LAUSR

Pembrolizumab-induced reactivation of bullous pemphigoid Dear Editor, Pembrolizumab is a programmed cell death protein 1 (PD1) inhibitor approved for use in several solid carcinomas. It reverses T-cell suppression, causing immune stimulation. Consequently, various immune-related adverse effects are described with its use, with skin toxicity accounting for up to 40% of adverse reactions. Most cutaneous reactions are mild and do not necessitate drug discontinuation. These include morbilliform eruption, vitiligo, and lichenoid dermatitis. However, severe reactions, such as widespread bullous pemphigoid (BP), erythrodermic psoriasis, or toxic epidermal necrolysis, necessitate a change in dose or cessation of PD-1 therapy. BP is the most frequently reported immunobullous disorder associated with pembrolizumab and usually occurs de novo. A 67-year-old man presented with generalized pruritus, gingival erosions, vesicles, and bullae on the face, trunk, and extremities (Fig. 1) after treatment with pembrolizumab for metastatic non-small cell lung adenocarcinoma. Two years prior to this, he was evaluated in the dermatology clinic for similar blisters. At the time, histopathology showed a mild epidermal spongiosis with patchy lymphocytic exocytosis with an upper dermal perivascular lymphocytic infiltrate and numerous eosinophils. Direct immunofluorescence (DIF) revealed a thin wavy linear deposition of C3 and IgG along the basement membrane (Fig. 2). After an inadequate response to topicals, doxycycline, and prednisone (up to 60 mg daily), he achieved clinical remission with rituximab (two 1-gram infusions 2 months apart). Several months later, the patient was diagnosed with metastatic lung adenocarcinoma, and pembrolizumab was initiated. After 12 weeks (four infusions at 3-week intervals) of pembrolizumab, he developed chronic generalized pruritus, followed by urticarial plaques and bullae. Laboratory tests were remarkable for antibodies to BP180 (160 U/mL, ELISA) and eosinophilia (1393 cells/microliter). Because of his morphologic presentation, antiBP180 IgG positivity, and his previous history of BP, a diagnosis of pembrolizumab-induced BP reactivation was rendered. In collaboration with his medical oncologist, pembrolizumab was discontinued and docetaxel was started. Given minimal improvement in his BP with oral prednisone (up to 80 mg daily) and dapsone, another cycle of rituximab (1-gram infusions at 2-week intervals) was administered. His BP achieved remission, but the patient expired from sequelae of his cancer. New-onset BP with PD-1 or PD ligand-1 (PD-L1) inhibitor use is well known; however, few cases highlight reactivation of immunobullous disease previously in clinical remission. The precise pathogenesis of immunotherapy-associated BP is uncertain, and hypotheses include the presence of shared BP180 antigen on tumor cells, in addition to Band T-cell activation and Figure 1 Extensive urticarial plaques with vesicles, bullae, and erosions on the back and bilateral upper limbs