(Last Updated On: March 15, 2021)

Gwendolyn Y. Wong, MD, FPDS, Mary Joyce W. Chiong, MD

ABSTRACT

Introduction: Bullous pemphigoid (BP) is a chronic, autoimmune blistering disease occurring primarily in the elderly population. The pathogenesis of this condition has been strongly linked to the presence of circulating and tissue-bound autoantibodies against the basement membrane antigens BP180 and BP230. In most cases, the causative agent remains unidentified, but in a selected few, certain medications have been implicated in the pathogenesis of the disease. Dipeptidyl peptidase-4 inhibitors (-gliptins), in particular, which are used primarily in the treatment of diabetes mellitus, have been increasingly suspected to be a prime aggravating drug in the incidence of BP.

Case summary: Bullous pemphigoid (BP) is a chronic autoimmune blistering disease mainly affecting the elderly population. While the pathogenesis has not yet been fully elucidated, it has been suggested that there is a correlation observed with certain groups of medications. Among drugs correlated with bullous pemphigoid, the group of dipeptidyl peptidase-4 inhibitors (-gliptins) used in the treatment of diabetes mellitus has been one of the most strongly associated. This is a case of a 64-year-old female on regular maintenance medications including linagliptin who developed generalized pruritus followed a week after by appearance of localized fluid-filled vesicles and bullae on the right lower leg. BP associated with dipeptidyl peptidase-4 inhibitors is characterized as “non-inflammatory” – lesions are localized and associated with less erythema compared to the classic presentation. Serum eosinophilia was absent, and serum autoantibody against BP180 was positive. Histopathologic and immunohistologic results revealed characteristics similar to classic bullous pemphigoid. The association of dipeptidyl peptidase-4 inhibitors to the development of BP was observed to have a long latency period between initiation of drug to onset of lesions. There was significant improvement after both withdrawal of the drug and standard steroids and doxycycline. Unlike other drug-induced BP, dipeptidyl peptidase-4 inhibitor-associated BP was found to have similar prognosis with the classic manifestation as the patient noted recurrence one month after remission despite withdrawal of inciting drug.

Conclusion: There has been increasing incidence in DPP-4 inhibitor-associated BP. Though its clinical course is similar to classic BP, a non-inflammatory and more localized presentation would prompt suspicion of association with drug. The long latency in DPP-4 inhibitor and lesion onset suggests that rather than being simply an adverse reaction to treatment, DPP-4 inhibitor-associated BP should be viewed as a drug-associated or drug-aggravated disease. Determining the association of BP to DPP4-inhibitors is significant as the management for these patients not only entails standard management of BP but also withdrawal of the suspect drug, which in this case was found to significantly improve the patient’s lesions after one month. Unlike other drug-induced BP, however, DPP-4 inhibitor associated BP was found to have the same prognosis with classic BP as the patient noted recurrence one month after remission.

Keywords: DPP-4 inhibitor-associated bullous pemphigoid, drug-associated bullous pemphigoid, dipeptidyl peptidase-4 inhibitor, bullous pemphigoid, gliptins

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