Mucocutaneous adverse events to immune checkpoint inhibitors

Frontiers in Allergy, Journal Year: 2023, Volume and Issue: 4

Published: March 2, 2023

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Since the approval of ipilimumab in 2011, a total nine ICIs gained indications for various solid and hematologic malignancies. The expanding use oncology underscores need diagnosis treatment expertise immune related adverse events (irAE). Cutaneous toxicities are earliest most common irAE this class In addition to more frequent reactions including vitiligo, lichenoid dermatitis, psoriasiform other less skin bullous dermatoses, neutrophilic autoimmune dermato-rheumatologic diseases been reported. Even though than 3% cutaneous irAEs (irCAEs) classified as grade 3 or higher events, irCAEs can greatly impact quality life. Appropriate management is critical avoid unwarranted interruptions discontinuation lifesaving immunotherapy.

Language: Английский

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Pembrolizumab-induced lichenoid dermatitis treated with dupilumab

JAAD Case Reports, Journal Year: 2023, Volume and Issue: 37, P. 13 - 15

Published: May 16, 2023

Immune checkpoint inhibitor (ICI) therapies have revolutionized cancer treatment and are being increasingly used for many subtypes. However, the development of cutaneous immune-related adverse events (cirAEs) can severely impact quality life result in discontinuation ICI therapy. Lichenoid dermatitis is a cirAE that typically occurs due to anti–PD-1 anti–programmed death receptor ligand 1 therapy rarely with anti–cytotoxic T-lymphocyte-associate antigen 4 treatment, and, although pruritus common, clinical presentation be broad.1Ellis S.R. Vierra A.T. Millsop J.W. Lacouture M.E. Kiuru M. Dermatologic toxicities immune therapy: review histopathologic features.J Am Acad Dermatol. 2020; 83: 1130-1143https://doi.org/10.1016/j.jaad.2020.04.105Google Scholar In addition systematically characterizing ICI-induced cirAEs,2Nadelmann E.R. Yeh J.E. Chen S.T. Management patients treated inhibitors: systematic review.JAMA Oncol. 2022; 8: 130-138https://doi.org/10.1001/jamaoncol.2021.4318Google molecular phenotyping approaches, such as RNA situ hybridization (RISH),3Wang A. Fogel A.L. Murphy M.J. et al.Cytokine permits individualized biopsies psoriasis atopic dermatitis.JID Innov. 2021; 1100021https://doi.org/10.1016/j.xjidi.2021.100021Google potential better personalize diagnosis selection. We report 2 cases recalcitrant lichenoid found type inflammatory cytokine interleukin-13 (IL-13) on biopsy using RISH successfully dupilumab. Patient 68-year-old woman seropositive rheumatoid arthritis adalimumab, hydroxychloroquine, intermittent prednisone, whom pancreatic adenocarcinoma developed she was PD-1 pembrolizumab. Subsequently, an extensive pruritic rash patient. Physical examination demonstrated pink-violaceous, scaly papules coalescing into plaques scattered chest, back, arms, hands, legs (Fig 1, A). Biopsies from right side left thigh dorsal aspect hand showed band infiltrate lymphocytes abundant eosinophils obscures dermoepidermal junction, which consistent anti–PD-1-induced B). She acitretin 17.5 mg topical halobetasol but itch persisted. Pembrolizumab held worsening rash. staining results patient's samples expression IL-13 C). interferon gamma (IFN-γ), IL-4, 3 IL-17A were negative. started receiving dupilumab, resulted sustained improvement D), patient able restart her remains pembrolizumab 77-year-old man metastatic clear cell renal carcinoma, pembrolizumab, resulting pink large confluent flanks, abdomen, thighs, buttocks 2, Biopsy abdomen band-like concerning possible induced B) analysis IFN-γ, Past daily methotrexate 12.5 weekly unsuccessful. He cleared within month D) reinstated. this case series we describe use IL-4 α-antagonist blocks both signaling,4Beck L.A. Thaçi D. Hamilton J.D. al.Dupilumab adults moderate-to-severe dermatitis.N Engl J Med. 2014; 371: 130-139https://doi.org/10.1056/NEJMoa1314768Google setting Although there substantial variability manifestation skin-oriented based factors including specific agent administered underlying malignancy,5Nikolaou V.A. Apalla Z. Carrera C. al.Clinical associations classification inhibitor-induced toxicities: multicentre study European Academy Dermatology Venereology Task Force Cancer Patients.Br 187: 962-969https://doi.org/10.1111/bjd.21781Google reactions among most common cirAEs when severe, cause interruption or immunotherapy treatment.2Nadelmann Scholar,6Geisler A.N. Phillips G.S. Barrios D.M. al.Immune inhibitor-related dermatologic events.J 1255-1268https://doi.org/10.1016/j.jaad.2020.03.132Google Therefore, need identify pathogenesis-based targets expand therapeutic armamentarium refractory beyond steroids discontinuation. Certain features may help distinguish classic lichen planus, presence eosinophils,7Tetzlaff M.T. Nagarajan P. Chon S. al.Lichenoid toxicity blockade detailed clinicopathologic features.Am Dermatopathol. 2017; 39: 121-129https://doi.org/10.1097/DAD.0000000000000688Google precise pathophysiology unclear,8Postow M.A. Sidlow R. Hellmann M.D. Immune-related associated blockade.N 2018; 378: 158-168https://doi.org/10.1056/NEJMra1703481Google one has phenotypic similarities between acute graft versus host disease interface cirAEs, suggesting potentially shared pathophysiologic mechanisms.9Almodovar Cruz G.E. Kaunitz G. Stein subsets anti-PD-1 resemble more than planus.J Cutan Pathol. 49: 701-708https://doi.org/10.1111/cup.14242Google expressed biopsies, inflammation play role pathogenesis provides rationale IL-4Rα antagonism. To our knowledge, first dupilumab dermatitis, demonstrating safe, rapid, improvement. Importantly, initiation allowed reinitiation elevated levels compared recent planus.10Pietschke K. Holstein J. Meier al.The planus dominated by IFN-γ IL-21. A basis JAK1 inhibition.Exp 30: 262-270https://doi.org/10.1111/exd.14226Google Scholar,11Pousti B.T. Jin Sklovar L. planus.Cutis. 107: E8-E10https://doi.org/10.12788/cutis.0232Google pembrolizumab-induced no reflect distinct mechanism dermatitis. studies needed compare these overlapping, entities. Dupilumab also been efficacy tolerability bullous pemphigoid,12Abdat Waldman R.A. de Bedout V. novel pemphigoid: multicenter series.J 46-52https://doi.org/10.1016/j.jaad.2020.01.089Google indicating its relevance other subtypes, immunobullous. Altogether, highlight value technologies guide selection, suggest effective strategy treating without interrupting therapy; however, further necessary validate results. Dr Vesely's spouse employee Regeneron Pharmaceuticals, maker Damsky consultant Pfizer, Eli Lilly, TWi Biotechnology, received research funding receives licensing fees EMD/Millipore/Sigma. Drs Park E. conflicts interest declare.

Language: Английский

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Immune cell subsets in interface cutaneous immune‐related adverse events associated with anti‐PD ‐1 therapy resemble acute graft versus host disease more than lichen planus

Journal of Cutaneous Pathology, Journal Year: 2022, Volume and Issue: 49(8), P. 701 - 708

Published: April 21, 2022

Checkpoint immunotherapy is frequently associated with cutaneous immune-related adverse events (cirAEs), and among those, the most common subtype shows interface reaction patterns that have been likened to lichen planus (LP); however, acute graft versus host disease (aGVHD) may be a closer histopathologic comparator. We used quantitative pathology compare immunologic composition of anti-PD-1-associated reactions LP aGVHD assess for similarities differences between these eruptions.Immunohistochemistry CD4, CD8, CD68, PD-1, PD-L1 was performed on formalin-fixed paraffin-embedded tissue from patients anti-PD-1 cirAEs (n = 4), 9), or 5). Densities immune cell subsets expressing each marker were quantified using HALO image analysis module. Plasma eosinophil density routine H&E slides.Specimens showed equivalent total densities those aGVHD. Patients higher infiltration, absolute T-cell densities, increased CD8 proportion, reduced histiocytic component. The cases highest plasma counts all aGVHD.The in more closely resembles response seen than within our cohort. This warrants look via advanced analytics implications shared pathogenesis potential treatment options.

Language: Английский

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Immune checkpoint inhibitor-induced cutaneous toxicities: a review of histopathologic and clinical features

Human Pathology, Journal Year: 2023, Volume and Issue: 140, P. 144 - 172

Published: May 2, 2023

Language: Английский

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