Psoriasis and IBD: Is This Comorbidity for Real?

Psoriasis: Marching Further?

Psoriasis vulgaris is a chronic inflammatory skin disorder associated with systemic comorbidities, including arthritis, cardiovascular disease, renal disease, diabetes mellitus, and metabolic syndrome.^[1] This has led to the concept of the "psoriatic march": psoriasis as a chronic inflammatory condition driving inflammatory disease in multiple organ systems.^[2,3,4] Psoriasis affects up to 10% of adults worldwide, making awareness of comorbidities an important part of patient care. Knowledge of these associations will lead clinicians to establish a pertinent review of systems and order appropriate laboratory tests (eg, fasting blood glucose and lipid profile).

To date, several studies in primarily white populations have suggested an association between psoriasis and inflammatory bowel disease (IBD)—both Crohn disease and ulcerative colitis.^[5,6] Elevated serum and tissue levels of proinflammatory cytokines, including tumor necrosis factor alpha, IL-12, and IL-23, are found in both psoriasis and IBD, and targeted blockade of these cytokines (or cytokine receptors) often yields dramatic improvement in both conditions.^[7,8]

To further explore the strength of any association between psoriasis (vulgaris and arthritis) and IBD, Fu and colleagues^[9] performed a meta-analysis of five case-control or cross-sectional studies (n = 1,826,777) and four cohort studies (n = 5,967,410). Eligible studies were pulled from a larger pool using stringency criteria outlined by the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.

The study findings included the following:

• Meta-analyses of both case-control and cohort studies showed a statistically significant association between psoriasis and IBD.

• Meta-analysis of the five case-control studies showed that patients with psoriasis were 1.7 times more likely to develop Crohn disease and 1.75 times more likely to develop ulcerative colitis than controls. These results were statistically significant.

• Likewise, the cohort studies showed increased odds ratios (psoriasis versus controls) of 2.53 (for Crohn disease) and 1.71 (for ulcerative colitis).

• One "outlier" case-control study from a Taiwanese national database showed a negative association between psoriasis and Crohn disease (odds ratio, 0.70).^[10]

Viewpoint

The link between psoriasis vulgaris, arthritis, and cardiovascular disease is well established, with studies showing that TNF-alpha-blocking therapies (eg, etanercept, adalimumab, infliximab) clear skin plaques, suppress joint inflammation, reduce serum markers of inflammation, and may even slow the progression of cardiovascular disease.^[11] This therapeutic overlap extends to IBD, with many biologics having multiple indications for the treatment of psoriasis vulgaris, psoriatic arthritis, Crohn disease, and ulcerative colitis.

Fu and colleagues presented compelling evidence linking the incidence of psoriasis and IBD. As they speculate, this association may stem from shared genetic abnormalities, immune dysfunction, or even reduced bacterial diversity and pathogenic changes in the gut microbiota.^[12] Intriguingly, all studies with predominantly white participants showed a positive association between psoriasis and IBD, but one study drawn from an Asian population showed an inverse relationship (lower incidence of Crohn disease in patients with psoriasis). Whether this discrepancy reflects a true ethnic difference that can be reproduced remains to be determined.

Do the psoriatic diatheses and IBD share a common pathophysiology, or is the association more tangential? IBD and psoriasis are both characterized by immune dysregulation with tissue-specific (gut, skin, joints) inflammation and damage, but there are obvious clinical, histologic, and therapeutic differences, even between ulcerative colitis and Crohn's disease. Furthermore, monoclonal antibodies targeting IL-17 (ligand or receptor) are highly effective for treating psoriasis but may exacerbate IBD.

Hopefully, growing insight into each condition will shed more light on the others.