Importance: Antagonist antibodies to programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have shown remarkable activity in multiple tumor types. Recent US Food and Drug Administration approval of such agents for advanced melanoma, non-small cell lung cancer, and renal cell carcinoma has hastened the need to better characterize their unique toxicity profiles.Objective: To provide a clinical and pathologic description of the lichenoid mucocutaneous adverse effects seen in patients receiving anti-PD-1/PD-L1 treatment.Design, Setting, and Participants: Patients with advanced cancer who were referred to dermatology at Yale-New Haven Hospital, a tertiary care hospital, after developing cutaneous adverse effects while receiving an anti-PD-1 or PD-L1 antibody therapy either as monotherapy or in combination with another agent were identified. Medical records from 2010 to 2015 and available skin biopsy specimens were retrospectively reviewed.

Background-There is increasing recognition of distinct inflammatory eruptions associated with checkpoint inhibitors. A better understanding of their severity, therapeutic response and impact on cancer treatment is needed.Objective-To analyze the different rashes associated with immunotherapy referred to our institution's oncodermatology clinic and inpatient consultative service, and to evaluate their therapeutic response and impact on immunotherapy.Methods-We retrospectively reviewed patients' medical records referred to the oncodermatology clinic or inpatient dermatology service between 2016-2018 at Yale-New Haven Hospital for eruptions that developed during immunotherapy.Results-98 patients (51 men, 47 women) treated with checkpoint inhibitors developed 103 inflammatory eruptions, with a range of mean latency of 0.2-17.7 months. A minority (25/103; 24.3%) required immunotherapy interruption, most notably immunobullous (7/8; 87.5%), lichenoid (8/26; 30.8%), maculopapular (6/18; 33.3%), and SJS-like (2/2, 100%) reactions. Only 3/16 (18.8%) interrupted cases developed a grade 2 or 3 flare on rechallenge. Most reactions (93/103; 90.3%) responded to dermatologic therapy and/or immunotherapy interruption.

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Background: Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy.Objective: On the basis of preventing the accumulation of toxic metabolites while replenishing essential end-products, we studied the efficacy of topical lovastatin/cholesterol in different variants of porokeratosis.Methods: A series of 5 patients with disseminated superficial actinic porokeratosis (DSAP,n=1), porokeratosis palmaris et plantaris disseminata (PPPD,n=2) and linear porokeratosis (LP,n=2) were enrolled. Patients were genotyped prior to initiation of therapy and then applied topical lovastatin/cholesterol twice daily to a unilateral defined treatment area for up to 3 months. Response was evaluated and patients were photographed every visit.Results: Three patients had MVD mutations and 2 patients had PMVK mutations. Treatment with topical lovastatin/cholesterol (but not cholesterol alone) resulted in near complete clearance of DSAP lesions after 4 weeks of therapy, and moderate improvement of lesions in PPPD and LP. There were no adverse events.Limitations: Case series design with a small number of patients. Conclusion:Topical cholesterol/lovastatin is a safe and effective therapy for porokeratosis that underscores the utility of a pathogenesis-based therapies which replace deficient end-products and prevent accumulation of potentially toxic precursors.

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