Chapter 287 THE SPONDYLOARTHROPATHIES

John J. Cush

Peter E. Lipsky

The spondyloarthropathies are a heterogeneous group of disorders that share a number of clinical, radiographic, and genetic features. These disorders include ankylosing spondylitis, Reiter's syndrome, reactive arthritis, psoriatic arthritis, and the enteropathic arthropathies.

The spondyloarthropathies share a constellation of characteristic clinical, radiographic, and immunogenetic manifestations that suggest a common or related etiopathogenesis (Table 287-1) . Distinctive features include a propensity for axial arthritis (sacroiliitis and spondylitis); peripheral arthritis (often asymmetrical and oligoarticular); inflammation at tendinous, ligamentous, or fascial insertions (enthesitis); and a familial pattern of inheritance based on the presence of the class I major histocompatibility complex (MHC) antigen HLA-B27. These disorders can manifest extra-articular features that suggest a particular spondyloarthropathy. Extra-articular manifestations may involve periarticular structures (enthesitis), eyes (conjunctivitis, uveitis), the gastrointestinal tract (oral ulcerations, asymptomatic gut inflammation), the genitourinary tract (urethritis prostatitis, cervitis), the heart (aortitis, heart block), skin (keratoderma blennorrhagicum), or nails (onycholysis, nail pitting). Often, patients will demonstrate overlapping features of more than one condition or will be HLA-B27+ and possess a constellation of symptoms that do not meet the strigent diagnostic criteria of a particular spondyloarthropathy. In such patients the more generic term "spondyloarthropathy" may be more accurate. This distinction allows the clinician to approach these conditions as a group of related disorders and permits the early diagnosis and treatment of affected individuals (Fig. 287-1) .

New diagnostic criteria for the spondyloarthropathies have been proposed (Table 287-2) because previous diagnostic criteria have been shown to exclude many patients with spondyloarthropathy. The broader definitions used these criteria allow for earlier diagnosis and more liberal inclusion of many patients with spondyloarthropathy.

HLA-B27.

The human leukocyte class I MHC antigen HLA-B27 was first linked with ankylosing spondylitis in 1973. This genetic marker is found in nearly 8% of North American white individuals. The actual risk of ankylosing spondylitis developing in an HLA-B27+ person is estimated to be 1 to 2%. A reactive arthropathy will develop in only 20% of HLA-B27+ individuals infected with arthritogenic bacteria (Table 287-3) . Moreover, in only 20% of HLA-B27+ first-degree relatives of HLA-B27+ spondylitis patients will ankylosing spondylitis develop, which suggests that factors other than HLA-B27 must play a crucial role in determining disease susceptibility. The prevalence of HLA-B27 varies greatly among different ethnic groups. A higher prevalence is seen in the Haida and Pima Indians, and the lowest prevalence is seen among Africans and Asians. When North American whites are compared with blacks, HLA-B27 is found in 90 versus 60% of those with ankylosing spondylitis and 75 versus 50% of those with Reiter's syndrome, respectively.

Seven serologically defined subtypes of HLA-B27 have been defined, and six of these (B*2701, B*2702, B*2703, B*2704, B*2705, and B*2707) are associated with ankylosing spondylitis. Other class I MHC antigens are termed the HLA-B27 cross-reactive antigens and include HLA-B7, Bw22, -B39, -B40, -B42, and -B60, which are often present in HLA-B27-patients with spondyloarthropathy.

HLA-B27 has shown to influence disease expression for most of the spondyloarthropathies, especially those with Reiter's syndrome. HLA-B27+ individuals are more likely to have an earlier disease onset, sacroiliitis, spondylitis, a severe clinical course, or acute anterior uveitis. By contrast, in HLA-B27- patients, peripheral arthropathy, skin and nail disease, and inflammatory bowel disease or undifferentiated spondyloarthropathy are more likely to develop.

Strong evidence for the role of HLA-B27 in disease pathogenesis has been derived from experiments in which human HLA-B27 has been transfected into rats. Typical features of spondyloarthropathy, including gut inflammation, spondylitis, peripheral arthritis, psoriasiform skin and nail changes, uveitis, and orchitis, spontaneously develop in these transgenic rats. The role of environmental factors in disease pathogenesis is emphasized by the observation that many of these features do not develop when these animals are bred in a germ-free environment.

ANKYLOSING SPONDYLITIS.

Ankylosing spondylitis is the most common inflammatory disorder of the axial skeleton. Epidemiologic studies have suggested that the prevalence of ankylosing spondylitis in a white population is 0.02 to 0.23%. Ankylosing spondylitis commonly affects young men more frequently than women, with an estimated male-female ratio ranging from 2.5 to 5:1. Ankylosing spondylitis in women is often underdiagnosed, primarily because of milder axial disease and occult extra-articular manifestations. Women with ankylosing spondylitis tend to have a delayed disease onset, less hip involvement, less aggressive axial disease, more peripheral arthritis, severe osteitis pubis, and a higher incidence of isolated cervical spine disease.

Ankylosing spondylitis often begins in young adulthood. Up to 15% of children with juvenile chronic arthritis are classified with juvenile spondylitis. These children between ages 9 and 16 are often HLA-B27+ and manifest low back pain or an asymmetrical oligoarthritis years before fully expressed spondyloarthropathy develops. In contrast, late-onset spondyloarthropathy has been described in several HLA-B27+ individuals older than 50 years, in whom sacroiliitis (without spondylitis), oligoarticular arthritis, an elevated erythrocyte sedimentation rate, and evidence of skeletal hyperostosis developed.