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      Androgen Receptor Levels of Oral and Genital Ulcers and Skin Pathergy Test in Patients with Behçet’s Disease

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          Abstract

          Background: Hormonal factors have long been proposed to play a role in Behçet’s disease (BD). Male sex, systemic onset, HLA-B51 positivity and a younger age of onset in BD are associated with severer disease, and the disease generally runs a milder course in women. Vascular involvement is more common, and the skin pathergy test (SPT) is more strongly positive in men. BD rarely develops before puberty or after the age of 50 years. Clinical manifestations of the disease, with the exception of eye symptoms, tend to improve with time. Therefore, BD may be androgen driven to some degree. Objectives: We aimed to investigate androgen receptor (AR) levels of oral ulcers (OU), genital ulcers (GU) and SPT areas and compared them with those of adjacent normal-appearing skin/mucosa from patients with BD. Methods: Thirty-eight patients with BD (16 female, 22 male; mean ± SD age, 36.45 ± 10.2 years), diagnosed according to the criteria of the International Study Group for Behçet’s Disease, were included in the study with blind histological examination. Biopsies from OU of 10 patients, GU of 11 patients, SPT areas of 17 patients and adjacent (approximately 2 cm distant) normal-appearing skin/mucosa in patients with BD were performed. Nuclear AR levels were studied by an immunohistochemical technique, using monoclonal antibodies. The percentage of positively staining cells was recorded as the AR index (ARI). In addition, the prevalence and the positivity rate of SPT has also been evaluated. Results: ARI values in the lesional and control (non-lesional adjacent) skin/mucosa were found to be 14.5 versus 18% for OU, 28.7 versus 25.5% for GU and 36.3 versus 21.8% (p = 0.068) for SPT areas. The positive SPT areas in male patients showed a higher ARI than those of female patients (43.36 and 23.33%; p = 0.078). The ARI values of SPT areas in male patients but not in female patients were found to be significantly higher as compared with non-lesional skin (21.63%; p = 0.039). The SPT positivity was also more common in male patients compared with female patients (86.4% and 62.5%), although the difference was not significant (p = 0.88). SPT have been found to be more strongly positive among the males (4.63 ± 3.3) compared with female patients (3.18 ± 1.9), and the difference was statistically significant (p = 0.022). Conclusions: Our findings indicate that androgens seem to play a role both in the formation and increased positivity of the SPT areas in male patients with BD.

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          Most cited references5

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          Influence of age of onset and patient's sex on the prevalence and severity of manifestations of Behçet's syndrome.

          Eye disease, arthritis, folliculitis, and thrombophlebitis were more common among males, and erythema nodosum among females, in 297 patients with Behćet syndrome (BS) at their first visit despite an identical disease duration. Younger males and females (age of onset 24 years or less) had a higher prevalence of eye disease and total clinical activity than did the older patients (age of onset 25 years or more). Among the 51 patients followed up for 52 months (SD 7 months) the total clinical activity became significantly less (p less than 0.05) in the whole group at the end of this period. This was particularly true for older females. While male sex and a younger age of onset are associated with more severe disease in BS, overall, the syndrome ran an improving or stable course over 4 1/2 years.
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            Comparative study of the skin pathergy test with blunt and sharp needles in Behçet's disease: confirmed specificity but decreased sensitivity with sharp needles.

            To compare the specificity and sensitivity of the skin pathergy test performed with blunt and sharp needles in patients with Behçet's disease. The skin pathergy test was performed using the simultaneous four needle prick method with blunt and sharp, thick and thin needles in 92 patients with Behçet's disease, 64 healthy controls, and 128 patients without Behçet's disease. The test was evaluated at 48 hours. No positive skin pathergy test was found in healthy controls and patients without Behçet's disease. The frequency and intensity of the positive skin pathergy test with blunt needles were significantly higher than those with sharp needles. This study reconfirmed the specificity of a positive skin pathergy test for Behçet's disease using blunt and sharp needles and showed a decreased sensitivity and intensity of the reaction with sharp needles.
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              Serum of Patients with Behçet’s Disease Induces Classical (Pro-Inflammatory) Activation of Human Macrophages in vitro

              Background: Although several immunological abnormalities have been demonstrated in Behçet’s disease (BD), the exact mechanism of the inflammatory changes occurring is still unknown. Antigen-presenting cells, such as mononuclear phagocytes, play a major role in the regulation of immune-mediated as well as of non-specific inflammation. Objective: To investigate the serum activity of patients with BD on antigen and chemokine expression of human macrophages in vitro. Methods: Serum of 15 patients (8 women, 7 men; mean age 33 ± 10 years) with BD was incubated with cultured macrophages isolated from peripheral blood of healthy volunteers. Macrophages maintained in patients’ serum, fetal calf serum with/without dexamethasone and interleukin (IL)-4 or γ-interferon were investigated for alternative macrophage-activation-associated CC-chemokine 1 (AMAC-1) and IL-8 mRNA expression by Northern blotting. In addition, cytocentrifuge macrophage preparations were stained with monoclonal antibodies against proteins indicating alternative (anti-inflammatory) macrophage activation, such as MS-1 high-molecular-weight protein (MS-1-HMWP), RM3/1 antigen (CD163) and 25F9, as well as classical (pro-inflammatory) macrophage activation, such as CD11c, class I receptor binding the Fc part of IgG (FcγRI: CD64) and class III receptor binding the Fc part of IgG (FcγRIII: CD16). Results: Macrophages treated with patients’ serum showed neither AMAC-1 expression nor staining with monoclonal antibodies for MS-1-HMWP, CD163 or 25F9. Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163. In contrast, IL-8 mRNA expression and staining for CD11c and CD64 were strongly positive after treatment with serum of patients with BD. CD64 positivity and IL-8 mRNA expression were more prominent in patients with active BD than in patients with inactive disease. Conclusion: Taken together, our results indicate that serum of patients with BD induces classical (pro-inflammatory) activation of human peripheral blood macrophages in vitro. Our findings suggest that serum factor(s) may be responsible for inflammatory changes in BD.
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                Author and article information

                Journal
                DRM
                Dermatology
                10.1159/issn.1018-8665
                Dermatology
                S. Karger AG
                1018-8665
                1421-9832
                2005
                December 2004
                28 January 2005
                : 210
                : 1
                : 31-35
                Affiliations
                Departments of aDermatology and bPathology, Akdeniz University School of Medicine, Antalya, cDepartment of Dermatology, Cukurova University School of Medicine, Adana, and dDepartmentofDermatology, AtaturkUniversity School of Medicine, Erzurum, Turkey
                Article
                81480 Dermatology 2005;210:31–35
                10.1159/000081480
                15604542
                719fa891-bb38-45c9-ada4-748946bad1d3
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 04 March 2004
                : 16 August 2004
                Page count
                Figures: 2, Tables: 2, References: 14, Pages: 5
                Categories
                Clinical and Laboratory Investigations

                Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Androgen,Skin pathergy test,Behçet’s disease,Aetiopathogenesis

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