Ankylosing spondylitis: Interaction between genes, joints, age at onset, and disease expression

Objective. Ankylosing spondylitis (AS) is a chronic inflammatory disorder w ith symptom onset generally occurring in the late teens/mid-twenties. In wo men, a younger age at onset enhances disease susceptibility in the next gen eration. We examined the influence of age at symptom onset on phenotypic ex pression. Methods. Patients were divided into cohorts according to age of symptom ons et. The primary outcome measure was radiological progression (by Bath AS Ra diology Index, BASRI). Secondary measures were disease activity (Bath AS Di sease Activity Index, BASDAI), function (Bath AS Functional Index, BASFI), numbers undergoing AS related surgery, and percentage with secondary disord ers. Results. Age at onset had no significant effect on radiological progression (young onset vs late onset, 8.0, 8.6, respectively) disease activity (youn g vs late, 4.4, 4.4), need for non-hip surgical intervention (9%, 8%, respe ctively), or prevalence of secondary disorders (iritis, 40%, 41%; psoriasis , 20%, 19%; inflammatory bowel disease, 7.5%, 8.9%). By contrast, there was a striking increase in prevalence of total hip replacement in those with j uvenile onset (18%, 8%, respectively; p < 0.001). Regardless of age at onse t, spinal progression determined radiologically was greater in those with h ip arthritis compared to those without [young onset hip involvement vs non- hip involvement, 9.7 (2.4), 7.2 (3.0) (p < 0.001); late onset hip involveme nt vs non-hip involvement, 10.1 (2.5), 7.1 (3.0), respectively]. Function d eteriorates with age (young onset vs late onset, 3.7, 4.5, respectively; p < 0.01). Conclusion. (1) Hip disease (young or late onset) is a major prognostic mar ker for longterm severe disease (patients with hip disease have a spinal sc ore increased by 2.5-3 points or 35-40% more change). (2) Hip involvement i s more prevalent among patients with young age at onset. (3) Young onset pa tients without hip involvement do not have more severe disease. Thus, age a t onset, itself, does not influence disease severity. (4) Since hip involve ment and not age at onset is associated with worse outcome, patients with a young age at onset may be assumed to have an increased susceptibility load (i.e., genetic component or environmental trigger) rather than more severi ty genes. The lack of association between severity and age at onset implies that the determinants of susceptibility and severity are independent.