Case Presentation: Immunotherapy is an emerging therapeutic option in the field of oncology. Dermatological toxicities are the most prevalent immune-related adverse events associated with immunotherapy. Herein, we report a case of a 60-year-old male who developed localized bullous pemphigoid after nearly a year of treatment with a PD-1 inhibitor, nivolumab, for metastatic renal cell carcinoma. Nivolumab is a monoclonal antibody against immune checkpoint inhibitor programmed cell death protein-1.We present a 60-year-old male with metastatic clear cell renal carcinoma who presented for evaluation of pruritic, painful blisters on scrotum for the past 6 months. Past medical history was notable for nephrectomy, radiation, and immunotherapy with pazopanib, ipilimumab, and nivolumab. He had received immunotherapy for nine months prior to presentation. On examination, there were lichenified plaques with focal erosions and intact vesicles on the right anterior scrotum extending to the base of the penis. There was no other skin surface involvement. Three punch biopsies of the affected area showed subepidermal split with eosinophils, neutrophils, and plasma cells. Direct immunofluorescence (DIF) showed linear IgG and patchy linear IgA deposition at the basement membrane. Enzyme-linked immunosorbent assay (ELISA) results of the biopsy specimen demonstrated an increased IgG BP 180 antibody level. The clinical and histological features were consistent with drug-induced bullous pemphigoid. The patient was initially treated witha topical triamcinolone 0.1% ointment with minimal improvement. After receiving the biopsy results, his immunotherapy was held, and he was started on clobetasol 0.05% ointment, oral doxycycline 100 mg, and niacinamide 200 mg twice daily. However, his lesions progressed, and he was subsequently started on prednisone 20 mg daily, in addition to topical clobetasol cream twice daily, which ultimately resulted in improvement of lesions.
Discussion: Immunotherapies have ushered in a new era of treatment options for multiple malignancies. It has transformed the field of oncology, and new agents are emerging as we further understand the tumor immunity. Immune checkpoint inhibitors targeting the PD-1 pathway are commonly used and have shown significant antitumor activity against solid and hematological malignancies. PD-1 biological pathways play a significant role in activating apoptosis in cells, and PD-1 inhibitors also block the inhibitory signals on T cells. Indiscriminate immune functioning is the basis of immunotherapy related adverse events (irAEs) and upto 40% of anti-PD-1 therapy induced skin toxicty has been reported. We report a case of a PD-1 inhibitor-induced localized bullous pemphigoid. Bullous pemphigoid is a rare but serious dermatological toxicity associated with checkpoint inhibitors. Pruritus is a hallmark symptom of the prodromal phase of BP, and blisters and rash develop later in the course of the disease. Diagnosis can be confirmed with direct immunofluorescence on skin biopsy. Treatment includes topical and oral corticosteroids. Doxycycline and niacinamide can be considered as an adjunct therapy.
Conclusions: Immunotherapy is routinely used in cancer management, and this case highlights the importance of clinician’s awareness of cutaneous immune-related adverse events. Careful evaluations of any skin findings are vital with a low threshold for referral to dermatology for a skin biopsy.