Ankylosing spondylitis: interaction between genes, joints, age at onset, and disease expression.
OBJECTIVE
Ankylosing spondylitis (AS) is a chronic inflammatory disorder with symptom onset generally occurring in the late teens/mid-twenties. In women, a younger age at onset enhances disease susceptibility in the next generation. We examined the influence of age at symptom onset on phenotypic expression.


METHODS
Patients were divided into cohorts according to age of symptom onset. The primary outcome measure was radiological progression (by Bath AS Radiology Index, BASRI). Secondary measures were disease activity (Bath AS Disease Activity Index, BASDAI), function (Bath AS Functional Index, BASFI), numbers undergoing AS related surgery, and percentage with secondary disorders.


RESULTS
Age at onset had no significant effect on radiological progression (young onset vs late onset, 8.0, 8.6, respectively) disease activity (young vs late, 4.4, 4.4), need for non-hip surgical intervention (9%, 8%, respectively), 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 juvenile onset (18%, 8%, respectively; p < 0.001). Regardless of age at onset, spinal progression determined radiologically was greater in those with hip 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 involvement vs non-hip involvement, 10.1 (2.5), 7.1 (3.0), respectively]. Function deteriorates with age (young onset vs late onset, 3.7, 4.5, respectively; p < 0.01).


CONCLUSIONS
(1) Hip disease (young or late onset) is a major prognostic marker for longterm severe disease (patients with hip disease have a spinal score increased by 2.5-3 points or 35-40% more change). (2) Hip involvement is more prevalent among patients with young age at onset. (3) Young onset patients without hip involvement do not have more severe disease. Thus, age at onset, itself, does not influence disease severity. (4) Since hip involvement 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 severity genes. The lack of association between severity and age at onset implies that the determinants of susceptibility and severity are independent.
Brophy
S
S
Epidemiology Department, Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath, UK.
Calin
A
A
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002574:Cervical Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology; D007500:Iritis / Q000453:epidemiology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D015995:Prevalence; D011565:Psoriasis / Q000453:epidemiology; D011859:Radiography; D012446:Sacroiliac Joint / Q000000981:diagnostic imaging / Q000473:pathology*; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*