Development and multicenter international validation of a diagnostic tool to differentiate between pemphigoid gestationis and polymorphic eruption of pregnancy.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) may be similar morphologically but confer different maternal and fetal risks. Direct immunofluorescence is the gold standard test used to differentiate between the 2 diagnoses but is not always available. OBJECTIVE: To develop and validate a clinical scoring system to differentiate PG from PEP. METHODS: After developing a scoring system based on differentiating clinical factors reported in existing literature, we tested its diagnostic accuracy in a retrospective international multicenter validation study in collaboration with the European Academy of Dermatology and Venereology's Skin Diseases in Pregnancy Taskforce. RESULTS: Nineteen pregnancies (16 patients) affected by PG and 39 pregnancies (39 patients) affected by PEP met inclusion criteria. PG had a mean score of 4.6 (SD, 2.5) and PEP had a mean score of -0.3 (SD, 2.0). The area under the curve was 0.93 (95% CI, 0.86-1.00). Univariate analysis revealed that almost all criteria used in the scoring system were significantly different between the groups (P < .05), except for skip pregnancy and multiple gestations, which were then removed from the final scoring system. LIMITATIONS: Small retrospective study. CONCLUSION: The Pregnancy Dermatoses Clinical Scoring System may be useful to differentiate PG from PEP in resource-limited settings.

Anti-BP180 IgG antibody ELISA values correlate with adverse pregnancy outcomes in pemphigoid gestationis.

BACKGROUND: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet. OBJECTIVES: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis. METHODS: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres. INCLUSION CRITERIA: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available. RESULTS: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2). CONCLUSION: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG.

Histopathological features of pemphigoid gestationis and polymorphic eruption of pregnancy: A blinded retrospective comparative study of 31 cases.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) are pregnancy-related dermatoses. Definitive diagnosis often relies upon histopathology and direct immunofluorescence (DIF). PG is associated with fetal and neonatal risks, while PEP confers minimal risk. OBJECTIVE: We aimed to compare histopathologic features to determine key differentiators. METHODS: A retrospective cohort study of PG and PEP cases, with accompanying DIF, conducted from 1995 to 2020. Skin biopsies were examined independently in a blinded fashion by two dermatopathologists for a list of histopathological features. RESULTS: Twenty-one cases of PG and 10 cases of PEP were identified. PG had significantly denser eosinophils than PEP (mean 155 vs. 48 cells/5 hpf; p < 0.018). PG was also noted to have eosinophilic spongiosis and eosinophils at the dermal-epidermal junction more frequently compared to PEP (80% PG vs. 10% PEP; p < 0.001). A mean cutoff value of 86 eosinophils and a mean optimal sensitivity and specificity of 81% and 83%, respectively, for eosinophils density's diagnostic power of PEP versus PG were achieved. Subepithelial separation was exclusively seen in PG (40% vs. 0%; p < 0.007). CONCLUSION: Eosinophilic spongiosis, eosinophilic epitheliotropism, and dense superficial dermal eosinophils were diagnostic of PG. Given overlapping clinicopathologic features, however, DIF results with clinicopathologic correlation, remain the gold standard.

Recognizing, Diagnosing, and Managing Pregnancy Dermatoses.

Pregnancy dermatoses are inflammatory skin disorders that occur during pregnancy or immediately postpartum. This heterogenous group of disorders includes pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, atopic eruption of pregnancy, and pustular psoriasis of pregnancy. In this article, we provide a comprehensive literature review of each condition focusing on nomenclature, epidemiology, pathogenesis, clinical presentation, diagnosis, differential diagnosis, maternal risk, fetal risk, and treatment. We aim to increase awareness and help clinicians recognize, diagnose, and manage these unique conditions.

Pemphigoid Gestationis and adverse pregnancy outcomes: A literature review.

Pemphigoid gestationis (PG), also known as gestational pemphigoid, as it is specifically associated with a pregnancy event, is among the rare pregnancy-related dermatoses, characterised by the formation of autoantibodies against Bullous Pemphigoid antigens 180 and 230 (BP180 and BP230), causing significant damage to the basement membrane of the skin, resulting in marked pruritus and blisters on the abdomen and extremities. Diagnosis of PG is basically made by the characteristic clinical picture and confirmed by immunofluorescence studies and histopathology of a skin biopsy. Treatment, just as for other autoimmune dermatoses, is achieved by corticosteroids with the risk of relapses in subsequent pregnancies. Fetal growth restriction and pre-maturity are potential fetal complications associated with the disease, hence the recommended combined antenatal care by a dermatologist as well as an obstetrician, however, this disease is unlikely to be a source of significant maternal morbidity or mortality.

[Skin and pregnancy]. / Peau et grossesse.

Pregnancy has a substantial impact on the hormonal status of the organism, consequently influencing the physiology of the skin. This results in dermatoses that only occur during pregnancy, which can also improve or exacerbate pre-existing dermatoses. In this article, we explain the management of pregnancy-specific dermatoses : atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis, impetigo herpetiformis, and intrahepatic cholestasis of pregnancy. It is essential to clearly distinguish these different dermatoses as some of them, such as pemphigoid gestationis, impetigo herpetiformis and intrahepatic cholestasis of pregnancy, can have fetal consequences and as result, need to be closely monitored by the obstetricians.

La grossesse a un impact considérable sur le statut hormonal de l'organisme, influençant ainsi la physiologie cutanée. Cela se traduit par des dermatoses qui ne se manifestent que pendant la grossesse. Cette dernière peut également améliorer ou exacerber des dermatoses préexistantes. Dans cet article, nous précisons la prise en charge des dermatoses spécifiques de la grossesse : l'eczéma atopique de la grossesse, l'éruption polymorphe gravidique, la pemphigoïde gestationnelle, l'impétigo herpétiforme et la cholestase intrahépatique gravidique. Il est important de distinguer ces dermatoses, puisque la pemphigoïde gestationnelle, l'impétigo herpétiforme et la cholestase intrahépatique gravidique présentent un risque fœtal et par conséquence nécessitent un suivi obstétrical rapproché.

Pruritus in Pregnancy.

Pruritus in pregnancy is a common and burdensome symptom that may be a first sign of a pregnancy-specific pruritic disease (atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis, and intrahepatic cholestasis in pregnancy) or a dermatosis coinciding with pregnancy by chance. Despite its high prevalence, pruritus is often underrated by physicians, and data regarding the safety profiles of drugs for pruritus are very limited. In this review, we illustrate the epidemiology, possible pathophysiology, clinical characteristics, and diagnostic workup of various pregnancy-related diseases and discuss antipruritic treatments. The prevalence of pruritus in pregnancy demonstrates the importance of symptom recognition and the need for an holistic approach, taking into account both the potential benefits for the patient and the potential risks to the fetus.

Assessment and management of itchy skin in pregnancy.

BACKGROUND: Women with rashes or itchy skin during pregnancy will often present initially to the general practitioner. Knowledge of the specific dermatoses of pregnancy will assist in diagnosis, management and, importantly, facilitation of timely escalation of care of conditions that can potentially affect the fetus. OBJECTIVE: The aim of this article is to provide a diagnostic framework for approaching a pruritic rash during pregnancy as well as a helpful summary of management of pregnancy-specific dermatoses. It will assist clinicians in the identification of specific dermatoses that pose fetal risks. DISCUSSION: In addition to considering non-pregnancy specific conditions when approaching pruritus or a pruritic rash in pregnancy, it is important that clinicians also consider pregnancy-specific dermatoses, which have been reclassified into four categories: polymorphic eruption of pregnancy, pemphigoid gestationis, intrahepatic cholestasis of pregnancy (ICP) and atopic eruption of pregnancy. Unlike the other dermatoses, ICP begins with pruritus, and skin changes are secondary. ICP and pemphigoid gestationis are associated with fetal risks such as prematurity and stillbirth.

Neonatal pemphigoid gestationis: An atypical presentation of a rare disease.

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by urticarial plaques and/or vesicles and tense bullae. A unique presentation of BP can occur during pregnancy, the postpartum period after delivery, or with the initiation of contraception, in which case it is referred to as pemphigoid gestationis (PG). In rare instances, newborns born to mothers with PG may also present with blisters due to transplacental passage of maternal anti-bullous pemphigoid 180 (BP180) or 230 (BP230) immunoglobulin G (IgG). In this report, we present an unusual case of neonatal PG in an infant born to an asymptomatic mother without a previous diagnosis of PG.

Subepithelial autoimmune blistering dermatoses: Clinical features and diagnosis.

Subepithelial autoimmune blistering dermatoses are a group of rare skin disorders that are characterized by the disruption of the dermal-epidermal junction through the action of autoantibodies. The third article in this continuing medical education series explores the background, epidemiology, clinical features, and diagnostic criteria of each of the major subepithelial autoimmune blistering dermatoses, including bullous pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, mucous membrane pemphigoid, linear IgA bullous dermatosis, and dermatitis herpetiformis.

Pemphigoid gestationis: a rare pregnancy dermatosis treated with a combination of IVIg and rituximab.

Pemphigoid gestationis is a rare autoimmune subepidermal bullous dermatosis occurring during pregnancy and post partum. A 32-year-old woman developed itchy urticarial wheals over the trunk and extremities at 6 months of gestation. This was not controlled with antihistamines, and 2 months later, the patient developed multiple vesiculobullous lesions. The patient had an exacerbation 3 weeks post-delivery. She did not go into remission for 6 months post partum despite treatment with prednisolone 40 mg/day, doxycycline 100 mg two times per day and dapsone 100 mg/day. The patient went into remission following treatment with three courses of intravenous immunoglobulin 2 mg/kg/course and 2 doses of rituximab 1 g at a 2-week interval.