Pemphigoid gestationis (PG) (previously called herpes gestationis) is a rare, specific dermatosis of pregnancy. It is a bullous autoimmune, sub-epidermal dermatosis clinically and pathogenetically similar to bullous pemphigoid. It occurs during the third trimester and less commonly in the second trimester or even after delivery, but it can manifest in principle during all three trimesters. It manifests with inflammatory skin lesions and severe pruritus. It recurs in subsequent pregnancies earlier and as a more serious course.
In PG, the skin lesions are caused by an autoimmune process implicated anti-basement membrane zone auto-antibodies. The target autoantigen is BP 180 also designated BPAG2 and collagen XVII. PG is strongly associated with the maternal HLA-DRs DRB1*0301 (HLA-DR3) and DRB1*0401/040X (HLA-DR4). This strong association indicates the important role of MHC class II in the pathogenesis of the disease.
The incidence of PG has been variably estimated, one case per 2000 up to 60,000 pregnancies. It is more frequent in persons with fair skin than dark skin. PG mainly occurs late in pregnancy with 60% of cases occurring between the 28th and the 32nd week of amenorrhea. Multigravidae are more susceptible to develop PG than primigravidae with an earlier onset of symptoms.
PG usually resolves within 2 months after delivery. Nonetheless, it may persist or exacerbate after pregnancy due to a sudden increase in the level of antibodies. Recurrence may occur with subsequent pregnancies, menstruations or treatment with estrogens and progesterone-containing oral contraceptives. Fetal risks observed in PG are low birth weight baby, prematurity, and temporary skin lesions which resolve several weeks after the birth, but there is no increased risk of stillbirth and abortion. This risk may be correlated with disease severity. A postpartum flare-up has been observed.
The association of this disease with hydatidiform mole and choriocarcinoma must not be forgotten.
PG is associated with the presence of IgG autoantibodies against BP180, which predominantly recognize the NC16A domain of BP180. BP180 is not only expressed in the skin, but also in the first trimester of pregnancy in the placental cytotrophoblastic and syncytiotrophoblastic cells as well as in the epithelial cells of the amniotic membrane. Autoimmunization may occur due to loss of tolerance to this 180 kDa placental antigen, resulting in a local allogeneic reaction against the fetoplacental unit. This process, which is promoted by abnormal expression of placental HLA class II antigens, is accompanied by alterations in the placental basement membrane. After that, there is an immune response in the skin.
Routine histopathologic studies are helpful; the findings during examination depend on the phase of the disease. While it shows in the pre-bullous stage a papillary edema with an infiltration of the dermis, consisting of lymphocytes and histiocytes and a variable number of eosinophils, it reveals in the bullous stage subepidermal blistering, however, histology is not sufficient in the diagnosis of PG.
The eruption of PG is polymorphic. Pruritus is the main symptom, and it may precede the manifestation of skin lesions in some cases. It may be very severe and have a significant emotional impact on the patient. The eruption can include eczematous or erythema multiforme-like lesions, erythematous urticarial plaques and papules which progress to vesicles, tense blisters and bullae in over 65% of cases. At first, the lesions erupt in the periumbilical area and subsequently spread to the abdominal region and the extremities, involving exceptionally the face or mucous membranes. The lesions may extend to the entire body. There is no mucosal involvement. The clinical aspect and the distribution of skin lesions or histological examinations (almost constantly unspecific) in the initial phase cannot distinguish pemphigoid gestationis from other pruriginous dermatoses of pregnancy especially the multi-morphe eruption of pregnancy (previously nommed Polymorphic Urticarial Papules and Plaques of Pregnancy (PUPPP)) which is the main differential diagnosis. This latter also develops in the third trimester of pregnancy and exhibit similar clinical features. In pre-bullous stage, the differentiation between the two diseases is impossible, both histopathologically and clinically. However, the direct immunofluorescence is negative in this case.
Direct immunofluorescence (DIF) staining on skin biopsy specimen should be realized because it is considered the most sensitive and specific examination used for confirming the diagnosis. It confirms the diagnosis by showing positive linear C in 100% of the cases, and occasionally IgG in 30%, depositions along the dermal-epidermal junction of lesional, perilesional and clinically normal skin. DIF sometimes remains positive even for six months to 4 years after clinical remission.
ELISA-BP180 is very sensitive and specific (approximately 95%) for the diagnosis of pemphigoid gestationis. His positivity would allow to differentiate GP from other pruriginous dermatoses of pregnancy reliably and to potentially render obsolete the practice of a direct immunofluorescence test, which nevertheless remains the reference standard.
Its positivity would make it possible to reliably distinguish pemphigoid gravidarum from other pruriginous dermatoses of the pregnancy, and potentially make obsolete the practice of a direct immunofluorescence examination, which nevertheless remains still the reference standard. The result of the ELISA-BP180 is semi-quantitative, and its evolution correlates with the activity of the disease.
Treatment of PG depends on the severity and the stage of the skin lesions. The main goal is to relieve itching and to avoid the formation of new blisters.
PG is a rare disease and does not pose a major health burden. When suspected clinically, the diagnosis must be established, and treatment should be started early as the disease responds well to steroids. A an interprofessional approach between gynecologist and dermatologist is required to ensure coordinated monitoring (search for signs of prematurity, abnormalities of fetal growth, detect possible systemic and local side effects of topical and systemic corticosteroid). The association with hydatiform mole, trophoblastic tumors, or choriocarcinoma must not be forgotten. The pharmacist should encourage medication compliance to help ease the intense pruritus.
We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.
This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.
|Pruritus in Pregnancy and Its Management., Bechtel MA,, Dermatologic clinics, 2018 Jul [PubMed]|
|Daniel BS,Murrell DF, Review of Autoimmune Blistering Diseases: the Pemphigoid diseases. Journal of the European Academy of Dermatology and Venereology : JEADV. 2019 May 13; [PubMed]|
|Kukkamalla RM,Bayless P, Pemphigoid Gestationis. Clinical practice and cases in emergency medicine. 2019 Feb; [PubMed]|
|Lobato-Berezo A,Fernández Figueras MT,Moreno Romero JA,Pujol RM, Pemphigoid Gestationis Mimicking Erythema Multiforme With Mucosal Involvement. Actas dermo-sifiliograficas. 2019 Feb 4; [PubMed]|
|Maglie R,Quintarelli L,Verdelli A,Fabbri P,Antiga E,Caproni M, Specific dermatoses of pregnancy other than pemphigoid gestationis. Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2019 Jun; [PubMed]|
|Feliciani C,Genovese G,D'astolto R,Pontini P,Marzano AV, Autoimmune bullous diseases during pregnancy: insight into pathogenetic mechanisms and clinical features. Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2019 Jun; [PubMed]|
|Papapanagiotou IK,Tsagouri S,Liakou CG,Besharat A,Vogiatzis N,Ntzeros K,Petrakis E,Koutroumanis P,Thomakos N,Loutradis D, Pemphigoid gestationis. Clinical case reports. 2018 Jul; [PubMed]|
|Yang A,Uhlenhake E,Murrell DF, Pemphigoid gestationis and intravenous immunoglobulin therapy. International journal of women's dermatology. 2018 Sep; [PubMed]|
The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Rheumatology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.
StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Rheumatology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Rheumatology, you will already be prepared.
Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Rheumatology. When it is time for the Rheumatology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Rheumatology.