ESA-SRB-AOTA 2019

Linagliptin-associated generalised skin eruption: a case report and review of the literature (#586)

Kay Hau Choy 1 , Avinash Suryawanshi 1 2
  1. Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, NSW, Australia
  2. Sydney Medical School, University of Sydney, Sydney, NSW, Australia

Introduction: Dipeptidyl peptidate-4 inhibitors (DPP4-i) are widely used for treatment of type 2 diabetes mellitus (T2DM) due their favourable tolerability profile; however, severe dermatological side effects have been reported. Herein, we present a rare case of generalised skin eruption in association with linagliptin therapy.

Case: A 54-year-old gentleman with T2DM was started on linagliptin as an add-on therapy to metformin. He also had a background of Susac syndrome for which he received 2-monthly intravenous immunoglobulin. 3 weeks after he was commenced on linagliptin, he developed an intensely pruritic vesicular eruption with no associated bullae on his scalp, trunk and limbs, with prominent involvement of the arms. There was no evidence suggestive of an infectious aetiology. He was treated with topical betamethasone dipropionate and linagliptin was discontinued. His rash and itch subsided over days following linagliptin withdrawal. He was continued on metformin monotherapy for management of his T2DM.

Discussion: DPP4-i increase incretin levels, which decrease glucagon level and stimulate insulin secretion. DPP4 is also present in other body parts including the skin and inhibiting it can have wide-ranging effects beyond those on the pancreas.1 There have been reports of cutaneous adverse effects in association with different types of DPP4-i, albeit uncommon. The time-to-onset of cutaneous drug reactions in these cases range from 1 day to 37 months, with most following the first dose.2,3 Case reports on linagliptin-associated cutaneous reactions are much more limited, with all cases in the form of bullous eruption.1-4 In view of the plausible temporal relationship and the dramatic improvement observed following drug withdrawal, linagliptin was the most probable culprit in the development of cutaneous eruption in our patient. To our knowledge, this case of linagliptin-associated non-bullous skin reaction is the first of its kind. Our case highlights the rare association of severe cutaneous reaction with DPP4i use.

  1. Psomadakis C, Shahzad N, Katz J. Linagliptin-associated blistering and ulceration. BMJ Case Rep. 2017;2017: bcr-2017.
  2. Mendonça FM, Martín-Gutierrez FJ, Ríos-Martín JJ, Camacho-Martinez F. Three cases of bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors-one due to linagliptin. Dermatology. 2016;232: 249-53.
  3. Nakatani K, Kurose T, Hyo T, Watanabe K, Yabe D, Kawamoto T, et al. Drug-induced generalized skin eruption in a diabetes mellitus patient receiving a dipeptidyl peptidase-4 inhibitor plus metformin. Diabetes Ther. 2012;3: 14.