title: Mechanisms of action of topical therapies and the rationale for combination therapy.
abstract: The advent of new topical agents such as topical calcineurin inhibitors, as well as the reformulations of older agents in new vehicles, has broadened the treatment approaches to psoriasis and atopic dermatitis. The clinician must now consider additional novel physiologic pathways and mechanisms of action as well as expanding options for combination therapy. Combination therapy is especially beneficial when the selected agents possess differing mechanisms of action that provide additive or synergistic efficacy, reducing the required doses of the individual agents compared with monotherapy and potentially limiting side effects. Therapeutic approaches also can be rotated or used in various sequences for maintenance therapy. In psoriasis, a number of trials have demonstrated the effectiveness of combination therapy. Although combination therapy has not been extensively studied in atopic dermatitis, many practitioners combine topical corticosteroids and topical calcineurin inhibitors in their clinical practice because the two drug classes have different and possibly complementary mechanisms of action. For both diseases, the decision as to what agents are combined must also be tempered by patient type, disease presentation or severity, and patient preferences.
authors.affiliation: Department of Dermatology, University of Colorado School of Medicine, Denver, CO 80262, USA. david.norris@uchsc.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Norris
mesh_terms: D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002455:Cell Division / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors; D011565:Psoriasis / Q000188:drug therapy*; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000502:physiology; D012176:Retinoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014157:Transcription Factors / Q000037:antagonists & inhibitors
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D065095:Calcineurin Inhibitors; D016207:Cytokines; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018121:Receptors, Cytokine; D012176:Retinoids; D014157:Transcription Factors; D002762:Cholecalciferol