Comment
The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.
The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.19 Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,20 and psoriasis patients also might consume less whole-grain fiber.21 Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,18 which also has been supported by response to anti-inflammatory medications such as mesalazine.22 Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.
Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al23 found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.
There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.24 Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al25 hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (TH17) pathway,25 which also has been found to play a role in psoriasis pathogenesis.26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.
We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al28 found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.29 Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.
Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.
Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.
Conclusion
Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.