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

OBJECTIVE: To explore the nature of the interrelationship between inflammatory disease of the spine/joints, skin, eye, and bowel [i.e., ankylosing spondylitis (AS), psoriasis, iritis, inflammatory bowel disease (IBD)].

METHODS: The study used 4 approaches: (1) analysis of the prevalence of secondary disorders within the AS individual (chi-square and matched pair analysis); (2) study of the temporal relationship between the onset of the different conditions; (3) evaluation of the prevalence of disease among first degree relatives; and (4) influence of secondary disorders on outcome of AS.

RESULTS: 1. Among 3287 patients with AS, more than expected had either spondylitis associated with multiple co-disorders or pure AS (with no co-diseases); 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 controls. 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 predict the highest prevalence of co-diseases (i.e., psoriasis, IBD, iritis, or AS) within family members, followed by those AS patients with only IBD, psoriasis, or iritis in descending order. 4. Both psoriasis and IBD increase severity in terrms of function and disease activity of AS in the patient. Radiological 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 susceptibility genes of these co-disorders appear to overlap with each other and with AS: 1. A patient with 2 inflammatory conditions is at an increased risk of developing an additional related inflammatory disorder. 2. Those with enteropathic spondylarthritis would appear to carry the greatest genetic load in terms of first degree relatives developing inflammatory conditions (including psoriasis and iritis that are not seen in the index IBD-AS patient). 3. The secondary disorders do not precede AS (arguing against psoriasis and IBD allowing for an environmental conduit to pathogenic triggers in 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.