Bullous pemphigoid induced by vildagliptin: a report of three cases

Abstract

To report three cases of bullous pemphigoid in patients treated with vildagliptin. Case 1: An 86-year-old woman presented with bullous pemphigoid after 1 month of treatment with vildagliptin and metformin. After introduction of clobetasol, the symptoms resolved although vildagliptin was continued. However, the skin lesions reappeared 3 months later. Sustained remission was achieved only after definitive withdrawal of vildagliptin. Case 2: A 79-year-old man presented with bullous pemphigoid after 37-month treatment with gliclazide, vildagliptin and metformin. The disease at first responded to clobetasol but 3 months later the lesions reappeared. They finally regressed when the gliptin was discontinued. Case 3: A 77-year-old woman, treated with gliclazide and vildagliptin for 26 months, presented with bullous pemphigoid, which responded well to discontinuation of the gliptin and topical clobetasol. Gliptins are new molecules for treatment of type 2 diabetes mellitus, which have been suspected of implication in bullous pemphigoid. Such cases have been described in the literature (seven with vildagliptin and three with sitagliptin). In nine of these cases, the gliptin was associated with metformin, but the latter had never been considered responsible. The mechanism implicated in the development of bullous pemphigoid has not yet been clearly identified, but may involve a modified immune response or alteration of the antigenic properties of the epidermal basement membrane. These reports support the risk of bullous pemphigoid in patients exposed to gliptins.

Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study in the French Pharmacovigilance Database

“…The high ROR found with vildagliptin suggests a higher risk with this gliptin compared with the others, while it was marketed in the same year as sitagliptin in France. Vildagliptin has been involved in 10 of the 16 cases described to date in the literature . It is interesting to specify that sitagliptin (and not vildagliptin) is the most prescribed gliptin in France, as well as in the rest of Europe .…”

“…However, cutaneous adverse drug reactions (ADRs) have been described for DPP‐IV inhibitors, particularly anaphylactic reactions, drug reaction with eosinophilia and systemic symptoms and Stevens–Johnson syndrome . Some case reports have also described bullous pemphigoid under DPP‐IV inhibitors; however, comparative studies assessing the link between exposure to DPP‐IV inhibitors and bullous pemphigoid have not been reported.…”

Three Cases of Bullous Pemphigoid Associated with Dipeptidyl Peptidase-4 Inhibitors - One due to Linagliptin

“…These lesions were not biopsied then, and they did not relapse in subsequent episodes. Only 14 cases of DPP-4 inhibitor-associated BP have been described (table 1), 10 of which were due to the association between vildagliptin and another antidiabetic, most frequently metformin [5,7,8,10]. Metformin has been widely used for the treatment of diabetes, and there are no described cases of BP due to metformin.…”

Diabetes medications: Impact on inflammation and wound healing

“…As for adverse effects, DPP-4i and GLP-1 receptor agonists have been associated with pancreatitis and pancreatic cancer although several studies have indicated no increased risk including a recent meta-analysis (Li, Shen et al 2014). Also, vildagliptin has been recently associated with skin reactions although the reported instances are very rare (7 cases in total) and most patients were on metformin as well (Bene, Jacobsoone et al 2015) making a clear inference difficult. In summary, as the most recent diabetes medication class to show anti-inflammatory potential, further research is needed to determine whether DPP-4i can be used to promote wound healing.…”