Clinical Features of Paediatric Inflammatory Epidermolysis Bullosa Acquisita: A Case Series Study.

Epidermolysis bullosa acquisita (EBA) rarely develops in childhood. This study retrospectively recruited paediatric patients with EBA (age ≤ 16 years), diagnosed by clinical and histopathological features and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA), and reviews their clinical manifestations, histopathology, immunological features, and responses to various treatments. All 7 included patients presented with inflammatory EBA. Among them, 3 had a bullous pemphigoid-like phenotype. Pathologically, in addition to dermal-epidermal blistering, in all patients, the distribution of neutrophils was superficial perivascular or interstitial, or in the dermal papilla. Mixed neutrophils and eosinophils were detected in 2 of the 3 patients with bullous pemphigoid-like phenotypes. In addition to treatment with glucocorticoids, dapsone was administered in 4 patients, while thalidomide and sulfasalazine were administered in 1 patient. All patients responded to the these therapies. Relapse was mainly due to reduction and cessation of glucocorticoids. In conclusion, EBA in childhood may be unique, and thus distinct from its adult counterpart. Specific treatment and follow-up protocols are required for therapy of this rare autoimmune skin disease in children.

A systematic review on efficacy, safety and treatment durability of intravenous immunoglobulin in autoimmune bullous dermatoses: Special focus on indication and combination therapy.

Autoimmune bullous diseases (AIBDs) are a group of rare blistering dermatoses of the mucous membrane and/or skin. The efficacy, safety and treatment durability of intravenous immunoglobulin (IVIg) as an alternative treatment should be explored to systematically review the available literature regarding treatment outcomes with IVIg in AIBD patients. The predefined search strategy was incorporated into the following database, MEDLINE/PubMed, Embase, Scopus and Web of Science on 18 July 2022. Sixty studies were enrolled using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The use of IVIg alone or combined with rituximab was reported in 500 patients with pemphigus, 82 patients with bullous pemphigoid, 146 patients with mucous membranes pemphigoid and 19 patients with epidermolysis bullosa acquisita. Disease remission with IVIg therapy and RTX + IVIg combination therapy were recorded as 82.8% and 86.7% in pemphigus, 88.0% and 100% in bullous pemphigoid and 91.3% and 75.0% in mucous membrane pemphigoid, respectively. In epidermolysis bullosa acquisita, treatment with IVIg led to 78.6% disease remission; no data were available regarding the treatment with RTX + IVIg in this group of patients. Among all the included patients, 37.5% experienced at least one IVIg-related side effect; the most common ones were headaches, fever/chills and nausea/vomiting. The use of IVIg with or without rituximab had a favourable clinical response in patients with AIBDs. IVIg has no major influence on the normal immune system, which makes its utilization for patients with AIBDs reasonable.

Epidermolysis Bullosa Acquisita in a patient with End Stage Renal Disease: Case study.

The clinical presentation of COVID-19 varies from being asymptomatic to developing acute respiratory distress syndrome and multi-organ dysfunction. The diffuse microvascular thrombi in multiple organs seen in the autopsy of COVID-19 patients are similar to that of thrombotic microangiopathy (TMA). TMA is characterised by thrombus formation in the microvasculature with laboratory findings of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. A 49-year-old male presented to the Aga Khan University Hospital, Karachi. with fever, diarrhoea, altered level of consciousness, and a positive nasopharyngeal swab for SARS-CoV-2. He developed severe thrombocytopenia, MAHA with 5.8% schistocytes, and worsening renal function on the sixth day of admission. Diagnosis of thrombotic thrombocytopenic purpura (TTP) was established based on PLASMIC score, and he was successfully treated with intravenous (IV) Methylprednisolone, therapeutic plasma exchange and IV Rituximab. The case emphasises the need to keep TTP in the differential diagnosis when a patient with COVID-19 develops severe thrombocytopenia, acute renal failure, or impaired level of consciousness, since prompt diagnosis and treatment is necessary to gain favourable outcome.

Intravenous Immunoglobulin for Autoimmune Bullous Diseases: A Case Series from a Central European Referral Center.

Background and Objectives: Autoimmune bullous diseases (AIBDs) may be treated with intravenous immunoglobulin (IVIG) infusions. This study aimed to evaluate the benefits and safety profiles of high-dose IVIG therapy in AIBD patients, as determined by clinical remission, the glucocorticosteroid-sparing effect, and adverse events at 12 months follow-up in a Central European university dermatology department setting. Materials and Methods: Our case series included 10 patients: five patients with pemphigus vulgaris, one with pemphigus herpetiformis, one with pemphigus foliaceus, one with bullous pemphigoid, two with epidermolysis bullosa acquisita. They underwent 4-12 monthly cycles of IVIG therapy at a dose of 2 g/kg per cycle. Results: The prednisone dosage reduction after 2, 6, and 12 months following the final IVIG course was 65.45%, 70.91%, and 76.37%, respectively. During the 12-month observation period, disease relapse was observed in 20% of patients, while others achieved complete or partial remission without or with minimal therapy. Side effects were seen in 80% of patients; they were transient and did not necessitate discontinuation of IVIG. Conclusions: IVIG demonstrates effectiveness as a treatment with a favorable safety profile. Nevertheless, its high cost remains a significant drawback, particularly in low-income countries. IVIG should be considered, especially in patients opposed to standard therapies or with contraindications to their use.

Use of Convolutional Neural Networks for the Detection of u-Serrated Patterns in Direct Immunofluorescence Images to Facilitate the Diagnosis of Epidermolysis Bullosa Acquisita.

The u-serrated immunodeposition pattern in direct immunofluorescence (DIF) microscopy is a recognizable feature and confirmative for the diagnosis of epidermolysis bullosa acquisita (EBA). Due to unfamiliarity with serrated patterns, serration pattern recognition is still of limited use in routine DIF microscopy. The objective of this study was to investigate the feasibility of using convolutional neural networks (CNNs) for the recognition of u-serrated patterns that can assist in the diagnosis of EBA. The nine most commonly used CNNs were trained and validated by using 220,800 manually delineated DIF image patches from 106 images of 46 different patients. The data set was split into 10 subsets: nine training subsets from 42 patients to train CNNs and the last subset from the remaining four patients for a validation data set of diagnostic accuracy. This process was repeated 10 times with a different subset used for validation. The best-performing CNN achieved a specificity of 89.3% and a corresponding sensitivity of 89.3% in the classification of u-serrated DIF image patches, an expert level of diagnostic accuracy. Experiments and results show the effectiveness of CNN approaches for u-serrated pattern recognition with a high accuracy. The proposed approach can assist clinicians and pathologists in recognition of u-serrated patterns in DIF images and facilitate the diagnosis of EBA.

Evidence for a role of extracellular heat shock protein 70 in epidermolysis bullosa acquisita.

Heat shock protein 90 (Hsp90) and Hsp70 are chaperones implicated in different inflammatory disorders, given their property to impact innate and adaptive immune responses. Here, we determined the so far unknown role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-mediated blistering dermatosis. The in vivo pathophysiological relevance of extracellular Hsp70 was demonstrated in an anti-type VII collagen antibody transfer-induced EBA mouse model in which elevated blood levels of this chaperone were recorded. We found that Hsp70-treated mice had a more intense clinical disease severity compared to controls that were paralleled by increased levels of cutaneous matrix metalloproteinase 9 and plasma hydrogen peroxide. The latter finding was confirmed in an independent reactive oxygen species release assay using EBA-specific immune complexes combined with recombinant Hsp70. Finally, cell culture experiments using human naive peripheral blood mononuclear cells (PBMC) revealed that extracellular Hsp70 stimulated the secretion of the T cell-derived pro-inflammatory cytokines IL-6 and IL-8. This work extends knowledge about the role of Hsps in autoimmune bullous diseases, suggesting that extracellular Hsp70 represents a pathophysiological factor and potential treatment target in EBA.

Epidermolysis bullosa acquisita: a case series of three paediatric patients.

Epidermolysis bullosa acquisita is a highly uncommon condition in the paediatric population. This article describes three children with this disease, different clinical presentation and management. It also reviews the most relevant articles on this topic.

Epidermolysis bullosa aquisita following immune-checkpoint inhibitor treatment for metastatic melanoma.

A case of epidermolysis bullosa aquisita following immunotherapy for melanoma. This adds to the repertoire of subepidermal blistering disorders documented following immune checkpoint therapy.

The association of six autoimmune bullous diseases with thyroid disorders: a population-based study.

BACKGROUND: The association of autoimmune bullous diseases (AIBDs) with thyroid disorders remains to be profoundly investigated. OBJECTIVE: To evaluate the epidemiological association between six AIBDs and thyroid disorders. METHODS: A population-based cross-sectional study enrolled patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with these six AIBDs were compared with six age- and sex-matched control groups regarding the prevalence of thyroiditis and hyperthyroidism. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for thyroid disorders. RESULTS: The study population included 1,743, 251, 106, 126, 860 and 103 patients with BP, MMP, EBA, PG, PV and PF respectively. The corresponding control groups consisted of 10,141, 1,386, 606, 933, 5,142 and 588 matched controls respectively. A significant association was found between thyroiditis and BP (OR, 1.98; 95% CI, 1.18-3.35; P = 0.010), MMP (OR, 7.02; 95% CI, 1.87-26.33; P = 0.004) and PV (OR, 2.73; 95% CI, 1.45-5.15; P = 0.002). With regards to hyperthyroidism, PF was the only AIBD to demonstrate significant comorbidity (OR, 2.42; 95% CI, 1.13-5.21; P = 0.024). EBA and PG were not found to cluster with any of the investigated thyroid conditions. CONCLUSION: Patients with BP, MMP, PV and PF experience an elevated burden of thyroid disorders. Patients with these AIBDs presenting with suggestive symptoms may be carefully screened for comorbid thyroid disorders.

Therapeutic approaches and targets for treatment of autoimmune bullous diseases.

Autoimmune bullous diseases are a heterogeneous group of diseases characterized by the development of cutaneous and mucosal vesicles, blisters, and finally erosions. The common pathogenetic mechanism is the presence of autoantibodies targeting structural proteins of the skin and mucous membranes (demosomes and hemidesmosomes): in the case of pemphigus, the antigens are intraepidermal, whereas in the case of pemphigoid, dermatitis herpetiformis, and epidermolysis bullosa acquisita they are subepidermal. Mucosal involvement typically affects the oral and ocular mucosa, but in some cases, the upper airways or the upper digestive tract are affected. The burden on patients' lives could be severe due to the impairment of normal feeding or breathing. In other cases, they may represent paraneoplastic syndromes. Since autoimmune bullous diseases may result in significant morbidity and mortality, depending on the grade of cutaneous and mucosal involvement, a prompt therapeutic approach is mandatory and, in recalcitrant cases, may be challenging. The first line therapy consists of corticosteroids, both topical and systemic. Once remission or control of the acute phase is obtained, adjuvant therapies need to be introduced in order to spare the corticosteroid load and minimize side effects such as iatrogenic diabetes or osteoporosis. Herein, we describe all current therapeutic approaches to autoimmune bullous diseases, also including emerging therapies.

Diagnosis of Epidermolysis Bullosa Acquisita: Multicentre Comparison of Different Assays for Serum Anti-type VII Collagen Reactivity.

Epidermolysis bullosa acquisita is a pemphigoid disease characterized by autoantibodies against type VII collagen. This study compared the sensitivity and specificity of 6 diagnostic assays: type VII collagen non-collagenous domains enzyme-linked immunoassay (NC1/2 ELISA) (MBL, Nagoya, Japan); type VII collagen NC1 ELISA (Euroimmun, Lübeck, Germany); indirect immunofluorescence (IF) microscopy test based on the expression of recombinant NC1 in a human cell line (NC1 BIOCHIP®; Euroimmun); full-length recombinant type VII collagen ELISA; immunoblotting with full-length type VII collagen in the extract of human dermis; and immunoblotting with recombinant NC1. Immunoblotting with recombinant NC1 showed a sensitivity of 93.1% and specificity of 100%, follow-ed by NC1 BIOCHIP® (sensitivity, 89.1%; specificity, 100%), immunoblotting with human dermis (sensitivity, 87.1%; specificity 100%), NC1-ELISA (sensitivity 82.2%; specificity 98.6%), NC1/NC2 ELISA (sensitivity 88.1%; specificity 93.3%), and full-length type VII collagen ELISA (sensitivity 80.2%; specificity 93.8%).

Diagnostic Value and Practicability of Serration Pattern Analysis by Direct Immunofluorescence Microscopy in Pemphigoid Diseases.

In pemphigoid diseases, direct immunofluorescence can be used to differentiate 2 patterns of antibody deposition at the dermal-epidermal junction; u- and n-serrated pattern. The u-serrated pattern is found in epidermolysis bullosa acquisita, and n-serrated pattern in all other pemphigoid diseases. To determine the detection frequency of these serrated patterns and the optimal thickness of biopsy cryosections, 2 patient cohorts obtained form our routine autoimmune laboratory were analysed; a retrospective cohort (n = 226) and a prospective cohort (n = 156). [AQ1] In 76% (291/382) of biopsies, a pattern was recog-nized, of which 96% (278/291) and 4% (13/291) had an n- or u-serrated pattern, respectively. A u-serrated pattern was seen in all epidermolysis bullosa acquisita biopsies confirmed by serology. No antibodies against type VII collagen were detected in any of the sera from biopsies with n-serrated pattern. No differences between the detection frequencies of serrated pattern were seen with respect to age, sex, biopsy site, or section thickness, while the detection frequency was higher in patients with serum anti-BP180 reactivity compared with those without. In conclusion, serrated pattern analysis using direct immunofluorescence has a high detection frequency and specificity for epidermolysis bullosa acquisita and will further facilitate the diagnosis of latter disorder.

The burden of neurological comorbidities in six autoimmune bullous diseases: a population-based study.

BACKGROUND: Apart from bullous pemphigoid (BP), the association of other autoimmune bullous diseases (AIBDs) with neurological conditions is poorly understood. OBJECTIVE: To estimate the association between a wide array of AIBDs and neurological conditions. METHODS: A retrospective cross-sectional study recruited patients with BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These patients were compared with their age- and sex-matched control subjects with regard to the lifetime prevalence of Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy and multiple sclerosis (MS). Logistic regression was used to calculate OR for specified neurological disorders. RESULTS: The current study included 1743, 251, 106, 126, 860 and 103 patients diagnosed with BP, MMP, EBA, PG, PV and PF, respectively. These patients were compared with 10 141, 1386, 606, 933, 5142 and 588 matched controls, respectively. Out of the investigated neurological conditions, PD associated with BP (OR, 2.71; 95% CI, 2.19-3.35); AD with BP (OR, 2.11; 95% CI, 1.73-2.57), MMP (OR, 2.37; 95% CI, 1.03-5.47), EBA (OR, 6.00; 95% CI, 1.90-18.97) and PV (OR, 2.24; 95% CI, 1.40-3.60); stroke with BP (OR, 1.84; 95% CI, 1.55-2.19) and EBA (OR, 2.79; 95% CI, 1.11-7.01); and epilepsy with BP (OR, 2.18; 95% CI, 1.72-2.77) and PV (OR, 1.80; 95% CI, 1.19-2.73). MS did not significantly cluster with any of the six AIBDs. CONCLUSION: In addition to BP, EBA and PV were found to cluster with neurological comorbidities. Patients with these AIBDs with compatible symptoms may be carefully assessed for comorbid neurological disorders.

Pediatric epidermolysis bullosa acquisita: A review.

Epidermolysis bullosa acquisita (EBA) is an acquired autoimmune blistering skin disorder that is rare in adults and even rarer in childhood. This review aims to identify cases of pediatric EBA and report their clinical features and course. Our literature review was conducted in MEDLINE® using the search terms related to juvenile epidermolysis bullosa acquisita. We identified 40 cases of pediatric EBA. Mucosal tissues were affected in 29 out of 40 cases. Treatment mostly consisted of a systemic corticosteroid combined with dapsone. Prognosis is favorable with 17 of 40 cases achieving complete remission, 9 of 40 with complete control with therapy, 12 of 40 with partial control with therapy, 1 of 40 with no response to therapy, and 1 of 40 terminating treatment early. Though it is a rare condition, childhood EBA should still be included in the differential diagnosis of pediatric blistering diseases.

A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation.

Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system.

12/15-Lipoxygenase choreographs the resolution of IgG-mediated skin inflammation.

Autoimmune diseases are defined by an immune response against a specific autoantigen, driven by antigen-specific T cells or antibodies. While the mechanisms resolving brief episodes of acute inflammation elicited by microbial components or tissue injury are well understood, the mechanisms resolving tissue inflammation in autoimmune diseases are still largely elusive. We have, therefore, addressed the mechanisms of resolution in IgG-mediated autoimmune diseases using a mouse model of the pemphigoid disease "bullous pemphigoid-like epidermolysis bullosa acquisita" (BP-like EBA) as prototypical example. We found that 12/15-LO is induced in skin lesions of BP-like EBA and is predominantly expressed in eosinophils. Dependent on the expression of 12/15-LO, large amounts of proresolving lipid mediators, are biosynthesized in the skin by the point disease peaks. Their production is timely correlated to the gradual reversal of tissue inflammation. Genetic deficiency in Alox15, the gene encoding 12/15-LO, disrupts this process significantly protracting and aggravating disease. This protraction is associated reduced recruitment of regulatory T cells (Tregs) into lesional skin. Intriguingly, Alox15-/- mice also exhibit reduced recruitment of eosinophils into the skin, and the chemotaxis of cultured Alox15-/- eosinophils towards CCL11/eotaxin-1 is compromised. Finally, we demonstrate that 15-lipoxygenase-1, the human homologue of 12/15-LO is induced in granulocytes in lesional skin of patients suffering from a pemphigoid disease. Collectively, our result uncover key mechanisms resolving IgG-mediated skin inflammation. These mechanisms are orchestrated by 12/15-LO expressed in eosinophils promoting the recruitment of eosinophils and Tregs, which in turn inhibit neutrophils.

Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form.

Mouse strains with specific deficiency of given hematopoietic lineages provide invaluable tools for understanding blood cell function in health and disease. Whereas neutrophils are dominant leukocytes in humans and mice, there are no widely useful genetic models of neutrophil deficiency in mice. In this study, we show that myeloid-specific deletion of the Mcl-1 antiapoptotic protein in Lyz2 Cre/Cre Mcl1 flox/flox (Mcl1 ΔMyelo) mice leads to dramatic reduction of circulating and tissue neutrophil counts without affecting circulating lymphocyte, monocyte, or eosinophil numbers. Surprisingly, Mcl1 ΔMyelo mice appeared normally, and their survival was mostly normal both under specific pathogen-free and conventional housing conditions. Mcl1 ΔMyelo mice were also able to breed in homozygous form, making them highly useful for in vivo experimental studies. The functional relevance of neutropenia was confirmed by the complete protection of Mcl1 ΔMyelo mice from arthritis development in the K/B×N serum-transfer model and from skin inflammation in an autoantibody-induced mouse model of epidermolysis bullosa acquisita. Mcl1 ΔMyelo mice were also highly susceptible to systemic Staphylococcus aureus or Candida albicans infection, due to defective clearance of the invading pathogens. Although neutrophil-specific deletion of Mcl-1 in MRP8-CreMcl1 flox/flox (Mcl1 ΔPMN) mice also led to severe neutropenia, those mice showed an overt wasting phenotype and strongly reduced survival and breeding, limiting their use as an experimental model of neutrophil deficiency. Taken together, our results with the Mcl1 ΔMyelo mice indicate that severe neutropenia does not abrogate the viability and fertility of mice, and they provide a useful genetic mouse model for the analysis of the role of neutrophils in health and disease.

Drug Development in Pemphigoid Diseases.

Pemphigoid diseases are organ-specific autoimmune diseases of the skin and/or mucous membranes. They are caused by autoantibodies targeting adhesion molecules located at the dermal-epidermal junction. While the diagnostics of pemphigoid diseases and insights into their pathogenesis have improved significantly, the development of novel treatments that are effective and safe remains an unmet medical need. However, numerous pre-clinical studies and early clinical trials have recently been launched. This review summarizes some pathways leading to drug development in pemphigoid diseases, namely: (i) hypothesis-driven drug development; (ii) omics-based drug development; (iii) drug repurposing; (iv) screening-based drug development; and (v) drug development based on careful clinical observations. Ultimately, it is hoped that this will lead to personalized and curative treatments.

Gastrointestinal involvement of primary skin diseases.

Less is known about gastrointestinal (GI) involvement of primary skin diseases due to the difference in embryology, histology, microbiology and physiology between integument and alimentary tract. Oesophagus, following the oropharyngeal mucosa, is the most common GI segment affected by primary skin diseases, especially by eosinophilic oesophagitis, lichen planus and autoimmune bullous dermatoses like pemphigus vulgaris, mucosal membrane pemphigoid and epidermolysis bullosa acquisita. Eosinophilic oesophagitis is an emerging chronic atopic disease with oesophageal dysfunction as the typical presentation, and oesophageal narrowing, rings and stricture as late complications. Oesophageal lichen planus mainly involves the proximal to mid-oesophagus in elderly aged women with long-term oral mucosal lesions. In acute attack of pemphigus vulgaris, oesophageal involvement is not uncommon but often neglected and may cause sloughing oesophagitis (oesophagitis dissecans superficialis) with acute GI bleeding in rare cases. GI manifestation of hereditary bradykininergic angio-oedema with colicky acute abdomen mostly affects small intestine, usually in the absence of pruritus or urticaria, and is more severe and long-lasting than the acquired histaminergic form. Strong evidence supports association between inflammatory bowel disease, especially Crohn disease, and hidradenitis suppurativa/acne inversa. Patients with vitiligo need surveillance of autoimmune liver disease, autoimmune atrophic gastritis or coeliac disease when corresponding symptoms become suspect. Melanoma is the most common primary tumour metastatic to the GI tract, with small intestine predominantly targeted. Gastrointestinal involvement is not uncommon in disseminated mycosis fungoides. Extramammary Paget's disease is an intraepidermal adenocarcinoma of controversial origin, and a high association between the anogenital occurrence and colorectal adenocarcinoma has been reported. As GI tract is the largest organ system with multidimensional functions, dermatologists in daily practice should be aware of the gastrointestinal morbidities related to primary skin diseases for an early diagnosis and treatment.

[Epidermolysis bullosa acquisita with Brunsting-Perry type pemphigoid: Diagnostic and therapeutic difficulties]. / Épidermolyse bulleuse acquise à type de pemphigoïde de Brunsting-Perry : difficultés diagnostiques et thérapeutiques.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare auto-immune blistering disease. We report a case of Brunsting-Perry pemphigoid diagnosed by immunoelectron microscopy (IEM). PATIENTS AND METHODS: A 46-year-old man presented very pruriginous vesicles on the face and neck present for 6 years and which were difficult to diagnose and treat. The appearance of atrophic scars and milium cycts evoked EBA, which was confirmed at IEM. Due to limited involvement of the face and the neck, we conclude on EBA of the Brunsting-Perry pemphigoid variant. Treatment with dapsone produced a favorable outcome. DISCUSSION: Diagnosis of EBA is often difficult. In a case review, Asfour et al. collated 60 cases of Brunsting-Perry pemphigoid. These patients had either anti-collagen VII or anti-BP180 and anti-BP230 antibodies. IEM showed cleavage either under the lamina densa or within the lamina lucida, suggesting that Brunsting-Perry pemphigoid is a subtype of EBA or bullous pemphigoid (BP), depending on the paraclinical elements, and localized to the head and neck. The majority of EBA-like cases required systemic therapy, whereas in the presence of BP antibodies, topical corticosteroids were effective. CONCLUSION: We report a case of EBA of the Brunsting-Perry pemphigoid type, diagnosed by IEM after 6 years of progression. We highlight the diagnostic and nosological difficulties of Brunsting-Perry pemphigoid. Classification of this dermatosis as a subtype of EBA or BP may enable effective adaptation of therapeutic management, which has not as yet been coded.