title: Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: clinical and immunological effects.
abstract: Cyclosporin A (CsA) is an effective and well-tolerated treatment for severe childhood atopic dermatitis (AD). By starting at a low dose, the therapeutic safety should be further increased. The aim of this study was to evaluate low-dose CsA in childhood AD with respect to clinical outcome and modulation of T-cell dysregulation. In an open prospective study, 10 children (age: 22-106 months) with severe AD (mean objective SCORAD score > 40 on two baseline measurements at a minimum interval of 2 weeks) were treated with CsA solution for 8 weeks. All patients received a starting dose of 2.5 mg/kg/day, which was increased stepwise in non-responders to a maximum of dose of 5 mg/kg/day. Disease activity was monitored using the SCORAD index. The frequency of cytokine-producing peripheral blood T lymphocytes was analyzed by intracellular cytokine staining, and T-cell numbers were measured by fluorescence-activated cell sorter (FACS) analysis. Twenty healthy age-matched children were included as controls for the immunological data. Nine of the 10 patients had a SCORAD reduction of at least 35%. In seven patients this was achieved with low-dose CsA at 2.5 mg/kg/day (n = 4) and 3.5 mg kg/day (n = 3). Seven of the nine responders experienced no relapse within the 4-week follow-up period. At baseline the percentage of interleukin-4 (IL-4), IL-13, and human leucocyte antigen (HLA)-DR-positive CD3(+) cells was higher in the patient group than in the controls. After CsA treatment there was a significant reduction in interferon-gamma (IFN-gamma), IL-2, IL-4, IL-13, and HLA-DR-positive CD3(+) cells. Hence, in severe pediatric AD, CsA microemulsion, when started at a low dose (2.5 mg/kg/day), improves clinical measures of disease, reduces T-lymphocyte cytokine production, and regulates T-cell activation.
authors.affiliation: Charité Campus Virchow-Klinikum, Department of Pediatric Pneumology and Immunology, Humboldt University of Berlin, Berlin, Germany. rita.bunikowski@charite.de
authors.forename: R
authors.initials: R
authors.lastname: Bunikowski
authors.forename: D
authors.initials: D
authors.lastname: Staab
authors.forename: F
authors.initials: F
authors.lastname: Kussebi
authors.forename: M
authors.initials: M
authors.lastname: Bräutigam
authors.forename: G
authors.initials: G
authors.lastname: Weidinger
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: U
authors.initials: U
authors.lastname: Wahn
mesh_terms: D000293:Adolescent; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016131:Lymphocyte Subsets; D008297:Male; D012720:Severity of Illness Index
chemical_list: D018793:Interleukin-13; D015847:Interleukin-4; D016572:Cyclosporine