engleski

A case of severe bullous pemphigoid associated with the use of dipeptidyl peptidase-4 inhibitor sitagliptin

We are presenting a case of a patient diagnosed with bullous pemphigoid (BP), occurring as a rare side effect of the commonly used antidiabetic drug sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4i). The first reported case of BP associated with DPP4i was recorded back in 2011. Since then, evidence continued to grow, including this case report as it follows. A 52-year-old female patient was admitted due to the generalized appearance of densely disseminated vesicles and bullae on erythematous urticarial plaques accompanied by severe itching. She also had multiple erosions on the oral mucosa and reported recent onset of hoarseness. The skin rash progressed over the course of previous two months and failed to improve upon treatment with corticosteroid creams. Patient’s previous medical history was significant for type 2 diabetes mellitus which was controlled with gliclazide, metformin/sitagliptin and insulin glargine. The patient was diagnosed with BP based on the clinical presentation, histopathological analysis of the lesional skin and findings of the linear deposits of immunoglobulins IgG and C3 along the basement membrane in the direct immunofluorescent examination of the perilesional skin. Due to generalized presentation of the skin rash, the patient was put on high dose of prednisone. Since the skin rash failed to improve within the following two weeks, and the patient’s glycemia severely worsened despite of intensified insulin therapy, azathioprine was also introduced. As a complication of the affection of oral mucosa and obstruction of the parotid excretory duct, the patient developed acute sialadenitis, which was treated with massages and antibiotics. After excluding the paraneoplastic aetiology, we suspected the severe presentation of the disease to be associated with the use of sitagliptin, a DPP4i antidiabetic which was therefore discontinued. This finally resulted in stabilisation of the skin disease within the following 2 weeks and remission within the next month. However, the course was further complicated with the onset of acute toxic hepatitis associated with the increase of azathioprine dose from 150 mg/day to 200 mg/day and characterized by significant alteration of the liver tests (AST 193, ALT 243, ALP 291, GGT 1625, LDH 412). Azathioprine was promptly discontinued, with liver function tests returning to normal values in the following 2 weeks. Interestingly, the skin disease remained in remission without introduction of any new immunosuppressants. Finally, there was no relapse of the disease even after subsequent gradual prednisone taper from 60 mg/day to 10 mg/day, which further suggests that the disease was induced by the incriminated drug sitagliptin. DPP4i are oral antidiabetics that increase incretin levels and therefore cause an increase in insulin secretion, decrease glucagon secretion and are improving glycemic control. DPP4i can be used as monotherapy in diabetes, in combination with insulin, or most commonly with metformin. The average time from ingestion of the drug to the onset of BP symptoms varies according to various studies from 5 months to 6 years. Such a long latency period indicates the importance of taking detailed patient history and consideration of not so recently introduced therapy a s a possible cause of the skin disease.

Bullous pemphigoid ; sitagliptin

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