Bullous Pemphigoid Risk in Patients With Diabetes Treated With DPP-4 Inhibitors

Bullous pemphigoid blisters
Bullous pemphigoid blisters
The association between DPP-4 inhibitor use and the risk for developing bullous pemphigoid was examined.

The use of dipeptidyl-peptidase 4 (DPP-4) inhibitors is associated with an increased risk for bullous pemphigoid among patients with diabetes, according to a study published in JAMA Dermatology.

The investigators sought to analyze the risk for bullous pemphigoid among different DPP-4 inhibitor agents and to gather data on the clinical features and prognostic outcomes of these patients. In addition, the study also compared patients with diabetes who developed DPP-4 inhibitor-associated bullous pemphigoid against patients with diabetes and bullous pemphigus who did not receive DPP-4 inhibitors as part of their treatment.

Eighty-two patients with diabetes and bullous pemphigoid were compared with 328 control participants without bullous pemphigoid. The control group was matched to cases by age, sex, and year of diagnosis. DPP-4 inhibitor exposure was determined by review of medical records. The severity of disease was categorized by clinical presentation and placed cases either in a mild to moderate or severe group. Hematological data was also collected from the initial admissions of patients with new onset bullous pemphigoid.

A significant association was observed between DPP-4 inhibitor intake and the development of bullous pemphigoid (odds ratio [OR] 2.83; 95% CI, 1.70-4.71). The strongest association was seen with the use of vildagliptin (OR 9.28; 95% CI 4.54-18.99), followed by linagliptin (OR 6.61; 95% CI, 2.28-19.17). There was no association was found between bullous pemphigoid and treatment with sitagliptin. Concomitant treatment with metformin did not have an effect on risk for bullous pemphigoid.

Upon comparison, patients with DPP-4 inhibitor exposure had a greater rate of mucosal involvement than patients who did not take a DPP-4 inhibitor. The severity of disease was similar between the 2 groups. The most significant hematological findings were that patients with bullous pemphigoid who did not use DPP-4 inhibitors had higher circulating eosinophil counts and a greater prevalence of peripheral eosinophilia.

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Patients with bullous pemphigoid who discontinued treatment with DPP-4 inhibitors experienced varying degrees of remission compared to less favorable clinical outcomes for patients who did not discontinue treatment with DPP-4 inhibiting agents.

Study limitations include small sample sizes, the retrospective nature of the data, and the fact that the study was carried out in a tertiary referral setting, which can cause selection bias.

Overall, DPP-4 inhibitor usage was found to increase the risk for bullous pemphigoid, with a higher risk associated with the use of either vildagliptin or linagliptin. Resarchers suggest recommending discontinuation of treatment with DPP-4 inhibitors in patients with diabetes once the diagnosis of bullous pemphigoid is made.


Kridin K, Bergman R. Association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors in patients with diabetes [published online August 8, 2018]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.2352