Immunomodulation and Safety of Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis

Vol. 211, No. 2, 2005

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Immunomodulation and Safety of Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis
Thomas Hultsch^a, Alexander Kapp^c, Jonathan Spergel^b

^aNovartis Pharmaceuticals Corporation, East Hanover, N.J., USA;
^bDepartment of Dermatology and Allergology, Hannover Medical University, Hannover, Germany;
^cDivision of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pa., USA

Address of Corresponding Author

Dermatology 2005;211:174-187 (DOI: 10.1159/000086739)

Key Words

Calcineurin inhibitors
Atopic dermatitis
Topical corticosteroids
Immunosuppression
Lymphoproliferative disease
Th1/Th2 balance

Abstract

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that primarily affects children. Topical corticosteroids have been the mainstay of treatment since the late 1950s. While providing excellent short-term efficacy, topical corticosteroid usage is limited by potential adverse effects, including impairment of the function and viability of Langerhans cells/dendritic cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream 1% (Elidel^®) and tacrolimus ointment 0.03 and 0.1% (Protopic^®) exhibit a more selective mechanism of action and do not affect Langerhans cells/dendritic cells. For the immune system of young children 'learning' to mount a balanced Th1/Th2 response, this selective effect has particular benefits. In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily used in children with mild and moderate AD, whereas tacrolimus is used preferentially in more severe cases. None of the topical calcineurin inhibitors have been associated with systemic immunosuppression-related malignancies known to occur following long-term sustained systemic immunosuppression with oral immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in transplant patients. Preclinical and clinical data suggest a greater skin selectivity and larger safety margin for topical pimecrolimus.

Author Contacts

Thomas Hultsch
Novartis Pharmaceuticals Corporation
East Hanover, NJ 07936-1080 (USA)
Tel. +1 862 778 3550, Fax +1 973 781 4214
E-Mail thomas.hultsch@novartis.com

Article Information

Number of Print Pages : 14
Number of Figures : 7, Number of Tables : 0, Number of References : 103

Medline Abstract (ID 16088174)

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