title: Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.
abstract: Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
  
  
  
  In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis.
  
  
  
  Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Hofmann
authors.affiliation: Department of Dermatology, University Hospital Tübingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Forschner
authors.affiliation: Department of Dermatology, University Hospital Mainz, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Loquai
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Goldinger
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.affiliation: Department of Dermatology, University Hospital Mainz, Germany.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Schmidgen
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Jochen S
authors.initials: JS
authors.lastname: Utikal
authors.affiliation: Department of Dermatology, University Hospital Magdeburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Göppner
authors.affiliation: Department of Dermatology, University Hospital Heidelberg, Germany.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Hassel
authors.affiliation: Department of Dermatology, University Hospital Dresden, Germany.
authors.forename: Friedegund
authors.initials: F
authors.lastname: Meier
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian-University (LMU) Munich, Germany.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Tietze
authors.affiliation: Department of Dermatology, University Hospital Tübingen, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Thomas
authors.affiliation: Department of Dermatology, University Hospital Münster, Münster, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Weishaupt
authors.affiliation: Department of Dermatology, University Hospital RWTH Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Leverkus
authors.affiliation: Department of Dermatology, University Hospital RWTH Aachen, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Wahl
authors.affiliation: Department of Dermatology, University Hospital Dresden, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Dietrich
authors.affiliation: Department of Dermatology, University Hospital Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kirchberger
authors.affiliation: Department of Dermatology, University Hospital Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eigentler
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian-University (LMU) Munich, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
authors.affiliation: Department of Dermatology, University Hospital Würzburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Gesierich
authors.affiliation: III. Medical Department, Technische Universität München (TUM), Munich, Germany.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Krackhardt
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
authors.forename: Gerold
authors.initials: G
authors.lastname: Schuler
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de.
authors.forename: Lucie M
authors.initials: LM
authors.lastname: Heinzerling
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003875:Drug Eruptions / Q000209:etiology; D004700:Endocrine System Diseases / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D000074324:Ipilimumab; D007674:Kidney Diseases / Q000139:chemically induced; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: Adverse event; Anti-PD-1; Checkpoint inhibitors; Immune-related; Nivolumab; Pembrolizumab; Side-effect; Tolerability; Toxicity