Sex hormones and urticaria

Summary

Chronic urticaria is characterized by mast cells/basophils activation which initiate the inflammatory response. Pathogenetically, the disease may in many cases represent an autoimmune phenomenon. Altered function of the neuro-endocrine-immune system due to stress and other factors has also been implicated its pathogenesis. Sex hormones modulate immune and inflammatory cell functions, including mast cell secretion, and are regarded as responsible for gender and menstrual cycle phase-associated differential susceptibility and severity of some autoimmune and inflammatory diseases. Chronic urticaria is approximately twice more frequent in women than in men. In addition, urticaria may be associated with some diseases and conditions characterized by hormonal changes, including endocrinopathy, menstrual cycle, pregnancy, menopause and hormonal contraceptives or hormone replacement therapy. Hypersensitivity reactions to endogenous or exogenous female sex hormones have been implicated in the pathogenesis of urticarial lesions associated with estrogen and autoimmune progesterone dermatitis. We observed lower serum dehydroepiandrosterone sulfate (DHEA-S) concentration in patients with chronic urticaria with positive and negative response to autologous serum skin test. Thus, the influence of fluctuations in the hormonal milieu and altered sex hormone expression on the triggering-off, maintenance or aggravation of urticaria should be taken into account. In addition, the possible impact of estrogen mimetics, in the environment and in food, on the development of disease associated with mast cell activation must be considered. This review endeavours to outline what is known about the possible influence of sex hormones in the expression of urticaria.

Introduction

Urticaria is a common clinical disorder, pathophysiology based on mediators release from mast cells, predominantly histamine and subsequently an inflammatory response [1]. However, in most cases, aetiology of chronic urticaria is unknown; it is referred to as chronic idiopathic urticaria and in over one-third of cases the autoimmune pathogenic mechanism is proposed [2], [3]. Interestingly, altered functions of the neuro-endocrine-immune system due to stress and other factors seem to appear as a very interesting theory for urticaria pathogenesis [4]. Changes in hormones balance and expression may promote the immunological imbalance and skin function responsible for urticaria expression. For example, rare association between primary hyperparathyroidism and chronic urticaria has been described [5]. The association between chronic urticaria and autoimmune thyroiditis is frequent. l-Thyroxine reduces the symptoms of chronic urticaria associated with autoimmune thyroiditis (hypothyroid and euthyroid), suggesting a stimulatory effect of TSH able to produce considerable changes of the immune response and immune tolerance in such patients [6]. Higher expression of corticotropin-releasing hormone receptor-1 in the skin of chronic urticaria patients has been demonstrated [7]. It is known that urticaria may be associated with some diseases and/or triggered by some conditions characterized by sex hormone changes, including menstrual cycle, pregnancy, menopause, and hormonal contraceptives or hormone replacement therapy. However, the role of endogenous and exogenous sex hormones as well as estrogen mimetics in the disease pathogenesis are poorly understood.

Sex hormones are considered to be responsible for gender and menstrual cycle phase-associated differential susceptibility and severity of some immune-mediated and inflammatory diseases, including asthma, atopic dermatitis, and lupus [8], [9], [10], [11].

It is well known that fluctuations in sex hormone level associated with menstrual cycle, pregnancy, menopause and hormone administration can induce oedematous attacks in hereditary angioneurotic oedema (HANO) [12], [13], [14], [15]. Thus, it is important to consider also the possibility of the influence of sex hormones on chronic urticaria expression.

Chronic urticaria occurs approximately twice more frequently in women as compared to men [16], [17], suggesting that sex differences in hormonal milieu may play a role in this phenomenon.