Bullous pemphigoid (BP), the most prevalent autoimmune blistering skin disorder, has been associated with dipeptidyl peptidase-4 inhibitor (DPP4i) treatment in type 2 diabetic patients. This study aimed to investigate the association of DPP4 gene variants, rs3788979 and rs12617656, with classic BP (cBP)- and DPP4i-associated BP predisposition. Fifty-six (56) unrelated patients with cBP, 32 DPP4i-associated BP patients, 60 healthy controls, and 49 diabetic patients receiving DPP4i were included. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Statistical analyses were conducted using SPSS software. For rs3788979, the CT+TT genotypes were significantly associated with increased risk of DPP4i-associated BP compared with cBP [(Odds Ratio (OR) = 2.80, 95% Confidence Interval (CI) = 1.07–7.35; p-value = 0.034] and healthy controls (OR = 0.30, 95% CI = 0.13–0.86; p-value = 0.020). The T allele was also enriched in DPP4i-associated BP (OR = 2.57, 95% CI = 1.09–6.07; p-value = 0.027). Additionally, the TC genotype of rs12617656 (OR = 2.29, 95% CI = 1.04–5.03, p-value = 0.039) showed significant association with cBP susceptibility. These findings highlight DPP4 variants as potential BP risk factors, supporting personalized risk assessment prior to initiating gliptin therapy. Large-scale studies are warranted to validate these associations.

Bullous Pemphigoid (BP) is the most common autoimmune blistering disorder, predominantly affecting elderly patients and often requiring prolonged immunosuppression. Conventional therapies are frequently limited by adverse effects and incomplete disease control, particularly in refractory cases. Increasing understanding of BP pathogenesis has supported the use of targeted biologic therapies; however, evidence regarding combination approaches remains limited. We report two cases of refractory BP treated with combination biologic therapy and provide a focused review of the literature. In the first case, partial response to omalizumab was followed by complete disease control after the addition of dupilumab, allowing successful corticosteroid discontinuation. In the second case, a patient with concomitant psoriasis achieved marked improvement with dupilumab in combination with ongoing IL-17 inhibition (secukinumab), resulting in effective control of both BP and psoriasis. These observations highlight the benefit of simultaneous targeting of complementary inflammatory pathways, including IgE-mediated, Th2, and Th17 axes. Combination biologic therapy may represent a promising strategy in refractory BP, particularly in patients with complex immunologic profiles or coexisting inflammatory diseases.