Immediate Wheal Reactivity to Autologous Sweat in Atopic Dermatitis Is Associated with Clinical Severity, Serum Total and Specific IgE and Sweat Tryptase Activity.

BACKGROUND: Sweating can worsen atopic dermatitis (AD). The purpose of this work was to study the associations between reactivity to autologous sweat and the clinical severity of AD as well as investigate the possible wheal-inducing factors of sweat. METHODS: Intracutaneous skin tests with autologous sweat were performed on 50 AD patients and 24 control subjects. In skin biopsies, tryptase and PAR-2 were enzyme and immunohistochemically stained. The associations between skin test reactivity and sweat histamine concentration, tryptase or chymase activity levels, tryptase or PAR-2 expression and AD clinical severity or IgE levels were investigated. RESULTS: The wheal reactions in the intracutaneous tests with autologous sweat were positive, weakly positive and negative in 38, 34 and 28% of the AD patients, respectively, and in 4, 46 and 50% of the healthy controls, respectively (p = 0.008). In AD, the wheal reaction was associated significantly with clinical severity, serum total and specific IgE levels and sweat tryptase activity, but not with sweat histamine and chymase. In nonlesional AD skin, the percentage of PAR-2+ mast cells (MCs) or the number of tryptase+ MCs did not differ significantly between the intracutaneous test reactivity groups. CONCLUSION: Reactivity to autologous sweat correlates with the clinical severity of AD, and tryptase may be one of the factors involved in the sweat-induced wheal.

Epidermal Expression of Filaggrin/Profilaggrin Is Decreased in Atopic Dermatitis: Reverse Association With Mast Cell Tryptase and IL-6 but Not With Clinical Severity.

BACKGROUND: A decrease in filaggrin expression contributes to the pathogenesis of atopic dermatitis (AD) and can be modified by inflammatory factors. OBJECTIVES: The aim of this study was to determine the correlation of (pro)filaggrin (filaggrin and profilaggrin) expression with clinical severity in AD and with mast cell (MC) tryptase, chymase, and IL-6. METHODS: Punch biopsies were collected from 17 patients with moderate-to-severe AD and from 10 psoriatic patients. Atopic dermatitis severity was measured using different clinical parameters. (Pro)filaggrin, MC tryptase, chymase, and IL-6 were stained using immunohistochemical, enzymehistochemical, and sequential double-staining methods. RESULTS: (Pro)filaggrin expression was lower in the lesional than in the nonlesional granular layer in AD and was correlated negatively with itch severity but not with other severity parameters. (Pro)filaggrin expression was also decreased in the psoriatic lesions. In AD, (pro)filaggrin expression correlated negatively with the number of tryptase MCs in the nonlesional granular layer and with IL-6 MCs in both the nonlesional and lesional granular layers. CONCLUSION: (Pro)filaggrin expression is decreased in AD and is reversely associated with MC tryptase and IL-6. However, it does not associate with disease severity, and it was also decreased in psoriasis.

Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation.

Mast cells are increasingly present in the lesional skin of chronic skin inflammatory diseases including psoriasis and basal cell carcinoma (BCC). It has previously been shown that proteinase-activated receptor (PAR)-2 is expressed by mast cells, and tryptase is a potent activator of this receptor. In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH(2). Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PAR-2 activating peptide resulted in an increased secretion of IL-8, but no histamine release was observed. Furthermore, both PAR-2 and IL-8 were co-localized to the same tryptase-positive mast cells in the lesional BCC skin. These results show that mast cells express increased levels of PAR-2 in chronic skin inflammation. Also, mast cells can be activated by a PAR-2 agonist to secrete IL-8, a chemokine which can contribute to the progress of inflammation.