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

Polymorphic eruption of pregnancy (PEP) and herpes gestationis (HG) are pregnancy-related dermatoses of unknown aetiology with eosinophil infiltration which, at early stages, may show similar clinical and histopathological features. To determine the relative contributions of eosinophils, neutrophils and mast cells to the pathogenesis of PEP and HG through deposition of granule proteins, we studied tissue and serum from 15 patients with PEP and 10 with HG. Using indirect immunofluorescence with antibodies to human eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), neutrophil elastase and mast cell tryptase, we determined and compared cellular and extracellular staining patterns in lesional skin biopsy specimens and, using immunoassay, measured MBP, EDN, and ECP in patients' sera. Eosinophil infiltration and extracellular protein deposition of all three eosinophil granule proteins were present in both PEP and HG indicating a pathogenic role for eosinophils in both diseases. Staining for eosinophil granule proteins was especially prominent in urticarial lesions and around blisters in HG. EDN and ECP serum levels in PEP and ECP serum levels in HG were significantly increased compared with those in normal pregnant and normal nonpregnant serum. Neutrophils were more prominent in HG specimens than in PEP specimens; extracellular neutrophil elastase was minimally present and similar in both diseases. Mast cell numbers and extracellular tryptase deposition did not differ between the two diseases and did not differ from mast cell counts in skin of normal pregnant women. This study shows that eosinophil granule proteins are deposited extracellularly in tissue and are increased in serum in both PEP and HG. Moreover, eosinophil involvement in the two diseases is more consistent than neutrophil and mast cell involvement. Comparatively, tissue eosinophil infiltration and extracellular protein deposition is more extensive in HG than in PEP, suggesting that eosinophil involvement is greater in the pathogenesis of HG than PEP and similar to that found in bullous pemphigoid.

The specific dermatoses of pregnancy represent a heterogeneous group of pruritic skin diseases that have been recently reclassified and include pemphigoid (herpes) gestationis, polymorphic eruption of pregnancy (syn. pruritic urticarial papules and plaques of pregnancy), intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. They are associated with severe pruritus that should never be neglected in pregnancy but always lead to an exact work-up of the patient. Clinical characteristics, in particular timing of onset, morphology and localization of skin lesions are crucial for diagnosis which, in case of pemphigoid gestationis and intrahepatic cholestasis of pregnancy, will be confirmed by specific immunofluorescence and laboratory findings. While polymorphic and atopic eruptions of pregnancy are distressing only to the mother because of pruritus, pemphigoid gestationis may be associated with prematurity and small-for-date babies and intrahepatic cholestasis of pregnancy poses an increased risk for fetal distress, prematurity, and stillbirth. Corticosteroids and antihistamines control pemphigoid gestationis, polymorphic and atopic eruptions of pregnancy; intrahepatic cholestasis of pregnancy, in contrast, should be treated with ursodeoxycholic acid. This review will focus on the new classification of pregnancy dermatoses, discuss them in detail, and present a practical algorithm to facilitate the management of the pregnant patient with skin lesions.

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

Polymorphic eruption of pregnancy (PEP), formerly known as pruritic urticarial papules and plaques of pregnancy, is a dermatosis of pregnancy that must be distinguished from pemphigoid gestationis (PG). Although this differential diagnosis may be possible on routine histology, an additional biopsy for direct immunofluorescence (DIF) is often needed. Recent studies have demonstrated the utility of anti-C4d or anti-C3d antibodies in the diagnosis of bullous pemphigoid (BP) in formalin-fixed paraffin-embedded tissue (FFPE). We investigated the utility of routine immunohistochemistry (IHC) for anti-C4d in FFPE tissue in the specific differential diagnosis of PEP versus PG in known, DIF-proven cases. We performed C4d IHC on PEP (n = 11), PG (n = 8), DIF-proven BP (n = 12), and other common dermatoses (n = 12) that are typically DIF negative. None of the PEP cases (0/11) or the other common dermatoses (0/12) demonstrated C4d positivity at the basement membrane zone. In comparison, 100% of PG cases (8/8) and 83.3% of BP cases (10/12) showed linear C4d immunoreactant deposition along the basement membrane zone. The results demonstrate the potential utility of C4d IHC in FFPE tissue for distinguishing PEP from PG, thus potentially obviating the need of a repeat biopsy for DIF, particularly in C4d-negative cases where there is a low suspicion of PG on both clinical and histological grounds. Also, patients with positive C4d-positive immunoreactivity may also potentially proceed directly to less invasive serological confirmatory testing, such as BP180 NC16a enzyme-linked immunoabsorbent assay.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a specific dermatosis of pregnancy common to primigravid women in the third trimester. The rash usually begins on the lower abdomen within striae and spreads to the proximal extremities. Involvement of face, palms, and soles is unusual. Although intensely pruritic, the fetus is unaffected, and the condition does not usually recur. It can be difficult to distinguish PUPPP from pemphigoid gestationis, an autoimmune bullous disorder with potential fetal consequences that may recur with subsequent pregnancy, menses, or hormonal therapy. A young secundagravida at 36 weeks of gestation with monochorionic twins presented with a 3-week history of a pruritic papular eruption that began on the abdomen and spread to the extremities. She had extensive involvement of the distal extremities, including the palmoplantar surfaces, with small vesicles of 2-4 mm on acral skin. Because of her unusual presentation, she was thought initially to have pemphigoid gestationis. Subsequent dermatological evaluation and a biopsy confirmed the diagnosis of PUPPP. Shortly after admission she delivered 2 healthy male infants, and her rash cleared with conservative management. Pruritic urticarial papules and plaques of pregnancy often, but not always, spares the face, palms, and soles. Small vesicles can occur in PUPPP, but formation of true bullae is not observed. Careful dermatological examination and cutaneous biopsy can assist in differentiating PUPPP from pemphigoid gestationis, which is essential for treatment and prognosis.

The specific dermatoses of pregnancy revisited and reclassified: Results of a retrospective two-center study on 505 pregnant patients

33841 Pregnancy dermatosis clinical scoring system: How to predict between pemphigoid gestationis and polymorphic eruption of pregnancy

Pruritic Urticarial Papules and Plaques of Pregnancy

The specific dermatoses of pregnancy represent heterogeneous group of pruritic skin disorders that occur exclusively in pregnancy. The updated classification proposed subdividing specific dermatoses of pregnancy into four main categories: 1. atopic eruption of pregnancy; 2. polymorphic eruption of pregnancy; 3. pemphigoid gestationis; 4. intrahepatic cholestasis of pregnancy. Severe pruritius, which is the main symptom in all 4 entities, can impair maternal quality of life. Significant maternal risks are not associated with specific dermatoses of pregnancy; however, pemphigoid gestationis and intrahepatic cholestasis of pregnancy are associated with fetal risks. Pathognomonic laboratory tests are not available, except direct immunofluorescence which is diagnostic of pemphigoid gestationis and elevated serum level of bile acids of intrahepatic cholestasis of pregnancy. Characteristic clinical features provide discrimination between polymorphic eruption of pregnancy and atopic eruption of pregnancy.

Aronson, Iris K.; Bond, Shirley; Fiedler, Virginia C.; Vomvouras, Stephanie; Gruber, David; Ruiz, Catherine Author Information

27 - Pregnancy Dermatoses

Specific dermatoses of pregnancy are skin disorders that occur specifically during or immediately after pregnancy and cannot be found in non-pregnant patients. According to the current consensus, they include atopic eruption of pregnancy (AEP), polymorphic eruption of pregnancy (PEP), pemphigoid gestationis (PG), and intrahepatic cholestasis of pregnancy (ICP). The diagnosis of specific dermatoses of pregnancy can be challenging due to their variation in clinical presentation; moreover, the tests currently available do not always provide the clue for the diagnosis. However, some distinctive features may be helpful to differentiate between such entities. Accordingly, the knowledge of specific dermatoses of pregnancy and of their management is critical, since their early recognition may allow to provide care for the mother and prevent potential increased fetal risk. In fact, while AEP and PEP do not affect maternal and fetal prognosis, PG and, mainly, ICP are associated to maternal complications as well as the risk of fetal loss. In this paper, the epidemiology, pathogenesis, clinical features as well as management of AEP and PEP are reviewed in detail, while PG is described in another article of this issue. Moreover, the main features of ICP, which cannot be considered a primarily skin disease but may be managed first by dermatologists, are reported.

27 - Pregnancy Dermatoses

The specific dermatoses of pregnancy represent aheterogeneous group of inflammatory skin diseases related to pregnancy and/or the postpartum period. Aclinically relevant classification has been well established over the past 10years and includes pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. The hallmark of all four entities is severe pruritus that is accompanied by characteristic skin changes. While some of these dermatoses are distressing only to the mother because of pruritus, others may be associated with significant fetal risks. Early diagnosis and prompt treatment are therefore essential. In this review, we discuss in detail pemphigoid gestationis, polymorphic and atopic eruptions of pregnancy whereas intrahepatic cholestasis of pregnancy is discussed in aseparate article (Kremer A, Ständer S, DOI 10.1007/s00105-016-3923-y ). Furthermore, we present ahelpful algorithm for diagnosis and management of pruritus in pregnancy.

Five patients with typical bullous herpes gestationis and five patients with polymorphic eruption of pregnancy were studied. Shave biopsies were taken from both involved and uninvolved skin and examined by routine immunofluorescence. They were also examined by immunoelectron microscopy employing a multistep peroxidase-antiperoxidase technique which has been shown to be more sensitive than immunofluorescence. Despite the increased sensitivity of immunoelectron microscopy all cases of polymorphic eruption of pregnancy were completely negative. Although there is a considerable clinical and histopathological overlap between herpes gestationis and polymorphic eruption of pregnancy our findings indicate that these conditions are pathogenetically distinct and should be classified as separate disorders.