The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted therapeutics. We aimed to compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus systemic/cutaneous lymphocyte antigen (-) "polar" CD4/CD8 and activated T-cell subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood, with appropriate clinical correlations. Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4/CD8 T cells, with inducible co-stimulator molecule and HLA-DR defining mid- and long-term T-cell activation, respectively. We compared peripheral blood from 47 patients with ichthyosis (congenital ichthyosiform erythroderma, lamellar ichthyosis, epidermolytic ichthyosis, and Netherton syndrome) with 43 patients with atopic dermatitis and 24 patients with psoriasis and 59 age-matched controls. Clinical measures included the ichthyosis severity score, with subsets for erythema and scaling, transepidermal water loss, and pruritus. All ichthyoses had excessive inducible co-stimulator molecule activation (P < 0.001), particularly epidermolytic ichthyosis. Significantly elevated IL-17- (P < 0.05) and IL-22-producing (P < 0.01) T cells characterized ichthyoses, mainly Netherton syndrome and congenital ichthyosiform erythroderma (P < 0.05). Increased T helper 2/cytotoxic T cell 2/T helper 9 (P < 0.05) and similar IFN-γ frequencies (P > 0.1) versus controls were also noted. IL-17/IL-22-producing cells clustered with clinical measures, whereas IFN-γ clustered with age. Our data show peripheral blood IL-17/IL-22 activation across the ichthyoses, correlating with clinical measures. Targeted therapies should dissect the relative contribution of polar cytokines to disease pathogenesis.
Transepidermal water loss (TEWL) is a noninvasive biomarker for epidermal barrier integrity. TEWL has been a useful measurement in clinical trials for potential new therapies. 1,2 However, its incorporation into objective assessments in the clinic setting has been limited by the size and cost of most currently available devices, including the AquaFlux AF200 ® ("AquaFlux") unit (Biox Systems, LTD), which is most often used by researchers to measure TEWL. A pocket-sized, lightweight device has recently become available, the gpskin Barrier Light ® ("gpskin") (gpower, Inc), which transmits data using Bluetooth, costs much less than traditional devices, and does not require an equilibration period before use. The ichthyoses are a group of genetic disorders characterized by scaling, skin thickening, and cutaneous inflammation, which are thought to represent responses to the epidermal barrier abnormality. 3
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