In these conditions arthritis is associated with inflammation that affects the spine and lumbosacral joints (ankylosing spondylitis), the urethra (Reiter’s syndrome), the skin (psoriasis), or the intestinal tract. These conditions were (and are) frequently referred to as “rheumatoid arthritis variants.” This name has been discarded by most rheumatologists because the diseases have relatively little in common with classic RA except for involvement of joints and are considered separate entities. As a group they have certain similarities. There frequently is a component of inflammation at the attachment of ligaments to bone (enthesiopathy) rather than only synovial involvement. Except for ankylosing spondylitis, they are found in association with other well-known diseases, and there is a tendency for spine and large joint involvement in a minority of cases. Spondylitis develops in about 5%-10% of patients with inflammatory bowel arthritis, in about 20% of patients with psoriatic arthritis, and in more than 50% of those with the chronic form of Reiter’s syndrome. Iritis is common in patients with spondylitis, and conjunctivitis is a typical feature of Reiter’s syndrome. The RA test results are usually negative. There is a hereditary component and an increased incidence of HLA-B27. Overall, about 10%-20% of persons with HLA-B27 antigen will develop some form of spondyloarthritis; the rate is said to reflect a genetic relationship, with a 25%-50% risk for those with close relatives who are also HLA-B27 positive but only a 2%-10% risk in those without such relatives.

Ankylosing spondylitis. Ankylosing spondylitis (Marie-Strumpell disease) involves primarily the spine and sacroiliac joints, with peripheral joint arthritis present in about 30% of cases. Iritis may develop in 30%-40% of cases. The incidence in Afro-Americans is much less than in Europeans. Males are predominantly affected. Mild anemia is found in about 25%. The ESR is elevated in 80%-90% of those with active disease. HLA-B27 is present in more than 90% of affected persons. Since HLA-B27 is found in 6%-7% of Europeans and in 3%-4% of Afro-Americans and the incidence of ankylosing spondylitis is about 1 in 1,000 of the general population, most persons who have positive HLA-B27 results do not have ankylosing spondylitis. Since HLA-B27 is found in about 92% of patients (literature range 83%-98%), absence of HLA-B27 in Europeans is some evidence against the diagnosis in clinically borderline cases.

Psoriatic arthritis. Psoriatic arthritis most commonly involves the distal interphalangeal joints of the hands and feet, although the spine or pelvis is affected in about 20% of cases. HLA-B27 is found in about 35% of cases (literature range, 20%-90%, the higher percentages being found when spondylitis was present). About 10% (range, 5%-20%) of patients with psoriasis develop psoriatic arthritis.

Reiter’s syndrome. Reiter’s syndrome typically consists of joint, urethral, mucocutaneous, and eye lesions. These are manifested by a (usually) self-limited nongonococcal urethritis found predominantly in males that may be accompanied by conjunctivitis or iritis and by mucocutaneous ulcers or other lesions. The disease may appear spontaneously, may follow a gonococcal infection (possibly due to concurrent Chlamydia or Mycoplasma infection) or may be precipitated by genitourinary or colon infection. Shigella infection is followed by Reiter’s syndrome in 1%-2% of cases. About 85% (range, 63%-100%) of Europeans with Reiter’s syndrome have the HLA-B27 antigen. The arthritic component primarily involves the lower extremities and may be accompanied by tendinitis. However, spondylitis is said to develop in 50% or more patients with the chronic form of Reiter’s syndrome. Behзet’s syndrome (oral and genital ulceration, iritis, and arthritis) may mimic some components of Reiter’s syndrome. Reiter’s syndrome may occur in females, in which case the urethritis component may not be recognized.

Arthritis associated with inflammatory bowel disease. Inflammatory bowel disease may be accompanied by peripheral arthritis and by spondylitis. The two types of arthritis behave independently of each other, although either type may be present or the two may coexist. Twelve percent to 20% of patients with ulcerative colitis or regional enteritis (Crohn’s disease) develop asymptomatic peripheral joint arthritis. This is not strongly associated with the HLA-B27 antigen. The knee and ankle are most frequently involved. Spondylitis is said to occur in about 5% (range, 1%-6%) of patients with chronic inflammatory bowel disease, and sacroiliitis in about 15%. HLA-B27 is reported in about 60% of those with spondylitis (literature range, 37%-75%). Iritis is also more common in these patients. Therefore, the arthritis of inflammatory bowel disease in some patients has similarities in several respects to Reiter’s syndrome except for lack of urethritis. Whipple’s disease may also be associated with arthritis.

Reactive arthropathies. This group partially overlaps the “seronegative spondyloarthropathies” (Reiter’s syndrome traditionally being in both categories), but differs in that each has an infectious or inflammatory etiology as well as a secondary arthritic component. This group includes Reiter’s syndrome, ulcerative colitis and Crohn’s disease (“enteropathic arthropathies”), infection by certain gastrointestinal (GI) tract pathogens (with arthritis but without direct joint infection), and acute rheumatic fever. Although the category of reactive arthropathies is most often restricted to infection by the GI tract pathogens, there is sufficient overlap with various aspects of the conditions I have discussed that it seems reasonable to include them here.

Arthritis associated with enteric pathogens. Arthritis in these patients appears abruptly 1-4 weeks after a GI tract infection subsides (range, 1 week after onset of infection to 6 weeks after end of the infection). Peripheral joints are predominately (but not exclusively) involved. About 60%-80% of patients are positive for HLA-B27 antigen. Infections that risk developing “reactive arthritis” in HLA-B27 patients, in descending order, are Salmonella (1%-2% of patients), Shigella, Campylobacter jejuni, and Yersinia.

Diagnosis in these diseases involves exclusion of RA (RF screening test) and SLE (ANA test). If these tests are negative, serologic tests for arthritis-related enteric bacteria would be necessary. These would probably have to be sent to a large reference laboratory. Stool culture would usually be negative (except for a few chronic carriers) since arthritis symptoms generally do not begin until after the enteric infection ends. Elevated antibody titers do not differentiate between those with nonarthritic and those with arthritic conditions. For Yersinia, IgM or IgA antibody titers are the most useful, but the reported sensitivity of these tests varies widely (38%-95%). For Campylobacter, IgM and IgA antibodies are also used, with reported sensitivity of about 75%. Flagellar IgM antibody assay was found to be 85% sensitive in one study. Salmonella antibody tests are discussed in the chapter on microbiology; the Widal test is unreliable and current immunoassay tests reported in the literature mostly use homemade reagents. Shigella IgM and IgA immunosassay tests have been reported but also are homemade in research settings.

Other infections. Infection by Borellia burgdorferi (Lyme disease) has a prominant arthritic component that occurs later in the course of illness. Lyme disease and its serologic tests are discussed in the chapter on spirochetal diseases. Several virus infections may cause arthritis, notably hepatitis virus B and parvovirus. These are discussed in the chapter on virus diseases. I am also including acute rheumatic fever in this group, although traditionally it has usually been loosely associated with the rheumatoid-collagen diseases.