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.

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: Toward a better understanding of the etiopathogenesis.

Pemphigoid gestationis (PG) is the only autoimmune disease exclusively emerging in pregnancy. It belongs to the pemphigoid group of disorders, a class of autoimmune blistering skin diseases featuring an immune response against different hemidesmosomal proteins. PG is caused by a break of immunotolerance against the hemidesmosomal protein BP180. Several lines of evidence suggest that this break of immunotolerance is linked to specific maternal major histocompatibility complex (MHC) class II gene variants and aberrant expression of MHC class II molecules in the placenta. The close time association of the emergence of PG with pregnancy and the obviously very short period required from the initial break of immunotolerance to the onset of skin inflammation set PG into a unique position among autoimmune diseases in view of the fact that, for other autoimmune diseases, the time and site of the break of immunotolerance are usually vastly elusive and the period of silent disease can only be speculated on. In this review we highlight the features of PG and summarize current knowledge about its pathogenesis. We believe that this disease offers the best opportunity to elucidate comprehensively all phases of the pathogenesis of an autoantibody-driven disease.

Retrospective analysis of pemphigoid gestationis in 32 Saudi patients - Clinicopathological features and a literature review.

BACKGROUND AND OBJECTIVES: Pemphigoid gestationis (PG) is a rare autoimmune-mediated blistering disease that mainly affects pregnant women in their 2nd or 3rd trimester and immediate postpartum period. In addition to the clinical assessment, the diagnosis of PG is usually confirmed by histological and immunological studies. PG usually flares up at the time of delivery and spontaneously improves postpartum. Prompt recognition and appropriate management may reduce morbidity associated with this disorder. This study aimed to determine the clinical, histopathological features and treatment of PG of Saudi patients. MATERIALS AND METHODS: A retrospective study of 32 patients with pemphigoid gestationis (PG) was conducted from 1990 to 2014 at King Khalid University Hospital and Derma Medical Center, Riyadh, Saudi Arabia. Data regarding epidemiology, medical histories, clinical course, diagnostic test results and management were collected and analyzed. RESULTS: A total of 32 patients with PG were analyzed. The mean age was 31.9 years. Seventy-four percent of the patients were multigravidas, and 2 patients were primigravidas. One hundred percent of the cases were singleton pregnancies. Eighty-four percent of the cases had the onset of PG during the 2nd and 3rd trimesters. One hundred percent of patients complained of pruritus, and 94% reported this as the first symptom. Erythematous plaques and vesiculobullous eruption were the most common skin presentation. The primary sites of involvement were the abdomen, trunk, lower (mainly thighs) and upper limbs. The face and mucus membranes were rarely involved. Fifty percent of patients had recurrent symptoms with their next pregnancy. Direct immunofluorescence revealed a linear deposition of the third component of the complement along the basement membrane zone in all cases (C3),while most of the cases showed positive linear deposition of IgG. Seventy five percent of our patients had a good response to oral corticosteroids, and only one patient needed IVIG. The vast majority of the patients (61%) became free of symptoms within 1-2 months of treatment. In 53% of the patients, maternal and fetal outcomes were good with no complications. Six pregnancies were complicated by preterm labor, 2 experienced IUGR (intrauterine growth restriction), and 2 had an abortion or stillbirth. CONCLUSION: Our study does not differ dramatically when comparing the onset of PG, the high frequency of multigravida women, the clinical course and good patient outcomes but we observed that the first attack extended from primigravida to 11th pregnancy and slight increase in recurrence rate. Finally the timely diagnosis and appropriate management of PG may improve both maternal and neonatal outcome.

[Pemphigoid gestationis and Turner syndrome; an uncommon association]. / Pemphigoïde de la grossesse et syndrome de Turner ; une association inhabituelle.

The authors report an uncommon case of a pregnant woman with Turner syndrome (TS) whose pregnancy (with favorable outcome) was complicated by a pemphigoid gestationis in third trimester. This case points out that monitoring of these pregnancies is not limited to cardiac monitoring. Prevalence of auto-immune diseases is increased in the TS. Auto-immune dermatoses, such as pemphigoid gestationis, are one of the potential complications during pregnancy and should be known to practitioners.

Pemphigoid gestationis: a retrospective study in southwest Iran.

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis of pregnancy usually presents in the second or third trimester. It is characterized by pruritic, urticarial plaques with the development of tense vesicles and bullae within the lesions. Pathogenesis of PG is not fully established, however, most patients develop circulating autoantibodies targeting the bullous pemphigoid (BP) 180 antigen. The aim of this work is to draw a profile of the epidemiology, clinical aspects, treatment and evolution of the disease by studying hospital series. We retrospectively investigated the 13 patients who were diagnosed with PG based on hospital data at the Referral Center of Southwest Iran located in Ahvaz city between March 2002 and March 2011. The age of onset was 21 to 40 years (mean age: 27.5 years). The onset of the disease occurred in the second trimester of pregnancy in 6 patients and in the third trimester of pregnancy in 4 patients. One patient had a flare up of disease during the first trimester and two out of cases in puerperium period. In all cases, pruritus was the first symptom, followed by an erythematous vesiculobullous eruption.  The diagnosis of PG was confirmed by skin biopsy. Ten out of the patients treated with oral corticosteroids (0.5-1 mg/kg/day), one of the patients underwent oral corticosteroids plus topical glucocorticoid and the last patient treated with topical glucocorticoid. PG remains a rare dermatosis of pregnancy. Our series had two particularities compared to other studies: high frequency in primigravida and the frequent involvement of the face. Additionally our study demonstrated that improvement could occur faster and provide acceptable management if the treatment of the patients would be implemented sooner.

Pemphigus and pregnancy: a 23-year experience.

BACKGROUND: Studies on the interaction of pemphigus and pregnancy are limited to case reports and small case series. Pregnancy is not rare in Iranian pemphigus patients due to lower age at onset of the disease. AIM: We sought to investigate the outcome of pregnancy and the course of pemphigus in pemphigus patients in a retrospective study. METHODS: The files of 779 pemphigus women younger than 50 presenting to our center from 1984 till 2006 were examined for any mention of pregnancy. Data related to outcome of pregnancy and the course of the disease were collected. RESULTS: Sixty-six patients with a history of pregnancy were identified. Forty-eight known pemphigus patients experienced one or more pregnancies during their disease (total pregnancy number: 52). The course of pemphigus was as follows in this group: 28 cases (54%) of exacerbation, 15 cases (31%) with no alteration, and 9 cases (17%) showing improvement. The rate of abortion was 9.6% (5 cases). In 18 cases, the disease had started during pregnancy, 2 of them (11%) ended in an abortion. Overall, postpartum flare was seen in 33 cases (47.1%). CONCLUSION: Pemphigus may be exacerbated during or after pregnancy, but often to a mild degree. Although the rate of stillbirth was not as high as previously reported, the rate of abortion was considerable. Pregnancy may have an uneventful course, especially in patients in clinical remission; nevertheless, careful monitoring of the high risk mother and fetus is mandatory.

[Pemphigoid gestationis: a review]. / Pemphigoïde de la grossesse: revue de la littérature.

BACKGROUND: Pemphigoid gestationis (PG) is a rare auto-immune bullous disease occurring in one pregnant woman over 20,000 to 50,000. OBJECTIVE: Review of literature about physiopathology, immunological diagnosis and treatment of PG. METHODS: Research on Medline and Embase database without any time limit until April 2010. Because of the lack of randomized therapeutic trials in PG, retrospective series and case reports have been analyzed. RESULTS: PG is due to auto-antibodies directed against BP180 secondary to a mother-fetus immunological tolerance breaking. Blister formation results from a complex mechanism involving TH2 lymphocytes, cytokines and polymorphonuclear cells. Clinically, the disease is characterized by a pruritic, more or less extensive erythemato-papulous eruption. The presence of vesicles and/or blisters is inconstant but evocative. Recovery occurs generally in a few weeks after delivery but relapses are frequent in subsequent pregnancies. Combined oral contraception may also trigger flares of the disease. Diagnosis is confirmed by direct immunofluorescence showing linear C3±IgG deposits in the dermal-epidermal junction. ELISA BP180-NC16A method is very sensitive to detect circulating auto-antibodies. Fetal prognosis is good, but early onset in 1(st) or 2(nd) trimester and blister formation are risk factors for prematurity and low birth weight. Rarely the newborn may be affected by very transitory blisters. Efficiency of very potent topical corticosteroids has been showed in several studies, and they may be used as first-intent treatment in moderate forms of PG. Systemic corticosteroids are indicated in extensive forms. In very exceptional chronic or relapsing PG, immunosuppressant agents may be necessary. CONCLUSION: In the absence of consensus between moderate and severe forms of the disease, precise modalities of the steroid treatment (topical or systemic, duration and rhythm of decrease) are not well defined.

[Pemphigoid gestationis]. / Pemphigoïde gravidique.

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is characterized by a subepidermic separation induced by the presence of peripheral blood autoantibodies against two hemidesmosomal antigens: BPAG1 and BPAG2. Clinical diagnosis is confirmed by histology and positive cutaneous immunofluorescence tests. The most discriminant examination for other pruritic dermatoses of pregnancy is the enzyme-linked immunosorbent assay (Elisa) NC16A BP 180. First-line treatment is local corticosteroid therapy; if local treatment fails, general corticosteroid therapy should be administered. The prognosis is good for mother and child, except that there is a risk of preterm delivery and of moderate fetal growth restriction. Management in a specialized setting is therefore necessary. Recurrence is possible during subsequent pregnancies.

Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen).

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n=299) and from non-pregnant controls (n=134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p=0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function.

[Pemphgoid gestationis. A report of 30 cases]. / La pemphigoïde gravidique. A propos de 30 cas.

Pemphigoid gestationis is an acute autoimmune subepidermal bullous dermatosis which occurs during pregnancy and post partum. It is a rare disease which incidence vary from 1/1700 to 1/60000 pregnancy. It occurs in young woman aged between 20 to 40 years. The authors try throughout a retrospective study of 30 cases of pemphigoid gestationis to drave the epidemiological and clinical profile and the immunopathological characteristics of this affection.

[Incidence of herpes neonatorum in Netherlands]. / De incidentie van herpes neonatorum in Nederland.

OBJECTIVE: Investigation of the incidence of neonatal herpes in the Netherlands between 1992 and 1998. DESIGN: Inventory questionnaire survey. METHODS: All virological laboratories in the Netherlands were sent a questionnaire on the number of culture proven cases of neonatal herpes recorded between 1992 and 1998 and on the type of herpes simplex virus (HSV-1 or HSV-2). The gynaecological and paediatric departments of all university hospitals and of half of the general hospitals were sent questionnaires as well. Gynaecologists were asked how often caesarean section was performed in order to prevent neonatal herpes and how frequently pregnant women were seen with genital herpes. Paediatricians were asked how often they observed neonatal herpes, the type of HSV and the possible transmission route. Based on these data the figures for the whole of the Netherlands were estimated. RESULTS: The incidence of neonatal herpes in the Netherlands in the period 1992 to 1998 was 2.4 per 100,000 neonates. HSV-1 was the cause of neonatal herpes in 73%, HSV-2 in 9%, and in 18% of the cases the type of infection was not recorded. The number of pregnant women with genital herpes had increased, but, in agreement with a consensus statement, the gynaecologists hardly performed caesarean sections any more to prevent neonatal herpes (2 per year). CONCLUSIONS: The incidence of neonatal herpes in the Netherlands had not increased. There was no predominant role of HSV type 2 causing neonatal herpes.

Herpes gestacional / Herpes gestationis

Se presenta el caso clínico de una gestante con diagnóstico de herpes gestacional (herpes gestacional) con grandes ampollas en palmas y plantas de extremidades, además de las erupciones pruriginosas papulovesiculares clásicas en abdomen. Se hace una breve revisión de la literatura discutiéndose los aspectos etiopatogénicos y clínicos.

Specific pruritic diseases of pregnancy. A prospective study of 3192 pregnant women.

BACKGROUND AND DESIGN: For a period of 1 year, all pregnant women presenting with itching were investigated by clinical, histologic, immunopathologic, and laboratory studies. Fifty-one of 3192 pregnant women were studied. RESULTS: We identified (1) two typical cases of herpes gestationis, with an approximate incidence of one in 1700 pregnancies; (2) 22 cases of pruritus gravidarum, including five cases with a polymorphous skin eruption, with an incidence of one in 145 pregnancies; (3) 25 cases of polymorphic eruption of pregnancy, including diseases without maternal or fetal side effects and without criteria defining herpes gestationis or pruritus gravidarum, with an incidence of one in 130 pregnancies; and (4) two cases of intercurrent disease (one scabies and one exfoliative dermatitis). CONCLUSION: Our study is a prospective homogeneous account of pruritic dermatosis of pregnancy. Our results show that the incidence of herpes gestationis is higher than is usually reported in the literature and that pruritus gravidarum must be considered in the presence of itching occurring during pregnancy, with or without skin eruption.

Herpes gestationis.

Herpes gestationis is a rare autoimmune disease of pregnancy characterized by itching and skin lesions. The disease causes prominently maternal discomfort, but fetal and neonatal complications have been reported; however the frequency and severity of fetal illness are still debated. We describe three cases of herpes gestationis diagnosed and managed at our institution in the last 3 years.

Herpes gestationis.

Only 14 years have elapsed since immunofluorescence techniques revised our concept of herpes gestationis. As our inquiry broadens, the answers seem farther away. Yet much knowledge has been gained regarding predisposition and the pathomechanism of this elusive disease. I offer a review of historical context and an update on our current confusions regarding this rare autoimmune dermatosis of pregnancy.

Herpes gestationis in blacks.

To our knowledge, only two cases of herpes gestationis (HG) have been previously reported in black patients. We describe herein two black women with confirmed HG. Both had typical historical and clinical features of the disease. Direct immunofluorescence microscopy demonstrated complement deposition along the dermoepidermal junction in both women. Where HLA typing was possible (in one patient), the combination of HLA-DR3 and HLA-DR4 was found. In addition, anti-HLA-DR2 antibodies were present in serum samples taken from this patient. The occurrence of the HLA-DR3-DR4 combination has been reported to be greatly increased in whites with HG (43%, as compared with a 3% incidence in control subjects). The HLA-DR4 antigen is uncommon in American blacks, which may explain the infrequent occurrence of HG in this population. The occurrence of the DR2 antigen is increased in the husbands of women with HG, and this increase is most pronounced in the husbands of patients with the DR3-DR4 combination. The occurrence of positive immunofluorescence microscopy findings, together with the presence of a rare histocompatibility antigen combination previously associated with HG and the presence of anti-DR2 antibodies in the serum of one of our patients all suggest that HG is pathogenically identical in both blacks and whites.