Management of Local Skin Reactions Caused by 5-FU 4% Cream for the Treatment of Actinic Keratosis: A Delphi Consensus

Gabriella Brancaccio; Giulia Briatico; Zoe Apalla; Reinhard Dummer; Jan Eklind; Nicole Basset Seguin; Brigitte Dreno; Maria Concetta Fargnoli; Pascale Guitera; Markus V. Heppt; Christoph Hoeller; Thomas Jouary; Aimilios Lallas; Ulrikke Lei; Ulrike Leiter; Josep Malvehy; David  Moreno Ramirez; John Paoli; Ketty Peris; Susanna Puig; Philippe Saiag; Eggert Stockfleth; Wilhelm Stolz; Alexander J. Stratigos; Class Ulrich; Ann-Marie Wennberg; Iris Zalaudek; Giuseppe Argenziano

doi:10.5826/dpc.1502a5787

Management of Local Skin Reactions Caused by 5-FU 4% Cream for the Treatment of Actinic Keratosis: A Delphi Consensus

Authors

Gabriella Brancaccio Dermatology Unit, University of Campania, Naples Italy
Giulia Briatico Dermatology Unit, University of Campania, Naples Italy
Zoe Apalla Second Dermatology Department, Aristotle University of Thessaloniki, Greece
Reinhard Dummer University Hospital Zurich and Kantonsspital Aarau
Jan Eklind Diagnostiskt Centrum Hud, Stockholm, Sweden
Nicole Basset Seguin Dermatology Department, Saint-Louis Hospital, Paris, France
Brigitte Dreno Dermatology Department, CHU Nantes, CIC 1413, CRCINA, University Nantes, Nantes, France.
Maria Concetta Fargnoli San Gallicano, Dermatological Institute, IRCCS, Rome, Italy
Pascale Guitera Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, and Melanoma Institute Australia and Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Markus V. Heppt Department of Dermatology, Uniklinikum Erlangen, Friedrich-Alexander University (FAU), Erlangen, Germany; Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN) and CCC Alliance WERA, Erlangen, Germany; Bavarian Cancer Research Center (BZKF), Erlangen, Germany
Christoph Hoeller Department of Dermatology, Medical University of Vienna, Austria
Thomas Jouary Dermatology Unit, Hospital Francois Mitterrand, Pau, France
Aimilios Lallas First Dermatology Department, Aristotle University of Thessaloniki, Greece
Ulrikke Lei Department of Dermatology and Allergy, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
Ulrike Leiter Center for Dermatooncology, Department of Dermatology, University Hospital of Tuebingen, Germany
Josep Malvehy Dermatology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, Barcelona, Spain
David Moreno Ramirez Medical-&-Surgical Dermatology Service. Hospital Universitario Virgen Macarena, Sevilla, Spain.
John Paoli Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden
Ketty Peris Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy.
Susanna Puig Dermatology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, Barcelona, Spain
Philippe Saiag Department of General and Oncologic Dermatology, Ambroise Paré hospital, APHP, & EA 4340 "Biomarkers in cancerology and haematooncology", UVSQ, Université Paris-Saclay, 92104 Boulogne-Billancourt, France.
Eggert Stockfleth Department of Dermatology, Ruhr-University, Bochum, Bochum, Germany.
Wilhelm Stolz Department of Dermatology, Faculty of Medicine, Ludwig-Maximilians-University, Munich
Alexander J. Stratigos First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece
Class Ulrich Charite-Universitiitsmedizin Berlin, Berlin, Germany.
Ann-Marie Wennberg Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Iris Zalaudek Department of Dermatology and Venereology of the Hospital Clinics Giuliano Isontino (ASUGI), Maggiore Hospital, Trieste, Italy.
Giuseppe Argenziano Dermatology Unit, University of Campania, Naples Italy

Keywords:

actinic keratosis , 5-fluorouracil, Local skin reactions

Abstract

Introduction: Treatments such as 4% 5-fluorouracil (5-FU) cream have demonstrated strong efficacy in lesion clearance of actinic keratosis; however, local skin reactions (LSR) during treatment remain a significant challenge, potentially affecting patient adherence.

Objective: We sought to build consensus on management of LSR associated with 4% 5-FU using a Delphi methodology.

Methods: Twenty-eight expert dermatologists participated in a 3-round Delphi process. Experts evaluated LSR management strategies, including emollients, antibiotics, steroids, and treatment discontinuation. Agreement levels were measured using a 7-point Likert scale. Consensus was categorized as high if >80% of votes were within the 5-7 rating range and low when >25% were in the 1-3 rating range, with <25% of the votes in the 6-7 rating range. Other combinations of votes were considered as having moderate agreement.

Results: High agreement was achieved for the following statements: the approved daily schedule (once daily for 4 weeks) is the most appropriate (92.9%); mild LSR generally do not require intervention and do not impact treatment adherence (96.4%); severe LSR may benefit from temporary treatment interruption and emollient use, ensuring adherence without compromising efficacy (92.9%). The use of emollients (in parallel with the treatment with 5-FU) was considered not needed by most (moderate consensus, 64.3%). Experts emphasized the importance of clear communication about LSR during baseline consultation to enhance patient compliance.

Conclusion: This consensus provides practical guidance for managing LSR induced by 4% 5-FU, ensuring high adherence and optimizing treatment outcomes. Further research is needed to validate these findings and explore alternative management approaches.

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