Metformin/sitagliptin/nivolumab/sitagliptin interaction
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Bullous pemphigoid: 2 case reports. In a report, two men were described, of whom a 74-year-old man developed bullous pemphigoid during concomitant administration of metformin/sitagliptin and nivolumab, and a 75-year-old man developed bullous pemphigoid during concomitant administration of sitagliptin and nivolumab [routes not stated; not all dosages and outcomes stated]. The 74-year-old man (case 1) with type 2 diabetes, had been receiving metformin/sitagliptin since 2011. Additionally, he was receiving amiodarone, enalapril and warfarin concomitantly. He underwent left radical nephrectomy due to clear-cell renal carcinoma in January 2011. In June 2012, a CT scan demonstrated a local recurrence consistent with bone and mediastinal lymph node metastasis. From September 2012 to October 2014, he received sunitinib. In March 2016, he had disease progression, therefore, he was started on nivolumab 240mg every 2 weeks and achieved partial response. In May 2016, he developed dysthyroidism which was treated with thiamazole and then with levothyroxine sodium [levothyroxine] in June 2016. The therapy with nivolumab was maintained. In August 2018, he presented with a rash on the skull and legs and persisting pruritus and tense sero-haematic bullous lesions. Hypereosinophilic syndrome was seen. A skin biopsy revealed an immunoglobulin deposit along the basal membrane with antibodies against C3 and subepidermal blister with eosinophils. The treatment with nivolumab and metformin/sitagliptin was discontinued in September 2018. Subsequently, he was treated with prednisone and betamethasone. Eventually, his bullous pemphigoid lesions improved. Further, prednisone was tapered. Since July 2019, he had stable disease and no skin lesions were seen. Based on these clinical presentation it was concluded that the interaction between metformin/sitagliptin and nivolumab resulted in development of bullous pemphigoid. The 75-year-old man (case 2) with type 2 diabetes, had been receiving treatment with sitagliptin, metformin and gliclazide for >5 years. He also had high BP, treated with atenolol and candesartan cilexetil [candesartan]. In April 2014, he presented with left adrenal gland metastatic relapse of lung adenocarcinoma. From May 2014 to August 2014, he received carboplatin and paclitaxel. In February 2016, due to metastatic progression he was initiated on nivolumab injection 240mg every 2 weeks. In October 2016, after completing 19 injections, he developed tense bullous lesions on the neck, the scalp and the head which suggested bullous pemphigoid. Additionally, he had buccal mucosal polycyclic erosive lesions. Hypereosinophilic syndrome was seen. A skin biopsy of the neck revealed a subepidermal blister with eosinophils. Direct immunofluorescence demonstrated an immunoglobulin deposit along the basal membrane with antibodies against IgG and C3. Serum anti-BPAG2 autoantibodies >199 UA/mL were noted, which confirmed the diagnosis of bullous pemphigoid. He was treated with dapsone, doxycycline and betamethasone. In May 2017, nivo
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