Abstract:

Treatment with anti-PD-1 antibodies has become the standard of care for many advanced carcinomas, and has changed the life expectancy of patients with metastatic disease. However, is not without significant adverse effects. Important cutaneous effects include lichenoid reactions, SJS/TEN and bullous pemphigoid (BP). We report a 93 year old man with castration resistant metastatic prostate cancer on pembrolizumab who presented with bilateral leg pain. He had marked bipedal edema and a single tense bulla felt to be secondary to fluid overload. After developing vesicles on the opposite dorsal foot, biopsies were obtained revealing a subepidermal vesicle, a superficial perivascular and interstitial infiltrate of lymphocytes and eosinophils, and linear deposition of IgG and C3 at the dermoepidermal junction on direct immunofluorescence, consistent with BP. Drug induced BP can be caused by over 90 medications, including cancer immunotherapy, analgesics, antihypertensives, antibiotics, diuretics, gliptins and biologics. Of these, pembrolizumab is among the most common, although it remains a rare adverse event. The clinical, histopathologic and immunologic features are similar to classic BP. However, the latency of anti-PD-1 associated bullous eruptions is longer compared to other cutaneous toxicities, with onset ranging from 3 to 84 weeks. Our patient presented with leg pain and edema, and the diagnosis of BP was delayed because it was not suspected clinically. Treatment of anti-PD-1 induced bullous pemphigoid includes systemic steroids and steroid sparing agents. In some patients the drug needs to discontinued, however, despite this, lesions can persist and new blistering may occur. Our patient’s pembrolizumab was discontinued and prednisone initiated with rapid improvement. We present this case to increase awareness of drug induced BP. Onset of vesicles may not be temporally related to the causative medication, and the diagnosis can thus be delayed and easily overlooked.

Financial Disclosure:
No current or relevant financial relationships exist.

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Marian Caligayahan, MD