Sitagliptin Induced Bullous Pemphigoid - A Rare Case Report

Bullous pemphigoid is an uncommon autoimmune skin condition that typically presents with large, fluid-filled blisters and itchy, hive-like rashes. In some cases, it can be triggered by medications. Bullous pemphigoid is an acquired autoimmune blistering disorder that affects the area just beneath the outer layer of the skin. It is sometimes associated with the use of certain medications, including Sitagliptin. Sitagliptin is an oral antidiabetic medication that belongs to the class of DPP-4 inhibitors. It helps lower blood glucose levels by enhancing the release of gut hormones like GLP-1 and GIP after meals, which stimulate insulin secretion in a glucose-dependent manner and suppress glucagon release.^[1] Patients with bullous pemphigoid (BP) typically have circulating autoantibodies against BP180 and BP230, which are key components of the hemidesmosomes that help anchor basal keratinocytes to the underlying skin layers. The DPP-4 protein, also known as CD26, is found in various cell types, including T-lymphocytes, and plays a role in immune regulation.^[2] The exact mechanism behind bullous pemphigoid associated with DPP-4 inhibitors remains unclear. However, it is suggested that inhibition of CD26 (a form of DPP-4) on T-cells may influence immune system activity in a way that contributes to the development of the condition.^[3] Over 17-months (from December 2018 to May 2020), five male patients with stage 3b to 5 chronic kidney disease (CKD) were diagnosed with bullous pemphigoid associated with DPP-4 inhibitor. Skin biopsies were performed in all cases to confirm the diagnosis. Among these patients, three had been receiving vildagliptin and two were on linagliptin. Management in all cases involved the permanent discontinuation of the suspected DPP-4 inhibitor and initiation of corticosteroid therapy.

CASE PRESENTATION:

A 67-year-old male presented to the adult emergency department at Aster CMI Hospital, Bengaluru, with complaints of generalized weakness and excessive drowsiness persisting for the past month. Clinical examination revealed multiple blisters over the trunk, face, and scalp, as well as on both palms and soles. These lesions appeared as erythematous plaques with crusted erosions.

The patient had recently undergone evaluation at an outside facility, where significantly elevated blood glucose levels were detected. There prescribed combination of OHAs (Sitagliptin, metformin and dapagliflozin). Table-1, reaction started on day of 15^th, Patient revealed that Initially it’s seen in palm and soles. Image-1 and later it came on back. Image-1. But he had no prior history of diabetes mellitus or hypertension, he had been started on sitagliptin based on these elevated readings.

TABLE-1: MEDICINE WITH DOSAGE, FREQUENCY AND DURATION

IMAGE-1: BLISTERS OBSERVED ON THE PALM AND SOLES

IMAGE-1: BLISTERS OBSERVED ON THE BACK

On further assessment at our center, his random blood sugar was 242 mg/dL and HbA1c was 10.5%, confirming poorly controlled diabetes. For investigations, skin biopsy TABLE-3, Direct immunofluorescence TABLE-2 sample specimen taken from Lesional bulla and perilesional – reports favoring bullous pemphigoid. Other routine labs, were conducted. Based on the clinical presentation and diagnostic findings, a multidisciplinary team comprising internal medicine and dermatology departments diagnosed the patient with uncontrolled type 2 diabetes mellitus, urinary tract infection (UTI), acute kidney injury (AKI) and bullous pemphigoid.

Based on the patient’s clinical findings, examination results, and skin biopsy, the medical team decided to discontinue sitagliptin, considering its potential link to bullous pemphigoid. The use of SGLT-2 inhibitors was also avoided in view of the ongoing urinary tract infection, and the entire class of DPP-4 inhibitors was withheld to prevent recurrence or worsening of skin symptoms. The patient was initiated on Inj. NOVORAPID for glycemic control. His treatment regimen also included Tab. BILASTINE 20 mg, Tab. COLCHICINE 0.5 mg, TAB. WYSOLONE 20 mg and FUSIDIC ACID cream for local application. STAT intramuscular dose of Inj. TRICORT 40 mg, Patient recovered after being treated. Image-1

TABLE -2:

DIRECT IMMUNOFLUORESCENSE: The report shows positive IgG, IgM and C3 linear deposition along the basement membrane and IgM is negative

TABLE-3:

HISTOLOGICAL FINDINGS:

Fig.2. Lesional bulla,Perilesional area:- Features are of immune mediated vesiculo-bullous disease, with subepidermal bulla and linear deposits of IgG and C3 (along basement membrane), favouring Bullous pemphigoid

IMAGE-2: RECOVERY NOTED IN PALM AND SOLES