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Chronic Candida species infection of the skin and mucosal membranes is viewed as a group of disorders all sharing a similar clinical condition, the susceptibility to localized fungal infections, which can be isolated or as a feature associated with various other entities. Although the pathogenesis underlying such a tendency had previously been poorly understood, the last decade has witnessed significant progress in revealing the molecular and immunologic mechanisms involved in antifungal immunity. T(H)17 cells and their specific cytokines (IL-17A and IL-17F cytokines and IL-22) are the main players in conferring antifungal protection. Autoimmune polyendocrinopathy and ectodermal dystrophy and hyper-IgE syndrome are 2 entities caused by different genetic mutations affecting distinct immune pathways but eventually share a similar clinical phenotype of Candida species infection. Impaired T(H)17 responses, although mediated by different mechanisms, seem to underlie this common feature: neutralizing autoantibodies against IL-17A and 1L-22 are involved in patients with autoimmune polyendocrinopathy and ectodermal dystrophy syndrome, whereas abnormal T(H)17 proliferation and IL-17 production are observed in the latter. Although various degrees of T(H)17 dysfunction were also observed in most cases of isolated chronic mucocutaneous candidiasis, only in very few families was a distinct mutation detected (caspase recruitment domain family, member 9 [CARD9]), thus indicating certain forms of chronic mucocutaneous candidiasis as monogenic with a Mendelian pattern of inheritance. Hopefully, these data will open the way for further searches for other genes and for introducing new treatment modalities., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

The clinical phenotype of psoriasis results from infiltration of T cells in the skin and elaboration of inflammatory cytokines. Interleukin (IL)-12 and, more recently, IL-23 have been implicated in the pathogenesis of psoriatic lesions. New therapies, including a monoclonal antibody against a subunit shared by IL-12 and IL-23, have been developed to treat psoriasis. Our purpose was to review the literature on IL-12 and IL-23 as a basis for understanding the use of anti-IL-12/IL-23 therapy for psoriasis. A review of English-language articles was performed using PubMed to identify articles pertaining to IL-12, IL-23, and psoriasis. IL-12 and IL-23 share a common subunit (p40) and have a distinct subunit (p35 and p19, respectively). Transgenic mice that overexpress IL-12 p40 develop inflammatory skin lesions. Both IL-12 knockout mice, which are deficient in IL-12, and human beings with a genetic IL-12 deficiency show increased susceptibility to intracellular pathogens and defective delayed-type hypersensitivity responses. These genetic deficiency states suggest the potential for adverse side effects from clinical administration of anti IL-12 p40 therapy. IL-12 p40 antibody was well tolerated in a phase I clinical trial with few adverse events and substantial improvements in psoriasis in most individuals. There was dose-dependent efficacy and substantial improvement in a larger cohort of patients in a phase II clinical trial. Larger and longer trials of anti IL-12/IL-23 therapies are needed to assess their clinical use and potential for infection and other adverse events.