ATOPIC DERMATITIS - aspects of defence defects

Atopic dermatitis (AD) is an inflammatory skin disease, typically with a chronic relapsing course and a defective skin barrier function. Recently, mutations of the skin barrier gene encoding filaggrin have been reported in a portion of the patients. In this thesis some aspects of defence defects in AD were studied. In paper I, the risk of developing any cancer was increased by 13%. Excess risks were observed for cancers of the esophagus, pancreas, brain, and lung and for lymphoma. There was a nonsignificant 50% excess risk for nonmelanoma skin cancer. Malignant melanoma did not occur more often than expected. The observed risk elevations, all of borderline statistical significance, should be interpreted cautiously. We could not control for possible confounding by cases of cancer caused by smoking, and the combination of multiple significance testing and few observed patients may have generated chance findings. In paper II, the findings suggest that a moisturiser containing both urea and sodium chloride seems somewhat more effective than the same moisturiser without sodium chloride, at least concerning the ability to reverse impedance indices of atopic skin towards normal, an effect ascribed mainly to changes in hydration of the stratum corneum. However, the clinical significance of the impedance measurements is somewhat premature to decide. In paper III, the findings indicate that barrier function and hydration, and certain patterns of electrical impedance of AD skin are abnormal compared with normal skin. Moreover, there was an increase in hydration in patients’ skin after treatment and a reversal of certain impedance indices towards normal. The findings demonstrate that the used moisturiser changes some biophysical parameters when applied to atopic skin. In addition, a technique based on electrical impedance seems to give valuable information in atopic skin studies, especially the effects of moisturisers. In paper IV, the distribution of somatostatin receptors (SSTR) 1-5 in skin from patients with AD or psoriasis as well as normal control skin was studied. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin. LIST OF PUBLICATIONS This thesis is based on the following four articles, which will be referred to by their Roman numbers: I. Hagströmer L, Ye W, Nyrén O, Emtestam L. Incidence of cancer among patients with atopic dermatitis. Arch Dermatol. 2005;141:1123-1127. II. Hagströmer L, Nyrén M, Emtestam L. Do urea and sodium chloride together increase the efficacy of moisturisers in atopic dermatitis skin? A comparative, double-blind, randomised study. Skin Pharmacol Appl Skin Physiol 2001:14;27-33. III. Hagströmer L, Kuzmina N, Lapins J, Talme T, Emtestam L. Biophysical assessment of atopic dermatitis skin and effects of a moisturiser. Clin Exp Dermatol. 2006:31;272-277. IV. Hagströmer L, Emtestam L, Stridsberg M, Talme T. Expression pattern of somatostatin receptor subtypes 1 to 5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis. Exp Dermatol. 2006:15;950-957. RELATED PUBLICATIONS Dou Y, Hagströmer L, Emtestam L, Johansson O. Increased nerve growth factor and its receptors in atopic dermatitis: an immunohistochemical study. Arch Dermatol Res 2006:298;3137. Kuzmina N, Hagströmer L, Nyrén M, Emtestam L. Basal electrical impedance in relation to sodium lauryl sulphate-induced skin reactions a comparison of patients with eczema and healthy controls. Skin Res Technol. 2003:9;357-362. Kuzmina N, Hagströmer L, Emtestam L. Urea and sodium chloride in moisturisers for skin of elderly: a comparative, double-blind, randomised study. Skin Pharmacol Appl Skin Physiol 2002:15;166-174. Nyrén M, Hagströmer L, Emtestam L. Instrumental measurement of the Mantoux test: Differential effects of tuberculin and sodium lauryl sulphate on impedance response pattern in human skin. Dermatology 2000:201;212-217. Nyrén, M, Hagströmer L, Emtestam L. On assessment of skin reactivity using electrical impedance. In: Electrical bioimpedance methods: applications to medicine and biotechnology. Riu PJ, Rosell J, Bragós R, Casas Ó (Eds). Ann N Y Acad Sci 1999:873; pp. 214-220.