Journal name: Clinical, Cosmetic and Investigational Dermatology Article Designation: REVIEW Year: 2017 Volume: 10 Clinical, Cosmetic and Investigational Dermatology Dovepress Running head verso: Sävervall et al Running head recto: Pemphigoid gestationis open access to scientific and medical research DOI: http://dx.doi.org/10.2147/CCID.S128144 Open Access Full Text Article REVIEW Pemphigoid gestationis: current perspectives Christine Sävervall1 Abstract: Many skin diseases can occur in pregnant women. However, a few pruritic derma- Freja Lærke Sand1 tological conditions are unique to pregnancy, including pemphigoid gestationis (PG). As PG Simon Francis Thomsen1,2 is associated with severe morbidity for pregnant women and carries fetal risks, it is important for the clinician to quickly recognize this disease and refer it for dermatological evaluation and 1Department of Dermatology, Bispebjerg Hospital, Copenhagen, treatment. Herein, we review the pathogenesis, clinical characteristics, and management of PG. Denmark; 2Department of Biomedical Keywords: pemphigoid gestationis, pregnancy, skin diseases Sciences, University of Copenhagen, Copenhagen, Denmark Introduction Skin changes are common during pregnancy and can be divided into benign physi- For personal use only. ologic skin changes due to normal hormonal/physiological changes,1 alterations in preexisting skin diseases because of immunohormonal changes, and pregnancy-specific dermatoses. Pregnancy-specific dermatoses represent a group of skin diseases that occur only during pregnancy and/or the immediate postpartum period. Severe pruritus represents the leading symptom commonly followed by a more widespread skin rash. Pregnancy-specific dermatoses include: pemphigoid gestationis (PG), polymorphic eruption of pregnancy (PEP), intrahepatic cholestasis of pregnancy (ICP), and atopic eruption of pregnancy (AEP).2 PG or gestational pemphigoid is a rare pregnancy-associated autoimmune skin disorder that is immunologically and clinically similar to the pemphigoid group of autoimmune blistering skin disorders. The pathogenesis is not yet fully established, but it belongs to the group of autoimmune skin disorders characterized by an immune response directed against different hemidesmosomal proteins affecting the adher- Clinical, Cosmetic and Investigational Dermatology downloaded from https://www.dovepress.com/ by 137.108.70.13 on 23-Jan-2020 ence between the dermis and epidermis causing blistering of the skin and mucosal membranes.3 Clinically, PG is characterized by intense pruritus and polymorphic skin eruptions. Pruritus can emerge before skin lesions and remain the only symptom. In more severe cases, skin lesions develop including erythematous patches and plaques, sometimes followed by urticarial rash and blisters. PG was previously termed herpes gestationis because the morphology of the blisters was similar to that of herpes, but Correspondence: Simon Francis Thomsen it was shown not to be related to, or associated with, any prior or active herpes virus Department of Dermatology, Bispebjerg infection. Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark Some pregnancy-specific dermatoses carry considerable morbidity for pregnant Tel +45 3863 5844 women and can pose a significant risk to the fetus, such as premature birth and Fax +45 3863 9785 4 Email [email protected] small-for-gestational age babies. It is therefore important to recognize and separate submit your manuscript | www.dovepress.com Clinical, Cosmetic and Investigational Dermatology 2017:10 441–449 441 Dovepress © 2017 Sävervall et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work http://dx.doi.org/10.2147/CCID.S128144 you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Sävervall et al Dovepress these diseases from other benign pregnancy-associated skin occur is still unknown. Both primiparous and multiparous changes. Pregnant women who present with a pruritic rash women are affected, but most cases are reported to occur should always get immediate clinical evaluation, and if neces- in multiparous women,11,14,19 although this is not congruent sary referred to a dermatologist. In this review, we elucidate with a study of 23 cases where 56.5% of the women with PG the epidemiology, pathogenesis, clinical characteristics, were primiparous.15 There is no association between change treatment, and complications of PG. in partner and development of PG,14 which was previously suggested.22 Epidemiology and risk factors General population studies on the epidemiology of PG are Pathogenesis rare. Population-based studies have reported an annual inci- The pathogenesis of PG is considered to be similar to that dence ranging between 0.5 and 2.0 cases per 1 million people of bullous pemphigoid, which is characterized by deposition in France, Kuwait, Iran, and Germany.5–8 The incidence is of autoreactive antibodies directed against two hemidesmo- estimated to be approximately 1 in 60,000 pregnancies.9,10 somal proteins, BP180 and BP230, within the dermoepider- The disease shows a worldwide distribution2,5,6,8,11,12 and no mal junction, resulting in the formation of bullae and skin differences in ethnicity.13 The median age of affected women erosions.23 In PG, the first immune response occurs within varies between 17 and 41 years, with a median age of onset the placenta. Placental trophoblasts and amniochorionic around 26–32 years.11,14–16 stromal cells show an abnormal expression of major histo- PG mainly affects multiparous women in their second or compatibility complex (MHC) class II antigens24 allowing third trimester of pregnancy, but onset in the first trimester or the presentation of BP180 (also known as BPAG1 or collagen postpartum period is also reported.2,11,12,14,16–19 In a case series XVII) protein to the maternal immune system. BP180 is a from the UK of women with PG including 117 pregnancies, key structural protein of hemidesmosomes linking the epi- the time of onset of PG ranged from 5 weeks of gestation to dermis and dermis.25 BP180 is found in placental tissue, in 35 days postpartum. Of the 117 pregnancies, 21 (17.9%) pre- fetal membranes, and also in the basement membrane zone For personal use only. sented in the first trimester, 40 (34.2%) presented in the sec- of the skin. These specific proteins presented in the placenta ond trimester, and 40 (14.2%) presented in the third trimester, are recognized as foreign, causing subsequent production of whereas in 16 (13.7%) the eruption began postpartum.14 In anti-placental IgG antibodies that cross-react with the same another case series from Austria including 21 pregnancies, BP180 proteins in the skin. The binding of these antibodies to 15 (71%) had onset during the third trimester and 6 (29%) the basement membrane of the skin triggers an autoimmune had an onset in the second trimester.2 The tendency for response that consists of complement activation, deposi- onset late in pregnancy was also confirmed in a third study tion of immunecomplexes, consecutive chemoattraction from Saudi Arabia including 32 patients which showed that of eosinophil granulocytes, and subsequent degranulation, 84% of women had onset of PG during the second or third resulting in tissue damage and blister formation.26 trimester.11 Finally, in a smaller study from the UK including Immunogenesis is also found to play a role in the patho- 15 cases of PG, 8 women had onset in the third trimester, 2 genesis of PG. It has been delineated that PG has a strong in the immediate postpartum period, whereas 4 presented in association with maternal MHC class II antigens haplotypes the second trimester.19 HLA-DR3 and HLA-DR4.27 These haplotypes have been Clinical, Cosmetic and Investigational Dermatology downloaded from https://www.dovepress.com/ by 137.108.70.13 on 23-Jan-2020 Recurrences in subsequent pregnancies are common and shown to be more common in women with PG compared to are usually more severe and with an earlier onset.1,15,17,20 Stud- a healthy control population. The presence of MHC II-class ies show recurrences in 33%–50% of patients,11,21 but cases HLA-antigens DR3 was found in 61%–80% of patients com- of uninvolved or skipped pregnancies following a previously pared to only 22% in controls. DR4 was found in 52%–53% affected pregnancy are also reported. In a case study includ- of patients compared to 33% in controls. Notably, the combi- ing 25 patients with PG, 2 patients (8%) presented with an nation of these two haplotypes was found in 45% of patients uninvolved pregnancy following a previously affected preg- compared to 3% of controls.27,28 nancy.22 In another study of 87 patients with PG, 7 patients Fluctuations in sex hormones are also proposed to play a (8%) had an uninvolved pregnancy. This study also showed role in the pathogenesis of PG. This is due to observations of that skipped pregnancies could not be explained by a change a clinical flare or exacerbation during menstruation or follow- in sexual partner or by the mother and the fetus being fully ing administration of oral contraceptives postpartum,9,14,29,30 compatible at the DR locus.14 Why skipped pregnancies but these observations are not consistent across studies.14 442 submit your manuscript | www.dovepress.com Clinical, Cosmetic and Investigational Dermatology 2017:10 Dovepress Powered by TCPDF (www.tcpdf.org) 1 / 1 Dovepress Pemphigoid gestationis Clinical features and 3).2,11,14,19 In 90% of the cases, it later spreads to the rest of PG initially presents with intense pruritus and inflamma- the abdomen (Figure 4), and in some patients the involvement tory skin lesions (Table 1).