Conjunctival involvement in the autoimmune blistering dermatoses: a clinical and histopathological study

The conjunctiva was examined by slit lamp microscopy and biopsy for direct immunofluorescence (IF) in patients with cicatricial pemphigoid (CP), bullous pemphigoid (BP), pemphigoid gestationes (PG), linear IgA dermatosis (LAD), pemphigus and dermatitis herpetiformis (DH).
In CP, five of 13 patients had definite scarring, seven equivocal, and one no signs. IF showed linear deposition of IgG and/or C₃ along the BMZ in 45%.
In BP, six of 18 patients had fine conjunctival scarring. IF showed linear IgG IgA and/or C₃ in 73 %. Scarring was not observed in one PG patient.
In LAD, three of seven patients had conjunctival scarring, one with marked symblepharon. IF in five patients showed linear IgG without IgA in three.
In pemphigus, neither of two patients had scarring. IF in both showed IgG and/or C3 between epithelial cells.
In DH, one of three patients had fine scarring.
These findings demonstrate that conjunctival involvement may occur in autoimmune bullous dermatoses other than CP and LAD.     

IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis

Please cite this paper as: IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis. Experimental Dermatology 2010; 19: 648–653. Background: Patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigoid gestationis (PG) have IgG antibodies against BP180 and BP230, components of the hemidesmosomes. Patients with linear IgA bullous dermatosis (LABD) have IgA autoantibodies against a 97/120‐kDa protein which is highly homologous to a shedded fragment of the BP180‐ectodomain. Objectives: The aim of our study was to determine the incidence of IgA autoantibodies directed against BP180/BP230 in the pemphigoids and LABD and to determine the antigenic regions that are targeted by IgA autoantibodies. Methods: Utilizing baculovirus‐expressed recombinant BP180 and BP230 proteins, we performed immunoblot analyses for IgA reactivity of sera from patients with BP (n = 30), MMP (n = 10), PG (n = 6), LABD (n = 6) and from control patients with non‐related pruritic dermatoses (n = 8). Results: IgA reactivity against BP180 and/or BP230 was detected in 19/30 of the BP, in 7/10 of the MMP, in 6/6 of the LABD and in 3/6 of the PG sera, respectively, but not in the control group. In all subgroups, the major antigenic site recognized by IgA antibodies was located within the NH₂‐terminus of the BP180‐ectodomain, but only a minority of the sera showed also IgA reactivity against the BP180‐NC16a‐domain. IgA reactivity against the central domain of BP180 was more frequently seen than against its COOH‐terminus. IgA against the COOH‐ and NH₂‐terminus of BP230, respectively, was detected in 6/30 of the BP, 1/10 of the MMP, 1/6 of the LABD and 0/8 control sera. Conclusion: IgA reactivity against BP180 and/or BP230 is a common finding in the pemphigoids.     

80例大疱性皮肤病组织病理及直接免疫荧光结果分析

目的：探讨组织病理及直接免疫荧光检查对大疱性皮肤病的诊断意义。方法：对80例大疱性皮肤病患者的皮损进行组织病理检查,并采用鼠抗人免疫球蛋白（IgG,IgM,IgA）及补体C3进行直接免疫荧光检查,对结果进行回顾性分析。结果：本组患者自身免疫性大疱性皮肤病占60.00%,以天疱疮和类天疱疮为主,非自身免疫性大疱性皮肤病以大疱性表皮松解症及大疱性多形红斑多见,不同类型的大疱性皮肤病组织病理及免疫荧光具有特征性。结论：组织病理及直接免疫荧光检查对大疱性皮肤病的诊断、鉴别诊断、治疗、预后判断具有重要的意义。     

A Cross-sectional Study of Direct Immunofluorescence in the Diagnosis of Immunobullous Dermatoses

Background:

Autoimmune blistering diseases are a group of bullous disorders characterized by pathogenic antibodies directed at the target antigens, which are components of the desmosomes or adhesion complex at the dermoepidermal junction. Direct immunofluorescence (DIF) is invaluable in the diagnosis of these lesions.

Aim:

The aim of this study was to evaluate the sensitivity of DIF in immunobullous dermatoses and to study the pattern of DIF. The study also aims to correlate DIF with clinical and histologic findings and to analyze discrepancies.

Materials and Methods:

Total 100 biopsies received over a period of 2 years in the Department of Pathology were analyzed. DIF, histopathology and clinical data were reviewed.

Results:

Out of 100, 89 cases showed DIF patterns concordant with clinical/histologic diagnosis. The sensitivity of DIF was 94.44% (51/58) in the pemphigus and 84% (21/25) in the bullous pemphigoid (BP) group, 100% each in dermatitis herpetiformis (2/2) and linear IgA disease (1/1). A total of 11 histologically proven cases of immunobullous lesions were DIF negative-four (three of pemphigus vulgaris and one of BP) due to having no epidermis, three (cases of BP) owing to sampling/technical errors and the remaining four (cases of pemphigus vulgaris) due to being on treatment.

Conclusion:

Immunofluorescence helps confirm the diagnosis of bullous lesions in which there is clinical and the histopathologic overlap. Sampling errors contributed to false negative (FN) results.     

Frequency of IgA antibodies in pemphigus, bullous pemphigoid and mucous membrane pemphigoid

Circulating and bound IgA antibodies can be found in the autoimmune blistering diseases, but their prevalence, clinical relevance and target antigens remain unknown. Thirty-two patients with pemphigus, 73 with bullous pemphigoid and 28 with mucous membrane pemphigoid were studied retrospectively. Direct immunofluorescence (DIF) analysis of IgG, IgA, IgM and C3 was carried out for all cases. Sera were studied by standard indirect immunofluorescence, indirect immunofluorescence on salt-split skin, immunoblotting for bullous pemphigoid and mucous membrane pemphigoid and ELISA for pemphigus. With DIF, we found IgA autoantibodies in 22 of all 133 cases. Circulating IgA antibodies to skin were detected in 2 of 3 IgA-DIF-positive patients with pemphigus, in 3 of 6 with bullous pemphigoid, and in 6 of 13 with mucous membrane pemphigoid. We confirm that the IgA reactivity is more frequently associated with mucous membrane involvement, especially in cases without critical involvement (5/8). The role of IgA and its antigenic specificity in these diseases remain unclear.     

2825例皮肤病患者皮损直接免疫荧光检查结果分析

目的为了探讨直接免疫荧光检查对某些皮肤病的意义。方法采用抗人Ｉｇ（ＩｇＧ、ＩｇＡ、ＩｇＭ和补体Ｃ３）直接免疫荧光技术对２８２５例（８９个病种）皮肤病患者皮损作了检查。结果９２６例系统性红斑狼疮皮损区基底膜阳性占９５％,曝光区正常皮肤基底膜阳性占８０％,而２８７例盘状红斑狼疮皮损基底膜阳性占９２％,曝光区正常皮肤均阴性;６２例混合结缔组织病皮损区阳性为８５％;１８４例皮肌炎皮损血管壁阳性７０％;７３例系统性硬皮病皮损区阳性７０％;２１１例寻常型银屑病皮损区角质层阳性９３％;１２５例寻常性天疱疮皮损区表皮细胞间阳性９５％;８５例大疱性类天疱疮的阳性为９２％;７１例疱疹样皮炎的阳性为９０％;１１６例血管炎病灶区血管壁阳性为９０％。结论提示ＳＬＥ、ＤＬＥ及大疱性皮肤病皮损的免疫荧光标记形态具有特征性改变。而且,直接免疫荧光检查对其它皮肤病的诊断与鉴别诊断也有重要意义。     

Annular bullous diseases

Annular bullous dermatoses represent an etiologically diverse group of cutaneous phenomena that present with a figurate morphology in association with vesicles and bullae. This group of diverse conditions consists of bullous pemphigoid; pemphigoid gestationis; epidermolysis bullosa simplex, Dowling-Meara type; linear immunoglobulin A bullous dermatosis; chronic bullous disease of childhood; anti-p200 pemphigoid; subcorneal pustular dermatosis; and immunoglobulin A pemphigus. Astute examination of clinical, histopathologic, and serologic features is crucial in distinguishing these bullous dermatoses. We review the clinical presentation, pathophysiology, histopathology, and treatments for each bullous annular disease to aid physicians in their recognition, diagnosis, and management.     

Non‐paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans

Bronchiolitis obliterans is a small‐airway obstructive lung disease for which immunologically mediated pathogenesis is supposed. Frequent association of bronchiolitis obliterans with paraneoplastic pemphigus is well known, but its association with other autoimmune bullous diseases has not been reported except for a case of anti‐laminin‐332‐type mucous membrane pemphigoid in a patient with chronic graft‐versus‐host disease. We report a case of non‐paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans in a patient without transplantation. Although the patient's serum contained immunoglobulin (Ig)A antibodies to the 180‐kDa bullous pemphigoid antigen/type XVII collagen and IgG antibodies to laminin‐332, diagnosis of either linear IgA bullous dermatosis or mucous membrane pemphigoid could not be made because of the failure to detect linear IgA deposition at the basement membrane zone by direct immunofluorescence and the lack of mucous membrane lesions. Physicians should be aware that autoimmune bullous diseases other than paraneoplastic pemphigus can also associate with this rare but potentially fatal lung disease.     

Spectrum of autoimmune bullous diseases in Iran: a 10-year review

Background Autoimmune bullous diseases (ABDs) are potentially devastating bullous dermatoses of the skin and mucosae characterized by the presence of tissue‐bound and circulating antibodies directed against disease‐specific target antigens. These diseases comprise two major subgroups of subepidermal autoimmune bullous disorders and pemphigus, based on the level of blister formation. Although they occur worldwide, the relative frequencies of different ABDs show wide geographical variation. Most epidemiological studies on ABDs have focused on single diseases or a group of diseases; published surveys studying the whole spectrum of diseases are scarce. Objectives This study aimed to assess the relative frequencies of different ABDs in patients presenting to the Bullous Diseases Research Center, Tehran, Iran. Methods Medical files for all newly diagnosed patients with ABD presenting to the Center between March 1997 and February 2006 were examined. Patients with dermatitis herpetiformis were not included. Results A total of 1402 patients were diagnosed with ABD during the study period. Pemphigus vulgaris (PV) was the most common ABD (81.2%), followed by bullous pemphigoid (BP) (11.6%), pemphigus foliaceus (PF) (4.4%), pemphigoid gestationis (0.7%), mucous membrane pemphigoid (0.7%), epidermolysis bullosa acquisita (0.5%), linear immunoglobulin A (IgA) disease (0.4%), paraneoplastic pemphigus (0.2%), IgA pemphigus (0.2%), and pemphigus erythematosus (0.1%). The mean age at diagnosis and male : female ratio were 43.4 years and 1 : 1.39, 42.2 years and 1 : 1.34, and 59.4 years and 1 : 1.36 for PV, BP, and PF, respectively. Conclusions Pemphigus vulgaris was the most frequent ABD according to our study; cases of PV outnumbered those of BP by a ratio of almost 8 : 1. This finding contrasts with those of studies conducted in Western European countries, in which BP predominates. There was a female predominance in most subtypes of ABD. Mean age at onset of PV and BP was lower than in Europe. In view of its large population of PV patients, Iran should be considered a suitable field for future clinical trials.     

Immunofluorescence testing in the diagnosis of autoimmune blistering diseases: overview of 10-year experience

BACKGROUND

Immunofluorescence testing is an important tool for diagnosing blistering diseases.

OBJECTIVE

To characterize the immunofluorescence findings in patients diagnosed with autoimmune blistering skin diseases.

METHODS

We retrospectively analyzed immunofluorescence results encompassing a 10-year period.

RESULTS

421 patients were included and divided into 2 groups: group 1- intraepidermal blistering diseases (n=277) and 2- subepidermal blistering diseases (n=144). For group 1, positive DIF findings demonstrated: predominance of IgG intercellular staining (ICS) and C3 for pemphigus foliaceus-PF (94% and 73% respectively), pemphigus vulgaris-PV (91.5%-79.5%) and paraneoplastic pemphigus-PNP (66%-33%); ICS IgA in 100% of IgA pemphigus cases, and IgG deposits in the basement membrane zone (BMZ) along with ICS in one Hailey-Hailey patient. The IIF findings revealed mean titers of 1:2.560 for PV and 1:1.280 for PF. For paraneoplastic pemphigus, IIF was positive in 2 out of 3 cases with rat bladder substrate. In group 2, positive DIF findings included multiple deposits at basement membrane zone for epidermolysis bullosa acquisita-EBA (C3-89%,IgG-79%,IgA-47%,IgM-21%) mucous membrane pemphigoid-MMP (C3,IgG,IgA,IgM-80%) and bullous pemphigoid-BP (C3-91%,IgG-39%,IgA-11%,IgM-6%), and IgA at basement membrane zone for IgA linear disease (99%) and dermatitis herpetiformis-DH (dermal papillae in 84.6%). For lichen planus pemphigoides, there was C3 (100%) and IgG (50%) deposition at basement membrane zone. indirect immunofluorescence positive findings revealed basement membrane zone IgG deposits in 46% of BP patients, 50% for EBA, 15% for IgA linear dermatosis and 50% for LPP. Indirect immunofluorescence positive results were higher for BP and EBA with Salt-Split skin substrate.

CONCLUSION

Our results confirmed the importance of immunofluorescence assays in diagnosing autoimmune blistering diseases, and higher sensitivity for indirect immunofluorescence when Salt-split skin technique is performed.     

Neonatal Autoimmune Blistering Disease: A Systematic Review

We aimed to better understand the pathogenesis, clinical features, prognosis, and treatment of neonatal autoimmune blistering diseases (AIBDs). We searched Medline, Embase, PubMed, Latin American and Caribbean Health Sciences Literature, and reference lists of identified articles. Inclusion criteria were articles published from 1946 to December 2014 in any language. Exclusion criteria were age greater than 4 weeks and no confirmed AIBD diagnosis. We identified 51 cases of neonatal AIBDs: 34 cases of pemphigus (31 pemphigus vulgaris [PV], 3 pemphigus foliaceus [PF]) and 17 cases of pemphigoid diseases (9 bullous pemphigoid [BP], 5 linear immunoglobulin A bullous dermatosis [LABD], 1 BP and LABD, 1 epidermolysis bullosa acquisita, 1 bullous systemic lupus erythematosus). Pemphigoid diseases had a higher male predominance (male:female ratio 4.6:1) than pemphigus (male:female ratio 1:1.06) (p = 0.004). Pemphigus had a higher proportion presenting at birth (79.4%) than pemphigoid diseases (29.4%) (p = 0.008). The most common sites involved were the trunk (63.0%), followed by the head and neck (60.9%). The mucosal membranes were involved in 32.6% of cases (27.6% in pemphigus, 41.6% in pemphigoid diseases). Only 33.3% used systemic therapy, and 75.5% achieved control within 3 weeks. Most PV, PF, and BP cases, but not LABDs, reported maternal disease. In pemphigus cases, 75.0% of mothers had active disease and 25.0% were in control. Pregnant women with PV, PF, and PG of any severity can passively transfer autoantibodies leading to neonatal AIBD. Pemphigoid diseases are more likely to present after birth and may be more male predominant. The presentation of LABDs may be different from that of all other AIBDs.     

UV light-induced linear IgA dermatosis

Various exogenous factors (eg, drugs, dietary antigens, trauma, infections, radiographs, and UV radiation) are known to induce or aggravate skin diseases. UV radiation in particular is known to induce or aggravate the autoimmune bullous diseases of pemphigus foliaceus, pemphigus vulgaris, and bullous pemphigoid. Its role in linear IgA dermatosis, however, is not well recognized. We report the second case of linear IgA dermatosis induced by intense sun exposure in which blistering was induced by UVA radiation. Furthermore, a review of the literature on photoinduced autoimmune bullous diseases and the wavelengths responsible for the induction of blistering is presented and several proposed mechanisms of action for the blister induction, including release or unmasking of antigens, promotion of antibody fixation by UV radiation, and launching of an inflammatory process, are discussed. We conclude that linear IgA dermatosis should be added to the list of autoimmune bullous diseases induced and/or aggravated by UV radiation.     

Refractory bullous pemphigoid leaving numerous milia during recovery

Recovery with milia may occur in bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA). Scarring commonly occurs in MMP and EBA. Here, we report a 62‐year‐old man patient with BP, who was left with numerous milia during recovery. The patient had immunoglobulin (Ig)G autoantibodies to the recombinant protein of the BP180‐NC16a domain and the soluble 120‐kDa ectodomain of BP180 (linear IgA bullous dermatosis [LAD]‐1). There are cases of BP with IgG autoantibodies to LAD‐1 and/or the recombinant protein of BP180 C‐terminal domain. Extensive milia formation during recovery may be associated with immunological predisposition and/or improper interaction between hemidesmosomes and the extracellular matrix components.     

The expanding spectrum of IgA pemphigus: a case report and review of the literature

IgA pemphigus (IGAP) is a rare, distinct variant of pemphigus, currently classified, depending upon the histological features, immunofluorescence staining pattern and autoantibody profile, into two types: subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis. In a patient with a widespread blistering disease of the skin resembling SPD‐type IGAP, we demonstrate the coexistence of IgA reactivity to both epidermal (desmocollins 2 and 3) and basement membrane‐associated (BP180) proteins, suggesting the coexistence of atypical IGAP and linear IgA bullous dermatosis, respectively. This case, together with 20 previous reports of atypical IGAP, underscores the limitations of current classification schemes. Therefore, we suggest reclassifying these cases under the general term ‘IGAP spectrum’.     

IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with bullous and cicatricial pemphigoid and linear IgA bullous dermatosis

BACKGROUND: Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180. OBJECTIVES: We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes. METHODS: Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180. RESULTS: All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180. CONCLUSIONS: The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures.     

Case of linear immunoglobulin A bullous dermatosis associated with acquired hemophilia

Linear immunoglobulin (Ig)A bullous dermatosis is a rare autoimmune subepidermal bullous dermatosis caused by circulating IgA autoantibodies directed against the antigens at the basement membrane zone. Most linear IgA bullous dermatosis cases are idiopathic, but some are associated with the use of certain drugs, infections, lymphoproliferative disorders, internal malignancies, autoimmune disorders, collagen diseases or, very rarely, other skin diseases, including autoimmune bullous diseases. Acquired hemophilia is also rare; it is a coagulation disease caused by anti-factor VIII IgG antibodies. Acquired hemophilia has been reported to be associated with malignant tumors, pregnancy or postpartum, drug reactions, collagen diseases such as rheumatoid arthritis, autoimmune disorders, and skin diseases such as psoriasis and pemphigus. We report a case of hemophilia acquired during the course of linear IgA bullous dermatosis and review reported cases of autoimmune bullous dermatoses associated with acquired hemophilia.     

Occult Herpes Simplex Virus Colonization of Bullous Dermatitides

Background: Acantholytic disorders, including pemphigus vulgaris, chronic benign familial pemphigus (Hailey-Hailey disease, superficial pemphigus), Darier disease, and Grover transient acantholytic dermatosis, as well as other vesiculo-bullous disorders, including bullous pemphigoid, epidermolysis bullosa, and atopic dermatitis, are prone to florid infections by herpes simplex virus (HSV)-I and -II, and, more rarely, by varicellazoster virus (VZV). As these infections are difficult to recognize clinically and histologically, their frequency remains unknown. A possible occult viral colonization has never been documented in these disorders. The manner in which the primary bullous disorders are contaminated by herpesviridae remains unclear. Objective: To retrospectively assess the possible presence of HSV and VZV in a series of biopsies of acantholytic disorders and bullous pemphigoid. Method: The typical α-herpesviridae-related cytopathic signs were searched for by conventional microscopy in skin biopsies of patients with bullous pemphigoid (n = 20), pemphigus vulgaris (n = 19), Darier disease (n = 18), chronic benign familial pemphigus (n = 3), and Grover transient acantholytic dermatosis (n = 3). Immunohistochemistry (IHC) targeted specific HSV-I, HSV-II, and VZV antigens. Polymerase chain reaction (PCR) was used for detecting HSV- and VZV-specific DNA sequences. Results: No cytopathic signs suggestive of HSV or VZV infection were detected. However, IHC revealed HSV antigens in Darier disease (1/18, HSV-I), Grover transient acantholytic dermatosis (1/3, HSV-I), pemphigus vulgaris (1/19, HSV-I), and bullous pemphigoid (2/20, HSV-I and HSV-II). In these IHC-positive cases, PCR amplified specific HSV primers in Darier disease (1/18), pemphigus vulgaris (1/19), and bullous pemphigoid (1/20). VZV antigens and nucleic acids were never identified. The HSV antigens were nearly always restricted to the upper part of the granular layer and thus differed from the usual HSV distribution during cutaneous infection. Negative and positive controls yielded consistently positive and negative results, respectively. Conclusion: This report shows for the first time that clinically and histologically occult HSV colonization may occur in Darier disease, Grover transient acantholytic disease, pemphigus vulgaris, and bullous pemphigoid. Given the frequent use of immunosuppressive treatments for primary bullous disorders, greater awareness of HSV colonization and infection is recommended in these patients.     

抗BP180NC16A IgG亚型检测方法的建立以及在大疱性类天疱疮中的意义

【摘要】 目的 建立抗BP180NC16A IgG亚型的检测方法,并探讨其在大疱性类天疱疮（BP）中的意义。方法 原核表达GST-NC16A融合蛋白,并采用亲和层析法纯化。优化ELISA关键环节,建立抗BP180NC16A IgG各亚型的ELISA检测方法,并对10例未经治疗的BP、5例妊娠疱疹、1例成人线状IgA大疱性皮病、2例天疱疮患者血清分别进行检测。结果 通过方阵测定法确定GST-NC16A融合蛋白的包被浓度为500 μg/L,包被条件为4 ℃ 12 h,血清稀释倍数为1 ∶ 100,酶标二抗为1 ∶ 2000,孵育条件为37 ℃ 1 h,底物反应条件37 ℃ 20 min。10例大疱性类天疱疮患者10例IgG1阳性,9例IgG2阳性,5例IgG3阳性,9例IgG4阳性。2例寻常型天疱疮、1例成人线状IgA大疱性皮病均阴性。5例妊娠疱疹所有亚型均阳性,以IgG1和IgG3亚型为主。结论 抗BP180NC16A ELISA检测法特异性强、重复性好,是检测BP和妊娠疱疹患者抗BP180NC16A抗体亚型的半定量方法。     

Review of autoimmune blistering diseases: the Pemphigoid diseases

Autoimmune Blistering Diseases of the Pemphigoid type is characterised by sub‐epidermal blisters (SEB) with circulating autoantibodies against components of the basement membrane zone (BMZ). The main disorders to date include bullous pemphigoid (BP), pemphigoid gestationis, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), linear IgA disease (LABD), dermatitis herpetiformis (DH), lichen planus pemphigoides and bullous lupus. This is in contrast to pemphigus and related disorders, which demonstrate intraepidermal acantholysis and a positive Nikolsky sign. The classification and management is based on clinical, histological and direct and indirect immunofluorescence findings. There are, however, overlapping clinical and histological features between the conditions and clinical heterogeneity within each disease.     

Polymorphic pemphigoid. Is it still worth using this terminology?

The term polymorphic pemphigoid has been used in the literature as a variant of bullous pemphigoid. But this term is imprecise and now obsolete, since patients with linear IgA dermatosis have been reported under this terminology. The patients who develop an atypical subepidermal bullous disease with clinical and histological features of both bullous pemphigoid and dermatitis herpetiformis may actually be classified into three groups: (1) vesicular variant of bullous pemphigoid; (2) linear IgA dermatosis, and (3) mixed subepidermal bullous disease.