Recent advances in the treatment of the seronegative spondyloarthropathies.

The observation that anti-tumor necrosis factor (anti-TNF) therapies dramatically reduce joint pain and inflammation and retard radiographic progression in rheumatoid arthritis (RA) has created a considerable amount of enthusiasm among rheumatologists and has set new treatment standards for patients with inflammatory joint disease. A central question that has emerged is whether these agents are effective in treating the seronegative spondyloarthropathies (SpA). A related question is whether second-line agents such as methotrexate (MTX) can improve axial inflammation and functional measures if administered early in disease. The SpA are a cluster of inflammatory arthridites encompassing ankylosing spondylitis (AS), psoriatic arthritis (PsA), Reiter's syndrome/reactive arthritis (ReA), and the arthritis associated with inflammatory bowel disease. These disorders share similar clinical and immunogenetic features including axial arthritis and enthesopathy, a general predilection for males and patients positive for the MHC class I alleles, the absence of rheumatoid factor, and association with infections of the intestinal and genitourinary tracts. Reclassification of SpA based on axial or peripheral involvement may be more relevant from a pathophysiologic and therapeutic perspective than the current stratification, given the strong association between axial disease and the HLAB27 allele and the relative resistance of axial disease to conventional anti-inflammatory therapy.