Inflammatory eye, skin, and bowel disease in spondyloarthritis: Genetic, phenotypic, and environmental factors

Objective. To explore the nature of the interrelationship between inflammat ory disease of the spine/joints, skin, eye, and bowel [i.e., ankylosing spo ndylitis (AS), psoriasis, iritis, inflammatory bowel disease (IBD)]. Methods. The study used 4 approaches: (1) analysis of the prevalence of sec ondary disorders within the AS individual (chi-square and matched pair anal ysis); (2) study of the temporal relationship between the onset of the diff erent conditions; (3) evaluation of the prevalence of disease among first d egree relatives; and (4) influence of secondary disorders on outcome of AS. Results. 1. Among 3287 patients with AS, more than expected had either spon dylitis associated with multiple co-disorders or pure AS (with no co-diseas es); fewer than expected had AS plus a single co-disease (chi-square = 32.2 , p < 0.001). In a matched pair analysis, patients with AS and a secondary disorder were more likely to have an additional concomitant disease, e.g., IBD-AS (n = 335) patients had a higher prevalence of iritis [45.4% vs 36.7% ; OR 1.4 (1.1-2.0)] or psoriasis [23.9% vs 14.3%; OR 1.9 (1.3-2.8)] than co ntrols. 2. Among our database subjects, the symptomatic onset of the spinal disease precedes or is contemporaneous with gut, skin, and eye involvement (matched pair t test, p < 0.001). 3. Patients with multiple disorders pred ict the highest prevalence of co-diseases (i.e., psoriasis, IBD, iritis, or AS) within family members, followed by those AS patients with only IBD, ps oriasis, or iritis in descending order. 4. Both psoriasis and IBD increase severity in terms of function and disease activity of AS in the patient. Ra diological change is greatest for those AS subjects with iritis. Conclusion. There is a striking overlap within patients and family members of rheumatological, dermatological, and gastroenterological diseases. The s usceptibility genes of these co-disorders appear to overlap with each other and with AS: 1. A patient with 2 inflammatory conditions is at an increase d risk of developing an additional related inflammatory disorder. 2. Those with enteropathic spondylarthritis would appear to carry the greatest genet ic load in terms of first degree relatives developing inflammatory conditio ns (including psoriasis and iritis that are not seen in the index IBD-AS pa tient). 3. The secondary disorders do not precede AS (arguing against psori asis and IBD allowing for an environmental conduit to pathogenic triggers i n AS). The susceptibility factors for these inflammatory conditions may be additive or have a synergistic effect on each other. There is evidence for a shared gene hypothesis.