Letter to the Editor| Volume 131, P1-4, May 2020

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Toxic epidermal necrolysis accompanied by several immune-related adverse events developed after discontinuation of nivolumab

Published:April 02, 2020DOI:
      Common cutaneous events, such as lichenoid reactions and vitiligo, induced by immune checkpoint inhibitors (ICs) are typically of low grade, while toxic epidermal necrolysis (TEN) as an immune-related adverse event (irAE) is quite rare. However, gene expression profile of lesional skin from anti–programmed cell death-1 (PD-1)–related cutaneous AEs resembled Stevens-Johnson syndrome (SJS)/TEN-like pattern [
      • Goldinger S.M.
      • Stieger P.
      • Meier B.
      • Micaletto S.
      • Contassot E.
      • French L.E.
      • et al.
      Cytotoxic cutaneous adverse drug reactions during anti-PD-1 therapy.
      ], suggesting that anti–PD-1 antibody could induce SJS/TEN-like reactions at least in some patients and it should be considered during treatment with ICs. Despite the increase in usage, predictive markers for disease progression to severe irAEs remain unelucidated. We encountered a case of TEN concomitant with other irAEs developed after several months of nivolumab therapy. To understand the cytokine profile and immune regulation in our case, the cytokine levels and the state of regulatory T cells (Tregs) were analysed during the clinical course.
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        • Goldinger S.M.
        • Stieger P.
        • Meier B.
        • Micaletto S.
        • Contassot E.
        • French L.E.
        • et al.
        Cytotoxic cutaneous adverse drug reactions during anti-PD-1 therapy.
        Clin Canc Res. 2016; 22: 4023-4029
        • Wang L.L.
        • Patel G.
        • Chiesa-Fuxench Z.C.
        • McGettigan S.
        • Schuchter L.
        • Mitchell TC.
        • et al.
        Timing of onset of adverse cutaneous reactions associated with programmed cell death protein 1 inhibitor therapy.
        JAMA Dermatol. 2018; 154: 1057-1061
        • Hwang A.
        • Iskandar A.
        • Dasanu C.A.
        Stevens-Johnson syndrome manifesting late in the course of pembrolizumab therapy.
        J Oncol Pharm Pract. 2019; 25: 1520-1522
        • Fujita H.
        • Matsukura S.
        • Watanabe T.
        • Komitsu N.
        • Watanabe Y.
        • Takahashi Y.
        • et al.
        The serum level of HMGB1 (high mobility group box 1 protein) is preferentially high in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms.
        Br J Dermatol. 2014; 171: 1585-1588
        • Tarhini A.A.
        • Zahoor H.
        • Lin Y.
        • Malhotra U.
        • Sander C.
        • Butterfield L.H.
        • et al.
        Baseline circulating IL-17 predicts toxicity while TGF-beta 1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma.
        J Immunother Cancer. 2015; 3: 39
        • Lim S.Y.
        • Lee J.H.
        • Gide T.N.
        • Menzies A.M.
        • Guminski A.
        • Carlino M.S.
        • et al.
        Circulating cytokines predict immune-related toxicity in melanoma patients receiving anti-PD-1-based immunotherapy.
        Clin Canc Res. 2019; 25: 1557-1563
        • Tanaka R.
        • Okiyama N.
        • Okune M.
        • Ishitsuka Y.
        • Watanabe R.
        • Furuta J.
        • et al.
        Serum level of interleukin-6 is increased in nivolumab-associated psoriasiform dermatitis and tumor necrosis factor-α is a biomarker of nivolumab recativity.
        J Dermatol Sci. 2017; 86: 71-73
        • Lin W.W.
        • Karin M.
        A cytokine-mediated link between innate immunity inflammation, and cancer.
        J Clin Invest. 2007; 117: 1175-1183
        • Goodman W.A.
        • Levine A.D.
        • Massari J.V.
        • Sugiyama H.
        • McCormick T.S.
        • Cooper K.D.
        IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells.
        J Immunol. 2009; 183: 3170-3176
        • Shiomi A.
        • Usui T.
        • Mimori T.
        GM-CSF as a therapeutic target in autoimmune diseases.
        Inflamm Regen. 2016; 5: 36-38