Ankylosing spondylitis

Abstract

The term spondyloarthritis (SpA) covers several clinically and genetically linked subtypes including ankylosing spondylitis (AS), the most severe form of SpA that is characterized by spinal pain, stiffness, and new bone formation which appears in the form of syndesmophytes and ankylosis in the spinal column. Patients with AS do frequently have extra-articular manifestations (EAM) such as anterior uveitis, psoriasis, and colitis, similar to the chronic inflammatory bowel diseases. In addition, different comorbidities have been observed to occur frequently in AS patients. Indeed, the risk to develop cardiovascular disease (CVD), infections, and osteoporosis is reportedly higher in AS patients than in the general population - especially in those with long-standing disease and periods of persistently high disease activity. There is some evidence that gastrointestinal and renal comorbidities as well as depression occur more frequently in patients with AS. The increased mortality of AS patients is largely due to CVD which is the most frequent cause of death (40.0%). The excess mortality risk is probably multifactorial, being related to both chronic systemic inflammation and a higher prevalence of conventional, mainly cardiovascular risk factors. There is some evidence that tumor necrosis factor inhibitors (TNFi) may reduce CV morbidity and mortality in patients with AS. Osteopenia and osteoporosis are the most frequent comorbidities in AS. Accordingly, a decreased bone mineral density (BMD) is found in 19-62% of cases in cross-sectional studies - the broad range largely coming from differences in inclusion criteria. Importantly, the risk of vertebral fractures increased by six- to eightfold in patients with AS. When assessed systematically, even multiple vertebral fractures are often detected, many of which had not been clinically symptomatic. Although TNFi decreases inflammation and has shown to be also effective in increasing BMD, no reduced risk to develop vertebral fractures has been demonstrated to date. This may be explained by the multifactorial nature of the increased fracture risk in the spinal column that is not only osteoporotic but also due to a stiff and fused spine. Malignant (26.8%) and infectious (23.2%) diseases are also frequent causes of morbidity and mortality. In contrast, malignancies (solid tumors and lymphomas) are responsible for the excess mortality in AS patients. The slightly increased risk of (severe) infections is largely due to treatment with immunosuppressive drugs. However, the prevalence and incidence of infections such as hepatitis and tuberculosis and the performance of current screening and prevention strategies show a large variety worldwide. The overall perception is that comorbidities such as CVD and infections are not optimally managed in patients with rheumatic diseases including those with AS. Finally, data on how to best manage osteoporosis in patients AS is lacking.