgia recurs, further evaluation may be necessary to preclude active infection or evolving rheumatic disease, such as spondyloarthropathy, JRA, or systemic lupus erythematosus.
Complications and Prognosis.
Postinfectious arthritis following viral infections usually resolves without complications unless it is part of a severe viral infection affecting other organs, as with encephalomyelitis. Reactive arthritis, especially after bacterial enteric infection or genitourinary tract infection with C. trachomatis, has the potential for evolving to a chronic arthritis and spondyloarthropathy (see Chapter 146 ). Children with reactive arthritis following enteric infections occasionally develop inflammatory bowel disease months to years after onset. Both uveitis and carditis have been reported in some children diagnosed with reactive arthritis.