title: Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants.
abstract: Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Luger
authors.affiliation: Division of Pediatric Allergy-Immunology, Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.affiliation: Southern California Research, Mission Viejo, CA, USA.
authors.forename: Warner
authors.initials: W
authors.lastname: Carr
authors.affiliation: Academic Unit of Dermatology Research, Department of Infection and Immunity, The University of Sheffield, K Floor, The Medical School (RHH Tower), Sheffield, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Cork
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Deleuran
authors.affiliation: Departments of Pediatrics and Medicine, University of California, San Diego School of Medicine, Rady Children's Hospital, San Diego, CA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Eichenfield
authors.affiliation: Pediatric Allergy Unit, Children's University Hospital, Geneva, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Eigenmann
authors.affiliation: Department of Dermatology, University Clinics of Schleswig-Holstein, Kiel, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Clinica Dermatologica, Fondazione I.R.C.C.S. Ca' Granda "Ospedale Maggiore Policlinico", Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gelmetti
authors.affiliation: Department of Dermatology & Venereology, Otto-von-Guericke University of Magdeburg, Magdeburg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Gollnick
authors.affiliation: Allergy Center Ruhr, Ruhr-University Bochum, & Evangelisches Krankenhaus Bielefeld, Klinik für Kinder und Jugendmedizin, Bielefeld, Germany.
authors.forename: Eckard
authors.initials: E
authors.lastname: Hamelmann
authors.affiliation: Departments of Dermatology and Pediatrics, The University of Texas Medical School-Houston, Houston, TX, USA.
authors.forename: Adelaide A
authors.initials: AA
authors.lastname: Hebert
authors.affiliation: Food Allergy Referral Centre, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Muraro
authors.affiliation: Department of Dermatology, Maasstad Hospital, Rotterdam, the Netherlands.|Dermicis Skin Hospital, Alkmaar, the Netherlands.|Intermedica Dermatology and Hair Clinic, Boxmeer, the Netherlands.
authors.forename: Arnold P
authors.initials: AP
authors.lastname: Oranje
authors.affiliation: Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
authors.affiliation: Dermatology Department, INSERM 1056, Paul Sabatier University, Larrey Hospital, Toulouse, France.
authors.forename: Carle
authors.initials: C
authors.lastname: Paul
authors.affiliation: Department of Dermatology, Hospital de la Santa Creu i Sant Pau & Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Puig
authors.affiliation: Department of Dermatology and Allergology Biederstein, Christine Kühne-Center for Allergy Research and Education, Technische Universität München, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.affiliation: Departments of Pediatrics and Dermatology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Siegfried
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Pennsylvania, PA, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Spergel
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.affiliation: Service de Dermatologie et Dermatologie Pédiatrique Centre de référence pour les maladies rares de la peau, INSERM 1035, Université de Bordeaux, Bordeaux, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.affiliation: Department of Dermatology, Hospital Niño Jesus, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Torrelo
authors.affiliation: Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charite, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wahn
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D032921:Consensus; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D017410:Practice Guidelines as Topic; D016559:Tacrolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C117268:pimecrolimus; D016559:Tacrolimus
keywords: atopic dermatitis; eczema; infants; paediatric; pimecrolimus; safety; tacrolimus; topical calcineurin inhibitors; topical corticosteroids