Psoriasis Comorbidities: Making the Connection

For many years, it has been known that psoriasis patients are prone to a variety of comorbities, including increased cardiovascular disease risk, a risk that has gotten a significant amount of attention in recent publications.  A similar association between psoriasis and diabetes mellitus has been reported in numerous publications.¹  There is also a likely association with the severity of psoriasis and prevalence of diabetes.²  Additionally, in some studies, it appears that some common anti-psoriatic drugs, namely methotrexate and systemic corticosteroids, may be associated with increased odds of psoriasis patients developing diabetes.¹

As often happens, it is not clear at this point whether these associations are causal, or merely correlative.  However a recent study on the seasonality of diabetes in the general population of the Netherlands shows an increase in first diagnosis in the autumn/winter,4 much like we see in psoriasis and other autoimmune conditions.  Typically, seasonality is generally associated with solar effects (ultraviolet exposure, vitamin D levels, melatonin levels) and with increased rates of viral disease in the winter months (rotavirus, Epstein-Barr, etc.).

Current diabetic mouse model research into vitamin D receptor activity seems to indicate a role for low vitamin D levels in contributing to blood glucose control issues.5  There are several ongoing and completed trials, as yet unpublished, concerning vitamin D supplementation in pre-diabetic and diabetic patients which may have results that are pertinent to the dermatology community.

There has also been research in the orthopedic community in correlating vitamin D levels as a drug side effect, with a recent publication linking methotrexate with decreased vitamin D levels.  As can be expected, many of the patients involved in those studies, were taking methotrexate as part of their arthritis therapy, and were not separated to specifically analyze those with psoriatic arthritis.  Although further research is needed on the topic, it seems reasonable that the increased diabetes mellitus risk in psoriasis patients treated with methotrexate might well relate to vitamin D levels.  This may lead to both vitamin D supplementation in patients on methotrexate, as well driving prescribing choices away from methotrexate to competing therapies that are not vitamin D depleting, especially in patients with other risk factors for diabetes.

(1) Lee, Lin , Lai. Increased risk of diabetes mellitus in relation to the severity of psoriasis, concomitant medication, and comorbidity: a nationwide population-based cohort studyJ Am Acad Dermatol. 2014 Apr;70(4):691-8. doi: 10.1016/j.jaad.2013.11.023. Epub 2014 Jan 9.

(2) Armstrong , Harskamp CT, Armstrong EJ. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis.JAMA Dermatol. 2013
Jan;149(1):84-91. doi: 10.1001/2013.jamadermatol.406.

(3)Spaans EA, van Dijk PR, Groenier KH, Brand PL, Reeser MH, Bilo HJ, Kleefstra N. Seasonality of diagnosis of type 1 diabetes mellitus in the Netherlands (Young Dudes-2).J Pediatr Endocrinol Metab. 2016 Jun 1;29(6):657-61. doi: 10.1515/jpem-2015-0435.

(4)Watad, Azrielant, Bragazzi, Sharif, David, Katz, Aljadeff, Quaresma, Tanay , Adawi, Amital , Shoenfeld Seasonality and autoimmune diseases: The contribution of the four seasons to the mosaic of autoimmunity.Autoimmun. 2017 Aug;82:13-30. doi: 10.1016/j.jaut.2017.06.001. Epub 2017 Jun 16.

(5)Neelankal John, Iqbal, Colley, Morahan, Makishima, Jiang.Vitamin D receptor-targeted treatment to prevent pathological dedifferentiation of pancreatic β cells under hyperglycaemic stress.Diabetes Metab. 2017 Sep 11. pii: S1262-3636(17)30479-2. doi: 10.1016/j.diabet.2017.07.006. [Epub ahead of print]