Eruptive Melanocytic Nevi in the Setting of Encorafenib, Cetuximab, and Binimetinib Combination Therapy: A Case Report.

Introduction: The development of new and changing melanocytic lesions has been increasingly reported as an adverse dermatologic toxicity of BRAF inhibitor therapy. Melanocytic lesions and melanomas induced by BRAF inhibitor therapy that lack BRAF V600E expression have been less commonly described. One mechanism that has been proposed for the development of BRAF inhibitor-induced melanocytic lesions, including those lacking BRAF V600E expression, is the paradoxical activation of the MAPK signaling pathway in BRAF wild-type (BRAFWT) cells. Case Presentation: Herein, we report a rare case of a 39-year-old woman who developed numerous BRAF V600E-negative eruptive melanocytic nevi following encorafenib, cetuximab, and binimetinib combination therapy, the current standard of care for the treatment of BRAF-mutant metastatic colorectal cancer. Conclusion: Patients treated with BRAF inhibitors, with or without related combination therapies, who develop BRAFWT melanocytic lesions are at risk for developing both dysplastic nevi and melanoma, thereby warranting baseline dermatoscopic evaluation prior to the initiation of therapy as well as regular follow-up during and after treatment.

Acne excoriée: Diagnostic overview and management.

Acne excoriée (AE) is a skin picking disorder (SPD) within the group of obsessive compulsive (OCD) and related disorders characterized by the compulsive manipulation of acne lesions. AE typically appears in females during adolescence or young adulthood and can cause significant disfigurement and psychosocial impairment. This disorder is under-recognized due to patient discomfort to disclose excoriation habits or lack of behavior awareness. It is imperative that dermatologists accurately diagnose and treat this disorder to minimize long-term damage to the skin. This review aims to provide an overview of the diagnosis and treatment options for AE.

Development of a Skin-Directed Scoring System for Stevens-Johnson Syndrome and Epidermal Necrolysis: A Delphi Consensus Exercise.

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Psoriasis drugs in the medicare population: dermatologists' spending and prescription patterns.

PURPOSE: Over the past decade, many new biologic and small-molecule drugs have been approved for psoriasis. These specialty drugs tend to be expensive and place financial burden on the healthcare system as well as patients. This study aims to explore trends in Medicare Part D spending and prescription patterns for psoriasis drugs by dermatologists. METHODS: The Centers for Medicare and Medicaid Services' (CMS) Medicare Part D Public Use Files from 2013 to 2017 were utilized to examine prescription rates and pricing FDA-approved psoriasis drugs. RESULTS: From 2013 to 2017, psoriasis drugs accounted for 41% of total Medicare Part D spending by dermatologists in the database, of which biologics accounted for 86.5%. The proportion of psoriasis-related spending increased from 36% of total spending in 2013 to 53% in 2017. Prescriptions of etanercept decreased while prescribers of newly approved drugs increased significantly. The cost per day of biologics were significantly variable in 2013 but converged toward similar costs in 2017. CONCLUSION: Psoriasis prescriptions comprise a large, increasing proportion of Medicare Part D spending related to dermatology. These increasing costs have significant implications for the healthcare system and affect out-of-pocket costs for patients who rely on such medications.

Alopecia areata as an immune-related adverse event of immune checkpoint inhibitors: A review.

Immune checkpoint inhibitors (ICI) improve the ability of the immune system to target cancer cells by blocking signaling through either the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD-1) receptor, or its ligand (PD-L1). They have been found to cause a variety of immune-related adverse events (irAEs) including a form of nonscarring alopecia that resembles alopecia areata (AA) in presentation and histology. Clinical features of ICI-induced AA are poorly described. We queried the Pubmed database for cases of AA secondary to ICI use reporting on extent of hair loss, treatments attempted, alopecia outcome, and time of follow-up with 13 cases identified. Although most patients had localized hair loss with subsequent regrowth, four of them experienced extensive and persistent AA, lasting up to a year. All but one patient continued ICI after the onset of hair loss. Many used topical corticosteroids with varying outcomes. Possible prognostic factors for severe and persistent disease may include young age and male sex. However, the low number of reported cases limits the generalizability of these findings. Tumor response was positive in every case of immune-induced AA where it was reported. Further investigation will be needed to better characterize clinical features of this irAE, risk factors for persistent disease, and determine its optimal management.

Stevens-Johnson syndrome and toxic epidermal necrolysis-like reactions to checkpoint inhibitors: a systematic review.

The use of checkpoint inhibitors for treatment of advanced malignancies is increasing. Rashes, pruritus, and more rarely, reactions resembling Stevens-Johnsons syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur secondary to checkpoint inhibitors. To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of SJS or TEN associated with checkpoint inhibitors. We identified 18 cases of SJS or TEN-like reactions to checkpoint inhibitors in the literature. There were 12 cases of SJS-like rashes with median time to onset of 5.6 weeks (average of 8.9 weeks), of which five were delayed to week 8 or later from checkpoint inhibitor initiation. The five TEN-like reactions had a median time to onset of 4 weeks (average of 5.38 weeks), of which two were delayed to week 6 or later. SJS/TEN-like reactions to nivolumab (seven cases) had median onset time of 3 weeks, whereas five cases secondary to pembrolizumab had median onset time of 11 weeks. Seven cases in this study described prodromal rashes, which varied from localized papular rashes to generalized morbilliform rashes, prior to evolution into SJS or TEN-like patterns. SJS-like patterns generally improved well on systemic treatment/supportive care and no cases of death were identified, but mortality occurred in three of five patients with TEN-like reactions. Dermatologists should consider the possibility for unique features of SJS/TEN in response to checkpoint inhibitors. Additional studies will be necessary to further characterize SJS/TEN-like eruptions on checkpoint inhibitors and determine the optimal management of these cases.

Off-label studies on apremilast in dermatology: a review.

Purpose: Apremilast is a phosphodiesterase-4 inhibitor FDA approved for psoriatic arthritis and moderate to severe plaque psoriasis. In recent years, multiple studies have suggested other potential uses for apremilast in dermatology. A summary of these various studies will be a valuable aid to dermatologists considering apremilast for an alternative indication.Materials and methods: The PubMed/MEDLINE and ClinicalTrials.gov databases were queried with the term 'apremilast,' with results manually screened to identify published data on off-label uses of apremilast. The article was structured by the quality of evidence available.Results: Apremilast use in dermatology beyond plaque psoriasis and psoriatic arthritis is frequently described in the literature, with a mixture of positive and negative results. Randomized controlled data is available for Behçet's disease, hidradenitis suppurativa, nail/scalp/palmoplantar psoriasis, alopecia areata, and atopic dermatitis.Conclusion: The relatively safe adverse effect profile of apremilast and its broad immunomodulatory characteristics may make it a promising option in the future for patients with difficult to treat diseases in dermatology, refractory to first line therapies, but further studies will be necessary to clarify its role.