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.

Retrospective analysis of autoimmune bullous diseases in Middle Franconia.

Introduction: Autoimmune bullous diseases (AIBDs) are a group of rare cutaneous disorders affecting cornified skin and mucous membranes. They are characterized by tense or flaccid blistering and erosions due to autoantibodies against desmosomal and hemidesmosomal structural proteins of the skin. This group of disorders can be divided into those of pemphigoid and those of pemphigus diseases. If left untreated, these autoimmune diseases can cause serious or even life-threatening complications such as loss of fluid, superinfections or impaired food intake. Due to modern standardized serological assays, the diagnosis of AIBDs can usually be confirmed in combination with their clinical appearance. Whereas for a long time corticosteroids were the major players in the treatment of these diseases, with the approval of rituximab and other immunosuppressive agents, the therapy has increasingly improved. Methods: In this study, we aimed to investigate epidemiologic and clinical features as well as diagnostics and therapy of bullous autoimmune diseases in Middle Franconia, a governorate within the German federal state of Bavaria. Patients diagnosed or treated because of a AIBDs between 01.04.2013 and 31.03.2019 at the dermatological department of the university hospital Erlangen were included in this retrospective study (n = 242). Patients were either diagnosed for the first time (n=176) or the diagnosis has been confirmed (n=66) at the department. The respective incidence was calculated among the 176 subjects who had been diagnosed at the center in this period. Data was taken from patient records and analyzed with Microsoft® Excel. The evaluation included the diagnoses of pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), linear IgA dermatosis (LAD), epidermolysis bullosa acquisita (EBA), and dermatitis herpetiformis (DH). Results: This study shows that the incidence of each AIBDs in Middle Franconia is low and comparable (PV, PF, LAD, EBA) or lower (BP, MMP, DH) than in other studies and regions. BP is the most common newly diagnosed AIBD in Middle Franconia. Discussion: Due to the chronic and sometimes severe course of AIBDs, repeated in-house treatments are often necessary. To date, mainly topically and systemically applied corticosteroids in combination with immunomodulators are used as first-line therapy.

Luteolin peracetate and gossypolone inhibit immune complex-mediated neutrophil activation in vitro and dermal-epidermal separation in an ex vivo model of epidermolysis bullosa acquisita.

Introduction: Natural products have been shown to an important source of therapeutics for human disease. In this study, we aimed to identify natural compounds as potential therapeutics for epidermolysis bullosa acquisita (EBA), an autoimmune disease caused by autoantibodies to type VII collagen (COL7). Methods: Utilizing an in vitro experimental system, we screened a natural product library composed of 800 pure compounds for their inhibitory effect on COL7-anti-COL7 IgG immune complex (IC)-mediated neutrophil activation and on neutrophil-mediated tissue damage. Results: Three natural compounds, namely luteolin peracetate, gossypol, and gossypolone were capable in inhibiting the IC-induced neutrophil adhesion and oxygen burst in vitro. Furthermore, luteolin peracetate and gossypolone were able to inhibit the anti-COL7 IgG induced dermal-epidermal separation in an ex vivo model for EBA. Discussion: In summary, this study demonstrates that luteolin peracetate and gossypolone are potential therapeutics for experimental EBA, which deserves further investigation.

Case Report: Biological treatment of epidermolysis bullosa acquisita: report on four cases and literature review.

Epidermolysis bullosa acquisita (EBA) is a chronic, recurrent autoimmune subepidermal bullous disease characterized by the presence of autoantibodies targeting type VII collagen -- basement membrane zone antigen. Standard therapy for EBA includes a combination of systemic corticosteroids and dapsone; however, severe cases may require advanced treatment. The current article reports on four EBA cases in which biologics: infliximab, rituximab (Rtx), and intravenous immunoglobulin (IVIG) were applied. All patients fulfilled the clinical and immunological criteria of EBA: they presented tense blisters healing with atrophic scars on the skin on traumatized areas and in mucous membranes. The diagnosis of EBA was established using numerous techniques: direct and indirect immunofluorescence, salt split skin, ELISA, Fluorescence Overlay Antigen Mapping using Laser Scanning Confocal Microscopy. Since all the patients did not achieve long-term remission on standard treatment (prednisone, dapsone) due to ineffectiveness or side effects of drugs, they eventually were treated with biologics leading to extraordinary skin improvement and stopping the disease for 1-3 years. Biologics in all patients were tolerated very well. No side effects were observed during application as well as multi-month follow-up. The presented cases provide a premise that biological drugs can be a valuable component of EBA therapy.

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.

Acquired epidermolysis bullosa in a pediatric patient.

BACKGROUND: Acquired epidermolysis bullosa is a rare and chronic autoimmune subepidermal bullous disease characterized by the formation of autoantibodies against type VII collagen. Presentation in childhood is rare and with several manifestations. CASE REPORT: We report the case of a 12-year-old female patient who presented bullous and polymorphic lesions on the chest and extremities of several months of evolution. Due to the characteristics of the skin lesions, a histopathological and direct immunofluorescence study was conducted, confirming the diagnosis of acquired epidermolysis bullosa. Subsequently, corticosteroid and dapsone treatment was administered, with favorable clinical response during follow-up. CONCLUSIONS: Acquired epidermolysis bullosa is unusual in pediatric age, so it should be considered in the differential diagnosis of other congenital and acquired bullous diseases of childhood. The definitive diagnosis is performed through an immunofluorescence, study, which allows for rapid and effective treatment to control the disease and avoid permanent sequelae.

INTRODUCCIÓN: La epidermólisis bullosa adquirida es una enfermedad ampollar subepidérmica autoinmune, rara y crónica caracterizada por la formación de autoanticuerpos contra colágeno tipo VII. La presentación en la infancia es poco frecuente y con manifestaciones variables. CASO CLÍNICO: Se describe el caso de una paciente de sexo femenino de 12 años de edad que presentó lesiones ampollares y polimórficas en tórax y extremidades de varios meses de evolución. Por las características de las lesiones cutáneas, se realizó un estudio histopatológico y de inmunofluorescencia directa que confirmó el diagnóstico de epidermólisis bullosa adquirida, por lo que se administró tratamiento con corticoide y dapsona, con una respuesta clínica favorable durante el seguimiento. CONCLUSIONES: La epidermólisis bullosa adquirida es inusual en la edad pediátrica. Por tanto, debe considerarse en el diagnóstico diferencial de otras enfermedades ampollares congénitas y adquiridas de la infancia. El diagnóstico definitivo se realiza a través del estudio de inmunofluorescencia, lo que permite instaurar rápidamente un tratamiento rápido y eficaz para controlar la enfermedad y evitar secuelas permanentes.

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.

Treatment of Recurrent Epidermolysis Bullosa Acquisita With Tofacitinib.

This case report describes a patient with recurrent epidermolysis bullosa acquisita who was treated with tofacitinib.

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.

Epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome anchoring fibrils. The antigen-antibody binding elicits a complex inflammatory response, which culminates in the loss of dermo-epidermal adhesion of the skin and/or mucous membranes. Skin fragility with bullae, erosions, and milia in areas of trauma characterizes the mechanobullous form of the disease. In the inflammatory form of epidermolysis bullosa acquisita, urticarial inflammatory plaques with tense bullae, similar to bullous pemphigoid, or mucosal lesions can determine permanent scars and loss of functionality in the ocular, oral, esophageal, and urogenital regions. Due to the similarity of the clinical findings of epidermolysis bullosa acquisita with other diseases of the pemphigoid group and with porphyria cutanea tarda, the diagnosis is currently confirmed mainly based on the clinical correlation with histopathological findings (pauci-inflammatory subepidermal cleavage or with a neutrophilic infiltrate) and the demonstration of the presence of anti-collagen VII IgG in situ by direct immunofluorescence, or circulating anti-collagen VII IgG through indirect immunofluorescence and/or ELISA. There is no specific therapy for epidermolysis bullosa acquisita and the response to treatment is variable, usually with complete remission in children and a worse prognosis in adults with mucosal involvement. Systemic corticosteroids and immunomodulators (colchicine and dapsone) are alternatives for the treatment of mild forms of the disease, while severe forms require the use of corticosteroid therapy associated with immunosuppressants, intravenous immunoglobulin, and rituximab.

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.

Nutrition and bullous diseases.

Although relatively uncommon, autoimmune bullous diseases carry the risk of increased mortality and can significantly impact quality of life. This group of diseases is broad and encompasses subepidermal conditions such as bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis, and linear IgA bullous dermatosis, as well as intraepidermal conditions such as pemphigus and its variants. The pathophysiology of each condition is incompletely understood but broadly involves the formation of autoantibodies targeting skin adhesion proteins, a process that relies on a complex interplay between a dysregulated immune system, genetic predisposition, and environmental factors. We review the impact of nutrition on pathogenesis, clinical course, and treatment of various autoimmune bullous diseases.

The pathogeneses of pemphigus and pemphigoid diseases.

Autoimmune bullous diseases (AIBDs) are skin disorders which are mainly induced by autoantibodies against desmosomal or hemidesmosomal structural proteins. Previous studies using patients' samples and animal disease models identified target antigens and elucidated the mechanisms of blister formation. Pemphigus has been the subject of more active clinical and basic research than any other AIBD. These efforts have revealed the pathogenesis of pemphigus, which in turn has led to optimal diagnostic methods and novel therapies, such as rituximab. In bullous pemphigoid (BP), studies with passive-transfer mouse models using rabbit anti-mouse BP180 antibodies and studies with passive-transfer or active mouse models using autoantigen-humanized mice elucidated the immune reactions to BP180 in vivo. Recently, dipeptidyl peptidase-4 inhibitors have attracted attention as a trigger for BP. For epidermolysis bullosa acquisita (EBA), investigations using mouse models are actively under way and several molecules have been identified as targets for novel therapies. In this review, we give an overview and discussion of the recent progress in our understanding of the pathogenesis of pemphigus, BP, and EBA. Further studies on the breakdown of self-tolerance and on the identification of key molecules that are relevant to blister formation may expand our understanding of the etiology of AIBDs and lead to the development of novel therapeutic strategies.

Preventive but Not Therapeutic Topical Application of Local Anesthetics Can Inhibit Experimental Epidermolysis Bullosa Acquisita in Mice.

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disorder characterized and caused by autoantibodies against type VII collagen (COL7). Although it has been noticed that EBA in both patients and mice is associated with an increased scratching, it is not clear whether and how the scratching contributes to disease manifestation. Hence, we here aimed to validate this clinical observation and also to investigate the potential contribution of increased scratching in EBA pathogenesis in mice. Longitudinal assessment of scratching behavior revealed an increased frequency of scratching as early as 12 hours after injection of anti-COL7 IgG into the skin of mice. Subsequently, scratching events became even more frequent in mice. In contrast, mice injected with a control antibody showed an unaltered scratching behavior throughout the observation period. Based on these observations, we hypothesized that mechanical irritation may promote the induction of inflammation in experimental EBA. To challenge this assumption, the local anesthetic dyclonine hydrochloride was topically applied before injection of anti-COL7 IgG. Dyclonine hydrochloride reduced the scratching events and impaired clinical disease manifestation. In therapeutic experimental settings, i.e. administration of the local anesthetic 24 hours after injection of anti-COL7 IgG, dyclonine hydrochloride only inhibited the scratching behavior, but had no significant effect on clinical disease development. In addition, eosinophils were detected in the skin before the injection of anti-COL7 IgG and significantly increased 48 hours after the antibody injection. Collectively, our results suggest that scratching behavior contributes to the initiation phase of disease manifestation in experimental EBA.

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.