SUN-650 - Unexpected Pemphigus Vulgaris after DPP-4 Inhibitor Therapy: When DPP-4 Inhibition Triggers Pemphigus Vulgaris

Introduction
Pemphigus vulgaris (PV) is a rare autoimmune blistering disease affecting the skin and mucous membranes, mediated by autoantibodies against desmogleins. While dipeptidyl peptidase-4 inhibitors (DPP-4i) are well-recognized triggers of bullous pemphigoid, their association with PV is exceedingly rare and up to our knowledge three cases have been reported to date (two associated with sitagliptin and one with linagliptin).

Case Presentation
We report a middle-aged woman with type 2 diabetes mellitus who presented with a four-month history of progressive worsening, widespread blistering involving the skin and mucous membranes. She had been treated with metformin and glibenclamide for five years, with sitagliptin 100 mg once daily added two months prior to symptom onset. No other new medications or vaccinations were introduced. Skin punch biopsy confirmed PV, with direct immunofluorescence demonstrating intercellular IgG and C3 deposition throughout the epidermis.
Sitagliptin was discontinued on admission. The patient was treated with high-dose systemic corticosteroids (prednisolone up to 50 mg daily), complicated by steroid-induced hyperglycemia requiring basal–bolus insulin therapy. Steroid tapering was initiated after clinical stabilization. Adjunctive therapy with cyclosporine and topical tacrolimus was commenced. Secondary skin infection was identified, with wound cultures growing Pseudomonas aeruginosa, and was successfully treated with appropriate intravenous antibiotics.

Outcome
Following cessation of sitagliptin and initiation of immunosuppressive therapy, the patient showed significant clinical improvement, with no new blister formation and resolution of infection. She was discharged after three weeks on a steroid taper with ongoing cyclosporine and topical therapy. Follow-up two weeks post-discharge demonstrated continued clinical improvement.

Conclusion
Although rare, PV should be considered a potential serious adverse effect of DPP-4 inhibitors. Proposed mechanisms include altered desmoglein degradation, cytokine dysregulation, T-helper cells 1 immune impairment, and genetic susceptibility related to HLA-DQB1 alleles. Clinical improvement in our case following drug cessation supports a possible causal relationship. However, further studies are needed to better elucidate the possible mechanisms linking DPP-4 inhibitors to PV.

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