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      Gestational Dermatosis Shortly after Implantation Associated with Parental Class II HLA Compatibility and Maternal Immune Activation: Preliminary Report of a Prospective Case Series

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          Abstract

          Background: Pregnancy represents a semiallograft, subject to similar immune responses as allogeneic organ transplants. Tolerance of pregnancy appears best with maximal class II HLA heterogeneity between mother and father, while compatibilities are associated with increased pregnancy loss and maternal autoimmunity. Tolerance abnormalities often involve skin reactions. Abnormalities in tolerance of the fetal graft may do the same. Objective: To define the characteristics of a newly described dermatosis in very early pregnancy. Methods: Prospective case series of 7 couples/12 clinical episodes. Results: The dermatosis was observed in 7 out of 285 women undergoing in vitro fertilization (IVF; 2.5%; 95% CI 0.66–4.26%) and in 12 out of 277 total IVF cycles reaching embryo transfer (4.3%; 95% CI 1.93–6.73%). Prior to IVF all women reported autoimmune clinically significant allergies. All but 1 couple demonstrated class II HLA compatibility. Two of 4 pregnancies miscarried. All rashes erupted within days from embryo implantation. Conclusions: The ‘implantation rash’ reported here is uncommon but not rare. It may be the consequence of abnormal maternal immune responses to embryo implantation in women with prior immune activation, associated with class II HLA compatibility between parents. Further prospective studies are required to better define this condition.

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          Most cited references13

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          Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function.

          We assessed the role of DHEA supplementation on pregnancy rates in women with diminished ovarian function. This is a case control study of 190 women with diminished ovarian function. The study group includes 89 patients who used supplementation with 75 mg daily of oral, micronized DHEA for up to 4 months prior to entry into in vitro fertilization (IVF). The control group is composed of 101 couples who received infertility treatment, but did not use DHEA. The primary outcome was clinical pregnancy after the patient's initial visit. We developed a Cox proportional hazards model to compare the proportional hazards of pregnancy among women using DHEA with the controls group. Cumulative clinical pregnancy rates were significantly higher in the study group (25 pregnancies; 28.4% vs. 11 pregnancies; 11.9%; relative hazard of pregnancy in study group (HR 3.8; 95% CI 1.2-11.8; p < 0.05). DHEA treatment resulted in significantly higher cumulative pregnancy rates. These data support a beneficial effect of DHEA supplementation among women with diminished ovarian function.
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            Value of skin biopsies in assessing prognosis and progression of acute graft-versus-host disease.

            Skin biopsies are commonly performed after allogeneic bone marrow transplantation (BMT) to help establish the origin of a new skin rash in a transplant recipient. Histologic criteria and a grading system for acute graft-versus-host reaction of the skin are well established. Histologic diagnosis, however, can be difficult and is based on interpretation of subtle changes that show significant overlap with features seen in other entities that can be responsible for a skin rash in the posttransplantation period such as drug reactions, viral exanthems, and the effects of chemotherapy. We retrospectively reviewed 179 skin biopsies from 137 patients who had undergone allogeneic BMT. We compared 98 skin biopsies from 71 patients with acute graft-versus-host disease (GvHD) with 81 biopsies from 66 patients who underwent biopsy to exclude GvHD but did not go on to develop the disease on clinical grounds. Two observers reviewed each slide without knowledge of the clinical situation and graded 16 histologic parameters. No single parameter (e.g., dyskeratotic keratinocytes, basal vacuolization, satellitosis, necrotic cells in appendages) achieved statistical significance on univariate analysis. A search for factors to separate GvHD biopsies from non-GvHD biopsies using logistic regression failed to reveal a single best predictor or a combination of predictors. We conclude that skin biopsies after allogeneic BMT are of limited use in predicting the progression of a skin rash to clinical grade II or higher GvHD.
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              Is Open Access

              FMR1 Genotype with Autoimmunity-Associated Polycystic Ovary-Like Phenotype and Decreased Pregnancy Chance

              The FMR1 gene partially appears to control ovarian reserve, with a specific ovarian sub-genotype statistically associated with a polycystic ovary (PCO)- like phenotype. Some forms of PCO have been associated with autoimmunity. We, therefore, investigated in multiple regression analyses associations of ovary-specific FMR1 genotypes with autoimmunity and pregnancy chances (with in vitro fertilization, IVF) in 339 consecutive infertile women (455 IVF cycles), 75 with PCO-like phenotype, adjusted for age, race/ethnicity, medication dosage and number of oocytes retrieved. Patients included 183 (54.0%) with normal (norm) and 156 (46%) with heterozygous (het) FMR1 genotypes; 133 (39.2%) demonstrated laboratory evidence of autoimmunity: 51.1% of het-norm/low, 38.3% of norm and 24.2% het-norm/high genotype and sub-genotypes demonstrated autoimmunity (p = 0.003). Prevalence of autoimmunity increased further in PCO-like phenotype patients with het-norm/low genotype (83.3%), remained unchanged with norm (34.0%) and decreased in het-norm/high women (10.0%; P<0.0001). Pregnancy rates were significantly higher with norm (38.6%) than het-norm/low (22.2%, p = 0.001). FMR1 sub-genotype het-norm/low is strongly associated with autoimmunity and decreased pregnancy chances in IVF, reaffirming the importance of the distal long arm of the X chromosome (FMR1 maps at Xq27.3) for autoimmunity, ovarian function and, likely, pregnancy chance with IVF.
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                Author and article information

                Journal
                DRM
                Dermatology
                10.1159/issn.1018-8665
                Dermatology
                S. Karger AG
                1018-8665
                1421-9832
                2011
                June 2011
                04 May 2011
                : 222
                : 3
                : 206-211
                Affiliations
                aCenter for Human Reproduction – New York and Foundation for Reproductive Medicine, New York, N.Y., bDepartments of Epidemiology and Social Medicine as well as Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, N.Y., and cDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Conn., USA
                Author notes
                *Norbert Gleicher, Center for Human Reproduction, 21 East 69th Street, New York, NY 10021 (USA), Tel. +1 212 994 4400, E-Mail ngleicher@thechr.com
                Article
                327377 Dermatology 2011;222:206–211
                10.1159/000327377
                21546763
                f0e95e8f-6daa-44ea-8afb-a6cfeda45ca6
                © 2011 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
                : 26 December 2010
                : 09 March 2011
                Page count
                Figures: 1, Tables: 3, Pages: 6
                Categories
                Case Report

                Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Autoimmunity,Immune activation,Skin rash,Implantation rash,Infertility,Pregnancy,Dermatosis of pregnancy,Histocompatibility antigens

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