Celiac Disease May Increase the Risk of Developing Psoriasis

Patients with celiac disease (CD) have an increased risk of developing psoriasis, whereas psoriasis was not found to affect the risk of developing CD, according to a study published in Scientific Reports.

The study authors noted that the pathological mechanism of psoriasis is complex and unclear, however, it’s accepted that psoriasis impacts the dysregulation of the innate and adaptive components of the immune system. CD, which is also an autoimmune disease, is similarly characterized by a specific serological and histological profile that is triggered by the consumption of gluten in genetically predisposed individuals.

Because psoriasis and CD are both linked to multiple autoimmune disorders, prior observational studies have sought to establish an association between psoriasis and CD, which produced inconsistent results.

“Moreover, a comprehensive meta-analysis has found that psoriasis patients were 2.16-fold more likely to be diagnosed with CD, and the CD patients were 1.8-fold more likely to have psoriasis,” the study authors wrote. “However, limitations should be acknowledged in observational studies, for example, it was difficult to control confounding factors, such as environmental factors, education levels, socio-economic status, et al. Moreover, it was unable to fully understand the true causal effect in observational studies because there might be a reverse causal effect.”

The investigators noted that CD and psoriasis are both T-cell-mediated immune diseases, with immunogenic mechanisms that may explain the causal link between both conditions. In CD, gliadin-derived peptides activate lamina propria effector CD4 + T cells. This action may cause cytokines to be released and activate downstream effector T cells.

Patients with CD have been found to have altered intestinal barrier dysfunction. As such, the study authors noted that proinflammatory cytokines and activated T cells may enter the blood with a subsequent increase in the dermis and epidermis, which may lead to the development of psoriasis.

To address the inconsistent findings of prior research efforts, the study authors used a bidirectional 2-sample Mendelian randomization (MR) study. They evaluated the genetic relationship between psoriasis and CD with an unbiased MR design.

The investigators extracted eligible instrument variables with genome-wide significance (p < 5E−08) of summary-level datasets from genome-wide association studies among the European population. The analyses showed that genetically doubling the odds of CD elevated the risk for psoriasis (p = 1.58e−03, OR [95% CI] 1.232 [1.061–1.432]), which was supported by sensitivity analyses. However, genetically determined psoriasis was not found to be associated with the risk for CD (IVW: p = 0.985, OR [95% CI] 1.000 [0.965–1.037]).

Notably, the study authors said that the gluten-free diets of patients with CD may be responsible for the elevated risk of psoriasis in patients with CD. They noted that gluten-free diets may cause deficiencies in several vitamins and nutrients, such as vitamins D and B12, as well as iron, calcium, and folate, which could lead to the development of psoriasis. They added that a gluten-free diet may produce higher content of both saturated and hydrogenated fatty acids.

“Saturated fatty acids could sensitize myeloid cells to an increased inflammatory response in answer to proinflammatory stimuli, which in turn augments the activation of keratinocytes and exacerbates psoriasis,” the study authors wrote. “In general, gluten-free diet plays an important role in the causality of CD on psoriasis.”

The investigators concluded that the study presents novel genetic evidence that patients with CD have an elevated risk of developing psoriasis, while psoriasis is not associated with the risk for CD.

“Clinicians should be aware of the associations and pay attention to skin manifestations in patients with CD,” the study authors wrote.

Reference

Li, L., Fu, L., Zhang, L. et al. Mendelian randomization study of the genetic interaction between psoriasis and celiac disease. Sci Rep 12, 21508 (2022). https://doi.org/10.1038/s41598-022-25217-y. Published December 13, 2022. Accessed December 14, 2022.