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Pemphigoid Gestationis - a Rare Disease Encountered in Pregnancy

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Pemphigoid Gestationis - a Rare Disease Encountered in Pregnancy Gineco.eu[11] 138-140 [2015] DOI: 10.18643/gieu.2015.138 @ 2015 Romanian Society of Ultrasonography in Obstetrics and Gynecology Pemphigoid gestationis - a rare disease encountered in pregnancy Mircea Abstract Tampa1,2, Pemphigoid gestationis is a specific autoimmune disease of pregnancy. The onset occurs most commonly in the second Madalina or third trimester of pregnancy. Initially, the clinical picture is difficult to distinguish from polymorphic urticarial papules Mitran2, and plaques of pregnancy, urticarial plaques being present in both. Afterwards, the lesions form tense vesicles and Cristina bullae on an erythematous base. Direct immunofluorescence reveals C3 linear deposits, with or without IgG deposits Mitran2, along the basement membrane zone. Circulating antibodies are directed primarily against type XVII collagen (BP 180). 2 The main fetal risks are preterm birth and fetal growth restriction. The treatment may be harmful for the fetus. Mild Isabela Sarbu , and moderate topical corticosteroids should be used. Systemic corticotherapy, azathioprine or dapsone should be Clara Matei1, administered in severe cases. Disease activity and treatment efficacy may be evaluated by measuring antibodies titer. Vasile Benea2, Keywords: pemphigoid gestationis, pregnancy, autoimmune disease Tony Hangan3, Diana Badiu3, Dan Navolan4, Simona-Roxana Georgescu1,2 Introduction Clinical manifestations Pregnancy is a period characterized by metabolic, en- If PG is not timely recognized, the treatment may 1. “Carol Davila” University of Medicine and Pharmacy, docrinological and immunological changes that have an be inappropriate. Pruritus is a common symptom in Bucharest, Romania, impact on the skin(1). The immunosuppressant during pregnant women and is frequently attributed to other 2. “Victor Babes” Hospital for Infectious and Tropical pregnancy, needed for the tolerance of the fetus by the diseases that occur during pregnancy. The absence of Diseases, mother’s immune system, plays a role in the occurrence an early diagnosis can lead to neonatal complications Bucharest, Romania, (2) (10) 3. Faculty of Medicine, of the autoimmune diseases in pregnant women . and preterm birth . The main differential diagnosis ”Ovidius” University of Constanta, Romania, Pemphigoid gestationis (PG), was the first specific is associated with PUPPP and could be achieved using 4. Department dermatosis of pregnancy ever described. PG can be immunoblotting or enzyme-linked immunosorbent of Obstetrics-Gynecology and Neonatology, differentiated from the other dermatoses since 1973, assay (ELISA), tools based on the identification of anti- ”Victor Babes” University when immunofluorescence microscopy was develo- basement membrane zone autoantibodies(11). of Medicine and Pharmacy Timisoara, ped. The first classification of specific dermatoses of Usually the onset of lesions is periumbilical and the City Emergency pregnancy was accomplished in 1982 by Holmes et al. eruption extends to the abdomen and legs, involving Clinical Hospital Timisoara, (12) Timisoara, Romania, and included pemphigoid gestationis, polymorphic the palms and soles . In a recent study, it was found urticarial papules and plaques of pregnancy (PUPPP) that the lesions started on the legs in the majority of Correspondence: (3) (13) Mircea Tampa and prurigo of pregnancy . patients . The face and mucous membranes are rarely e-mail: tampa_mircea@ (9) yahoo.com PG is an autoimmune skin disorder, occurring more involved . However, the study conducted by Rassai frequently during the second and third trimester, but and contributors including 13 pregnant women with *All authors have equally (4,5) contributed to this work. the onset may be at any stage of the pregnancy . PG, revealed the frequent involvement of the face, PG has also been reported in puerperium period in as well as the fact that the majority of the patients Acknowledgement: (4) This paper is partly 14-20% of cases. It is a rare disease with an incidence were primiparous . In contrast, other studies have supported by the Sectorial of 1 in 50.000. However, Zurn and contributors have showed that PG commonly occurs in multiparous wo- Operational Programme (6) (14,15) Human Resources estimated an incidence of 1 in 7000, in their study . men . A study performed by Tani el al. has revealed Development (SOPHRD), financed by the European An association between PG and the presence of human that multiparous women develop PG during an earlier Social Fund and leukocyte antigen (HLA) DR3 and HLA DR4 has been stage of pregnancy than primiparous(16). Oral mucous the Romanian Government (7) (17) under the contract number observed . PG is more common in caucasian people. membrane is involved in 20% of cases . A case of PG POSDRU 141531. This could be explained by the fact that HLA DR3 that initially involved the oral mucous membrane has and HLA DR4 are found in a greater proportion in also been reported(18). these individuals(6,8). Furthermore, PG was originally PG is characterized by urticaria-like lesions consisting Received: June 19, 2015 termed herpes gestationis by John Laws Milton, in in itchy edematous plaques. Sometimes the lesions have Revised: 1872, given the herpetiform appearance of the lesions. a target-like or polycyclic aspect. Intense itching is a July 03, 2015 Accepted: Subsequently, further studies have shown that there constant complaint. Pruritus may precede the onset of August 21, 2015 is no connection between PG and herpetic infection(9). the lesions(12,19,20). Afterwards, the lesions form tense 138 Vol. 11 • No. 41 (3/2015) Tampa et al. Pemphigoid gestationis - a rare disease encountered in pregnancy gineco eu vesicles and bullae on an erythematous base. The pa- depend on the stage and severity of the disease. In the tient may develop a generalized eruption. The lesions prebullous stage, edema of the dermis and perivascular improve just before the delivery but worsen at the time inflammatory infiltrate may be observed(3,17). of delivery(9). Sometimes the lesions are reminiscent Physical examination, direct immunofluorescence of erythema multiform lesions. Several cases of PG and serology are the main steps in making the diagno- without blisters have been reported(6). The rash may sis. Direct immunofluorescence of perilesional skin be painful. The blisters may break and small ulcers represents the key in the diagnosis of PG and reveals may occur. The healing is without scarring(21). In the linear deposition of C3 along the basement membrane prebullous stage, the clinical differentiation between zone, with or without IgG deposits(6,23,25). Immunoelec- PUPPP and PG may be difficult(1). tonomicroscopy identifies immunoreactants deposits in the lamina lucida, in its upper layer(27). Circulating Pathogenesis autoantibodies may be found by indirect immunoflu- The pathogenic mechanism of PG remains unclear. orescence, in 20-60% of cases. By using complement It is based on the formation of antibodies against pla- fixation technique IgG antibodies are detected in 90% cental proteins, which are also found in the skin. The of cases(5,8). immune process starts in the placenta. Antibodies are Biopsy is not always accepted by the patient, there- particularly directed against type XVII collagen (BP180), fore additional tests are needed. Immunoblotting and a transmembrane hemidesmosomal protein which ELISA seem to be useful alternatives. These tests detect is found in both placenta and skin (i.e. the amniotic antibodies against BP 180(27). These antibodies are not epithelium of the placenta and umbilical cordon, and found in PUPPP, thus NC16A ELISA may be useful in basement membrane zone of the skin)(22,23). A smaller the differential diagnosis. NC16A ELISA has a high amount of antibodies are directed against BP 230. The sensitivity and specificity(8,11,12). Furthermore, ELISA immune process is based on an abnormal expression of is faster and less costly than immunoblotting(28-30). major histocompatibility complex class II molecules in the placenta, which act as a trigger for the inflamma- Differential diagnosis tory pathway(23). Recent studies have emphasized a The differential diagnosis of pruritic cutaneous lesi- possible role of T helper 2 lymphocytes subset, in the ons in pregnant women should include PUPPP, atopic production of the antibodies(24). eruption of pregnancy and intrahepatic cholestasis of Circulating antibodies, found in the serum of the pregnancy. PUPPP is the most common specific derma- patients, belong to immunoglobulin G class (subclass tosis of pregnancy. PUPPP mainly affect primiparous G1)(7). These antibodies bind to the extracellular women in the last trimester of pregnancy or immedia- NC 16A domain of the carboxyl terminus of the tely postpartum(31,32). The diagnosis is based on clinical 180 kDA bullous pemphigoid antigen. It seems that findings. Urticarial papules and plaques are seen on NC 16A contains epitopes that represent the main the limbs and abdomen(21). As in PG, lesions begin on target of the circulating autoantibodies. Then the the abdomen but the umbilical region is not involved. classical complement pathway activates, attracting Direct immunofluorescence is negative in PUPPP(5). eosinophils and lymphocytes. An inflammatory in- filtrate develops in the basement membrane zone Treatment and cellular mediators are released resulting in the PG is a rare disease, thus there are not many studies dermal-epidermal junction damage and blisters for- about the most appropriate therapeutic options. In mild mation(8,11,12).
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