title: Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis.
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.
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ 0793-1080, USA. thomas.hultsch@novartis.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Hultsch
authors.forename: Alexander
authors.initials: A
authors.lastname: Kapp
authors.forename: Jonathan
authors.initials: J
authors.lastname: Spergel
mesh_terms: D000287:Administration, Topical; D000818:Animals; D065095:Calcineurin Inhibitors; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D009824:Ointments; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D018570:Risk Assessment; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009824:Ointments; C117268:pimecrolimus; D016559:Tacrolimus