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.

A Review Comparing International Guidelines for the Management of Bullous Pemphigoid, Pemphigoid Gestationis, Mucous Membrane Pemphigoid, and Epidermolysis Bullosa Acquisita.

Autoimmune blistering disease management can be challenging as treatment modalities vary greatly and no single standard of care exists. We consolidated the recommendations of international management guidelines in order to provide optimal management suggestions to physicians. A comprehensive literature search in PubMed/MEDLINE for published blistering disease management guidelines and consensus statements was conducted in November 2019. Search terms included "guideline or guidelines" or "consensus" and "pemphigoid" or "autoimmune blistering disease" or "epidermolysis bullosa acquisita". We included guidelines from established dermatologic societies and expert consensus groups. We excluded literature reviews, guidelines established by an association without dermatologists, or those specific to a single treatment. Guidelines in all languages were considered. Eleven guidelines from dermatologic associations and consensus groups meeting our inclusion criteria were selected. Several differences between recommendations, most notably when to introduce adjuvants for refractory disease, were found in bullous pemphigoid. In mucous membrane pemphigoid, treatment was directed to the sites involved and managed with systemic corticosteroids and immunosuppressants/biologics. There was no universal consensus on the first-line treatment for epidermolysis bullosa acquisita, but a combination of immunosuppressive, anti-inflammatory, and anti-neutrophil therapy was utilized. Comparison of the management guidelines revealed underrepresentation of guidelines from developing nations and key differences between the management styles among dermatologists from Europe and Asia. We attribute these discrepancies to the time elapsed between guidelines, regional differences, and demands of the local healthcare systems.

[Pemphigoid gestationis after egg donation : A case report]. / Pemphigoid gestationis bei Eizellspende : Ein Fallbericht.

Pemphigoid gestationis (PG) is a blistering autoimmune skin disease, typically occurring in the second and third trimester of pregnancy. Aberrant expression of major histocompatibility complex (MHC) class II molecules on the chorionic villi seems to lead to antibody production against bullous pemphigoid (BP)-180. We report a case of PG in a woman whose pregnancy was achieved using egg donation. Since the entire fetal genome is allogeneic to the mother, augmented immune reaction in egg-donated pregnancies appears to trigger the occurrence of PG.

Treatment Update of Autoimmune Blistering Diseases.

The treatment of refractory autoimmune blistering diseases (AIBDs) has always been a challenge. Because randomized controlled trials are lacking, treatment has been based on analysis of anecdotal data. The last 2 decades has seen the use of rituximab become a conventional treatment in the therapeutic armamentarium of AIBDs, leading to its Food and Drug Administration indication for pemphigus vulgaris in 2018. We review the current updated data on the use of rituximab including dosing, protocols, and its role in the algorithm of AIBDs. In addition, we discuss several promising novel emerging therapeutic agents for AIBDs.

Autoimmune bullous diseases during pregnancy: insight into pathogenetic mechanisms and clinical features.

Pemphigoid gestationis (PG), also known as herpes gestationis, is the prototypic pregnancy-associated autoimmune bullous disease (AIBD), but also the other AIBDs, notably pemphigus vulgaris, may begin or exacerbate during pregnancy. Although the increase in concentration of T and B regulatory cells makes pregnancy a state of increased immunologic tolerance toward the semiallogeneic fetal antigens, a prevalent T helper (Th) 2 profile, that is reported to be associated with pregnancy, may cause exacerbation of pemphigus and AIBDs in general during this period. Active disease may lead to stillbirth, spontaneous abortion, preterm pregnancy, low birthweight, and neonatal pemphigus. PG is a rare AIBD usually starting during the third trimester of pregnancy and healing in the postpartum. It is due to the formation of autoantibodies directed against different epitopes of bullous pemphigoid (BP) 180 as a consequence of the aberrant expression of BP180 in the placental tissue of genetically predisposed women. PG is characterized by vesicles with herpetiform distribution, blisters and urticarial elements typically involving the periumbilical area and the distal portion of the upper limbs. Diagnosis is based on: 1) physical examination; 2) histopathological pattern consisting of a dermal inflammatory infiltrate rich in eosinophils; 3) direct immunofluorescence test demonstrating linear deposits of complement fraction 3 and immunoglobulin G along the basement membrane zone; 4) detection of circulating autoantibodies by means of indirect immunofluorescence or enzyme linked immunosorbent assay. Here, we provide an updated overview on the pathophysiologic mechanisms of pregnancy-associated or pregnancy-exacerbated AIBDs, focusing also on peculiar clinical features of these disorders.

Pemphigoid gestationis successfully treated with intravenous immunoglobulin.

Pemphigoid gestationis (PG), also known as herpes gestationis, is a rare autoimmune blistering disease specific to pregnancy, which usually presents in the second or third trimesters and, in 15%-25% of cases, during the immediate postpartum period.1Although the ethiopathogeny of PG is not fully clarified, most patients develop antibodies against a 180 kDa transmembrane hemidesmosomal protein (BP180; BPAG2; collagen XVII).2 PG has a strong association with human leucocyte antigens DR3 and DR4.3We report a case of a 29-year-old female patient with PG successfully treated with intravenous immunoglobulin.

A subset of patients with pemphigoid (herpes) gestationis has serological evidence of celiac disease.

BACKGROUND: Pemphigoid (herpes) gestationis (PG) is an uncommon, self-limited disease with other autoimmune associations; however, celiac disease (CD) is not recognized as one. METHODS: From 71 patients' sera submitted for herpes gestationis factor (HGF) testing over a 5-year period, 12 were consistent with PG demonstrating HGF and increased IgG BP180 antibody levels; these sera were tested for IgA and IgG endomysial antibodies (EMA), epithelial basement membrane zone and cell surface antibodies by indirect immunofluorescence, and for IgA and IgG tissue transglutaminase (transglutaminase 2 or TG2) antibodies, IgA epidermal transglutaminase (transglutaminase 3 or TG3) antibodies, IgG BP230, and IgG desmoglein 1 and desmoglein 3 antibodies by enzyme-linked immunosorbent assays (ELISAs). RESULTS: Three of 12 patients' sera with PG (25%) had CD antibodies with positive IgA EMA and increased IgA TG2 antibody levels; two of these had positive IgG EMA, and one other had an increased IgA TG3 antibody level. CONCLUSIONS: A subset of patients with serological findings of PG also has serological evidence of CD, which may have implications in the etiopathogenesis of PG and which reveals important information about the mother's, and possibly her infant's, health.

Itch in Pregnancy Management.

Pruritus is common in pregnancy. It deserves an elaborated work-up of the patient. It is frequently a symptom of a dermatosis that coincides by chance with pregnancy or a preexisting dermatosis that can flare during pregnancy. In some cases, it is due to the group of pregnancy-specific dermatoses. Work-up requires a prudent consideration of the diagnostic tests as well as the choice of treatment because of the potential effects on the fetus. This chapter will focus on the specific dermatoses of pregnancy and the local and systemic treatment of pruritus in general during pregnancy.

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.

Bullous diseases: Kids are not just little people.

Bullous diseases may be rare; however, this does not preclude the clinician from being familiar with their manifestations and treatment. After ruling out infection, genetically inherited blistering diseases are more likely to be the cause of blistering or erosions in the neonatal period, whereas immunobullous diseases are more common in adults. Published literature on immunobullous disorders reflects information gleaned from case reports and open-label case series; prospective studies and evidence-based treatments are limited. Although there may be overlapping clinical features, significant clinical differences exist between adults and children. Evidence-based treatment guidelines are limited, and information from the adult literature cannot be readily generalized to the pediatric population. This paper reviews the approach to blistering conditions and the differences among bullous pemphigoid, linear immunoglobulin A disease, dermatitis herpetiformis, pemphigus foliaceus, pemphigus vulgaris, and paraneoplastic pemphigus in adult versus pediatric patients.

Skin disease in pregnancy.

Skin manifestations during pregnancy are common and diversified. This review will focus on the most important entities to be recognized by obstetricians. These are, on the one hand, physiological changes, where unnecessary investigations should be avoided, and on the other, the specific dermatoses of pregnancy. These develop electively in pregnancy, and they are currently grouped into three disorders: polymorphic eruption of pregnancy, atopic eczema of pregnancy, and pemphigoid gestationis. Arguments for recognition of these are presented including detection of anti-BP180 antibodies. Follow-up and treatment depend on the precise diagnosis. Risks in fetal prognosis may occur in rare pemphigoid gestationis cases.

Positive clinical outcome with IVIg as monotherapy in recurrent pemphigoid gestationis.

Pemphigoid gestationis (PG) is an autoimmune blistering disease associated with pregnancy. It is characterized by the presence of autoantibodies against bullous pemphigoid antigens in the basement membrane zone. A 32 year old female developed PG in the first pregnancy and had a stillbirth. PG recurred during the second trimester of her second pregnancy. Systemic corticosteroid therapy was cause for concern since patient developed gestational diabetes. Patient was unwilling to use insulin. Intravenous immunoglobulin (IVIg) was used as a treatment of last resort. The dose was 2g/kg/cycle. It was given every two weeks antepartum and every three weeks for three months postpartum. PG improved within four weeks of IVIg therapy. Serum and tissue immunopathological studies were negative prior to delivery. A healthy neonate was born. No adverse events to IVIg were observed. No disease was observed ten months postpartum.

Clinical and immunological profiles of 25 patients with pemphigoid gestationis.

BACKGROUND: Systematic study of pemphigoid gestationis (PG) has not been performed owing to its rarity. OBJECTIVES: To perform clinical and immunological analyses of 25 patients with PG. METHODS: In addition to clinical and histopathological assessments, we performed immunofluorescence (IF), immunoblotting (IB) and enzyme-linked immunosorbent assays (ELISAs). RESULTS: PG developed preferentially during the second or third trimester of pregnancy, with a mean age at onset of 30·5 years. Histopathology showed subepidermal blisters less frequently. Direct IF showed C3 deposition in the basement membrane zone (BMZ) in all patients, with rare reactivity with keratinocyte cell surfaces. Ninety-two per cent of patients showed circulating IgG anti-BMZ autoantibodies during indirect IF of either normal or 1 mol L(-1) NaCl-split skin. Complement IF revealed linear C3 reactivity with the BMZ of normal skin in 68% of patients, and all patients had C3 reactivity on the epidermal side of 1 mol L(-1) NaCl-split skin. IB and ELISA of the NC16a domain of BP180 recombinant protein was positive in 96% and 92% of patients, respectively, while only four patients had a positive ELISA for BP230. In IB tests, 28% of patients reacted with the C-terminal domain of BP180 and 20% reacted with leucocyte adhesion deficiency-1 protein. Multigravidae developed PG during a significantly (P < 0·01) earlier stage (21·1 weeks) of pregnancy than primigravidae (31·3 weeks). CONCLUSIONS: IB and ELISA of the NC16a domain of BP180 were shown to be sensitive and diagnostic methods in PG. Patients with PG rarely reacted with BP230, suggesting a different pathogenesis between PG and bullous pemphigoid. Multigravidae developed PG skin lesions significantly earlier in pregnancy than primigravidae.