Report Thyrotropin receptor gene expression in the association between chronic spontaneous urticaria and Hashimoto’s thyroiditis Maria R. C. Silvares 1 , MD, PhD, Maria R. P. Fortes 1 , PhD, Renata de A. M. L. Nascimento 2 , PhD, Carlos R. Padovani 3 , PhD,H  elio A. Miot 1 , MD, PhD,C  elia R. Nogueira 2 , MD, PhD, and Gl  aucia M. F. da S. Mazeto 2 , MD, PhD 1 Department of Dermatology and Radiotherapy, Botucatu Medical School, Sao Paulo State University – Unesp, Botucatu, Sao Paulo, Brazil, 2 Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University – Unesp, Botucatu, Sao Paulo, Brazil, and 3 Department of Biostatistics, Institute of Bioscience, Sao Paulo State University – Unesp, Botucatu, Sao Paulo, Brazil Correspondence Gl aucia M. F. S. Mazeto, MD, PhD Department of Internal Medicine Botucatu Medical School, Unesp 18618-970 Botucatu Sao Paulo Brazil E-mail: gmazeto@fmb.unesp.br Conflicts of interest: The author(s) declare (s) that there is no conflict of interests regarding the publication of this paper. doi: 10.1111/ijd.13487 Abstract Background Chronic spontaneous urticaria (CSU) may be associated with autoimmune thyroid diseases, and the Autologous Serum Skin Test (ASST) is an autoreactivity marker. The thyrotropin (TSH) and TSH receptor (TSHR) could play a role in the pathogenesis of CSU. The aim of this study was to evaluate ASST positivity and TSHR gene expression in healthy skin and ASST wheals in euthyroid women with CSU, with (14 patients) and without (15 patients) Hashimoto’s thyroiditis (HT). Methods ASST was performed and TSHR gene expression studied in wheals induced by ASST and in healthy skin. Results ASST presented greater positivity (86% 9 40%) and larger diameter (10.8 9 9.6 mm) in the HT group (P < 0.05). TSHR gene expression was higher in the ASST area and healthy skin of HT group (P < 0.01). Positive correlation of antibodies levels with ASST wheal measurements and TSHR gene expression was seen. Conclusions Women with CSU and HT presented greater positivity and larger measurements for ASST and higher TSHR expression in the skin, suggesting association between CSU, thyroid autoimmunity, and TSHR. Introduction Chronic urticaria (CU), a severe and common condition, has a great impact on a patient’s quality of life. 1,2 In most cases, the cause is unknown, thus the condition is known as chronic spon- taneous urticaria (CSU). 3,4 Autoimmune phenomena are identi- fied in approximately 25–45% of CSU cases characterized by the detection of IgG class histamine releasing antibodies direc- ted against high affinity IgE receptors (antiFceRI) or against IgE itself, 3–5 and the Autologous Serum Skin Test (ASST) assesses such autoreactivity. 1,6,7 There are reports of association between CSU and autoim- mune thyroid disease, 8–10 specifically Graves disease (GD) and Hashimoto’s thyroiditis (HT). 10–12 HT is the most common autoimmune thyroid disease and may evolve to primary hypothy- roidism. Autoantigens such as thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin (TSH) receptor have been proposed to be involved in its pathogenesis. 13,14 To strengthen the link between HT and CSU, it has been observed that this dermatological condition, when associated with the autoimmune thyroid disease, responds poorly to conventional treatment, and improvements with levothyroxine use were reported in some studies. 11,15–17 These findings support the research of a new TSH role, and perhaps of its receptor, in immune response. Indeed, TSH receptor (TSHR) detection in dermis fibroblasts and melanocytes indicates that the skin is a target of thyroid axis. 18–20 Thus, both thyroid autoimmunity and hormonal action on the TSHR could be involved in the pathogenesis of CSU. However, currently, the mechanisms involved in the relationship between CSU and thy- roid disease, particularly HT, are unknown, which raises the ques- tion of whether both conditions have a cause–effect relationship or are two simultaneous autoimmune diseases. ª 2017 The International Society of Dermatology International Journal of Dermatology 2017 1