RARE DISEASE
Epidermolysis bullosa acquisita
Epidermolysis bullosa acquisita
Epidermolysis bullosa acquisita
Synonyms: Acquired epidermolysis bullosa
Synonyms: Acquired epidermolysis bullosa
Synonyms: Acquired epidermolysis bullosa
Drug discovery
1
drug
With orphan designation
Overview
Epidermolysis bullosa acquisita (EBA) is a rare, chronic autoimmune subepidermal blistering disorder caused by IgG autoantibodies targeting type VII collagen, a critical component of dermal-epidermal anchoring fibrils. It manifests as trauma-induced blisters, mucosal involvement, and healing with scarring/milia. Diagnosis requires skin biopsy with direct immunofluorescence and salt-split indirect immunofluorescence. Treatment combines immunosuppression with meticulous wound care, but disease control remains challenging due to frequent resistance to therapy [1][2][7][12].
Population
Incidence: 0.08–0.5 cases/million/year, with higher rates in Germany (2.8/million) [2][12]
Onset: Bimodal peaks in early adulthood (20–30s) and later decades (50–70s); 5% pediatric cases [6][7][12]
Associations: Systemic lupus erythematosus, inflammatory bowel disease, and lichen planus (HR 3.1–26.9) [4][7][14]
Burden
Morbidity: Chronic scarring, nail dystrophy, ocular/corrosive mucosal lesions (50–65% of cases), and sepsis risk (HR 1.94) [4][7][12][14]
Cancer risk: 2.5× higher mortality vs. general population; squamous cell carcinoma in chronic lesions [4][9][12]
Quality of life: Severe pain, pruritus, and financial strain from wound care costs (~$20k/month in severe cases) [5][10][20]
Therapies
First-line: Systemic corticosteroids (0.5–2 mg/kg/day) ± dapsone or colchicine [1][2][7]
Refractory disease: Rituximab, IV immunoglobulin (IVIG), immunoadsorption, or cyclosporine; combination therapies show superior remission rates [3][8][14][18]
Supportive care: Infection prevention, non-adherent dressings, and nutritional support for mucosal lesions [6][10][12]
Categories: rare skin diseases
Research Papers
371 drug discovery papers about Epidermolysis bullosa acquisita, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
371 drug discovery papers about Epidermolysis bullosa acquisita, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-24 | Targeting neutrophil signaling networks in immune complex-mediated autoimmune disease
Abstract Fragment crystallizable gamma receptor (FcγR)-induced signaling is a crucial process that determines the cellular response to immune complexes (IC) in autoimmune diseases. In several diseases including pemphigoid diseases (PD), such as epidermolysis bullosa acquisita (EBA), or rheumatoid arthritis (RA), neutrophils are prominently involved as effector cells, while others such as immune thrombocytopenia (ITP) are independent of neutrophils. At the same time, most diseases are commonly treated by broad-range immunosuppression accompanied by severe risk for adverse effects. Signal transduction inhibitors (STIs) have been successfully applied in cancer therapy. However, their use in autoimmune diseases is an emerging, but so far understudied potential treatment avenue. Therefore, we screened a target-selective compound library consisting of 155 STIs in a neutrophil-based assay and conducted a multiplex kinase activity profiling with IC-stimulated neutrophils. Thus, we found novel potential therapeutic targets that were validated both in vitro in functional neutrophil assays and in vivo in murine models of EBA Here, we demonstrate that both systemic and topical treatment with several individual STIs is effective in a prophylactic approach in these models. Furthermore, therapeutic treatment with the BTK inhibitor ibrutinib in the immunization-induced EBA model reduced disease severity by approximately 85 % and showed efficacy in additional experimental models of EBA, arthritis, and ITP. Together, the present study contributes to the elucidation of FcγR-dependent signaling in neutrophils and identifies multiple novel promising treatment options including inhibition of PLC, PDK-1, PKC, p38, DNA-PK, KSP, c-Met, TBK-1 and BTK for IC-mediated autoimmune diseases.
2026-06-01 | Stenosing Esophageal Involvement in Acquired Epidermolysis Bullosa
Introduction Acquired epidermolysis bullosa (AEB) is a rare autoimmune subepidermal blistering disorder mediated by autoantibodies against type VII collagen. Mucosal lesions are frequent, but esophageal involvement remains exceptional. When present, it may cause progressive dysphagia linked to cicatricial strictures, with major nutritional impact and impaired quality of life. Case Report A 50-year-old man presented with bullous and post-bullous lesions on friction areas, associated with atrophic scarring and milia. Oral and nasal mucosal erosions were noted, with an 8-kg weight loss. Histopathology showed a subepidermal blister; direct immunofluorescence revealed linear IgG/C3 at the dermo-epidermal junction. ELISA demonstrated markedly elevated anti–type VII collagen antibodies and marginal anti-envoplakin positivity.Corticosteroids (0.5 mg/kg/day) were ineffective. Dapsone (100 mg/day) produced partial cutaneous improvement only. Endoscopy revealed a 7-cm circumferential mid-esophageal ulceration. Cyclosporine (3 mg/kg/day) induced transient improvement followed by progressive dysphagia.Repeat endoscopy showed an ulcerated cervical stricture with extensive mucosal detachment. Balloon dilation combined with high-dose corticosteroids and IVIG restored swallowing, improved weight, and prevented recurrence despite persistent mucosal fragility. Rituximab was subsequently initiated [ 1 ] [ 2 ] [ 3 ]. Discussion Esophageal involvement in AEB, although rare, represents a severe mucosal manifestation. Blistering, ulceration, and fibrotic strictures may occur, and endoscopy—while essential—is technically hazardous due to high mucosal fragility. Conventional therapies frequently fail to control severe mucosal disease. Endoscopic dilation is often required but carries procedural risks.Recent literature supports IVIG and rituximab as effective options in severe, refractory AEB, including stenosing esophageal forms, with favorable tolerance profiles. Conclusion Esophageal AEB necessitates individualized, multidisciplinary management. Biologic therapies offer promising perspectives for refractory and stenosing mucosal disease. Publication History Article published online: 05 June 2026 © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2026-05-08 | HLA genotype, clinical and immunofluorescence findings of 30 patients with type VII collagen antibody positive subepidermal bullous disease.
Epidermolysis bullosa acquisita (EBA) and mucous membrane pemphigoid are mucocutaneous blistering disorders that are associated with antibodies that target type VII collagen (anti-col7). There are relatively few studies that closely investigate the clinical phenotype and HLA genotype of patients who are anti-col7 positive. We therefore characterized all patients with anti-col7-positive subepidermal bullous disease that were treated at our centre. In total, 30 patients were identified, 29 had mechanobullous skin lesions and all had oral ulceration. The most common sites for oral lesions were the tongue, lip and palatal mucosa. Laryngeal and oesophageal lesions were seen in five and six patients, respectively. Oesophageal involvement was associated with erosions and stricture formation in the cervical or thoracic oesophagus and the majority of patients with oesophageal involvement had concomitant bullous pemphigoid180/230 antibodies and were of Black African ancestry. IgA deposition on direct immunofluorescence was associated with lower age at disease onset but did not correlate with clinical features or autoantibody profiles. Concomitant BP180/230 antibody positivity was associated with earlier disease onset and Black African ancestry. HLA genotyping was performed in 18 patients and demonstrated HLA-DQB1*03 and HLA-DQB1*06 alleles were most commonly associated with anti-col7 EBA. HLA genotype did not, however, correlate with clinical features of autoantibody profiles. Taken together, this study demonstrates that concomitant BP180/230 and anti-col7 antibodies are associated with earlier disease onset, Black African ancestry and potentially oesophageal involvement.
2026-03-30 | Tyrosine kinase signaling pathways as therapeutic targets in autoimmune subepidermal blistering skin diseases (pemphigoid diseases).
Pemphigoid diseases, such as bullous pemphigoid and epidermolysis bullosa acquisita, are severe organ-specific autoimmune diseases characterized by subepidermal skin blistering with increasing incidence in recent years. Although there have been substantial advances in understanding the pathomechanism of these diseases in the last decades, and the first specific therapy targeting the IL-4 and IL-13 pathway (dupilumab) has been approved by the FDA for bullous pemphigoid, further research is needed to eventually improve patient care. The characteristics of pemphigoid diseases include the formation of immune complexes and their recognition by Fcγ-receptors, as well as the development of a characteristic inflammatory cytokine microenvironment in the skin of the affected patients. Several non-receptor tyrosine kinases are involved in these events, playing a very important role in various signaling processes of immune cells. While certain Src-family kinases and the Syk tyrosine kinase play a very important role in signaling by Fcγ-receptors, JAK-family kinases are crucial players in the signaling of various cytokine receptors including, among others, the receptors of IL-4 and IL-13. The inhibition of these tyrosine kinases with small molecule inhibitors is an emerging therapeutic option in the treatment of an increasing number of immune-mediated diseases. Moreover, numerous studies have been conducted to examine proteins (including PLCγ2 and CARD9) in signal transduction following Fcγ-receptor activation in in vitro and in vivo experimental pemphigoid models, and an increasing number of case studies involving JAK inhibitors report the successful application of these drugs in various pemphigoid diseases. This review summarizes our current understanding of the therapeutically most promising tyrosine kinase signaling pathways in the pathogenesis of pemphigoid diseases.
2026-03-14 | Mechanical Skin Stress-Induced Lesion Development via ATP-Amplified Neutrophil Extracellular Trap Formation
ABSTRACT Neutrophilic skin diseases, including Behçet disease, Sweet syndrome, pyoderma gangrenosum (PG), and epidermolysis bullosa acquisita (EBA), are characterized by an exaggerated inflammatory response following mechanical skin stimulation, yet the underlying mechanisms remain unclear. We identify adenosine triphosphate (ATP) released from keratinocytes as a key mediator of this phenomenon, promoting neutrophil extracellular trap (NET) formation. Using an EBA murine model as a model of neutrophilic skin disease, where scratching (a prototypic mechanical stimulation) exacerbates lesional severity, we observed abundant NET deposition in lesional skin. Degradation of these NETs with DNase1 reduced clinical and histopathological severities. In vitro, purified NET components increased IL-8 secretion from keratinocytes and fibroblasts, suggesting that NETs amplify inflammation via a self-amplifying loop of neutrophil recruitment. In the EBA mouse, scratch restriction with neck collars not only attenuated clinical and histological disease severities but also decreased lesional NETosis and neutrophils. Mechanistically, keratinocytes released ATP in response to mechanical stress in vitro, and pharmacologic purinergic blockade in the EBA mice with suramin phenocopied the protective effects of scratch restriction. While ATP alone did not induce NETosis, ATP enhanced complement component 5a (C5a)-induced NET formation in vitro. These findings indicate that keratinocyte-derived ATP, released in response to mechanical stress, contributes to NETosis in a C5a-dependent manner, thereby exaggerating neutrophilic inflammation, leading to blistering and further NETosis. Histopathological analyses of EBA and PG cases also demonstrated NETs accumulation localized to the upper dermis, suggesting a conserved ATP-NET axis. Targeting this pathway may represent a promising therapeutic strategy for neutrophilic skin diseases.
2026-07-24 | Targeting neutrophil signaling networks in immune complex-mediated autoimmune disease
Abstract Fragment crystallizable gamma receptor (FcγR)-induced signaling is a crucial process that determines the cellular response to immune complexes (IC) in autoimmune diseases. In several diseases including pemphigoid diseases (PD), such as epidermolysis bullosa acquisita (EBA), or rheumatoid arthritis (RA), neutrophils are prominently involved as effector cells, while others such as immune thrombocytopenia (ITP) are independent of neutrophils. At the same time, most diseases are commonly treated by broad-range immunosuppression accompanied by severe risk for adverse effects. Signal transduction inhibitors (STIs) have been successfully applied in cancer therapy. However, their use in autoimmune diseases is an emerging, but so far understudied potential treatment avenue. Therefore, we screened a target-selective compound library consisting of 155 STIs in a neutrophil-based assay and conducted a multiplex kinase activity profiling with IC-stimulated neutrophils. Thus, we found novel potential therapeutic targets that were validated both in vitro in functional neutrophil assays and in vivo in murine models of EBA Here, we demonstrate that both systemic and topical treatment with several individual STIs is effective in a prophylactic approach in these models. Furthermore, therapeutic treatment with the BTK inhibitor ibrutinib in the immunization-induced EBA model reduced disease severity by approximately 85 % and showed efficacy in additional experimental models of EBA, arthritis, and ITP. Together, the present study contributes to the elucidation of FcγR-dependent signaling in neutrophils and identifies multiple novel promising treatment options including inhibition of PLC, PDK-1, PKC, p38, DNA-PK, KSP, c-Met, TBK-1 and BTK for IC-mediated autoimmune diseases.
2026-06-01 | Stenosing Esophageal Involvement in Acquired Epidermolysis Bullosa
Introduction Acquired epidermolysis bullosa (AEB) is a rare autoimmune subepidermal blistering disorder mediated by autoantibodies against type VII collagen. Mucosal lesions are frequent, but esophageal involvement remains exceptional. When present, it may cause progressive dysphagia linked to cicatricial strictures, with major nutritional impact and impaired quality of life. Case Report A 50-year-old man presented with bullous and post-bullous lesions on friction areas, associated with atrophic scarring and milia. Oral and nasal mucosal erosions were noted, with an 8-kg weight loss. Histopathology showed a subepidermal blister; direct immunofluorescence revealed linear IgG/C3 at the dermo-epidermal junction. ELISA demonstrated markedly elevated anti–type VII collagen antibodies and marginal anti-envoplakin positivity.Corticosteroids (0.5 mg/kg/day) were ineffective. Dapsone (100 mg/day) produced partial cutaneous improvement only. Endoscopy revealed a 7-cm circumferential mid-esophageal ulceration. Cyclosporine (3 mg/kg/day) induced transient improvement followed by progressive dysphagia.Repeat endoscopy showed an ulcerated cervical stricture with extensive mucosal detachment. Balloon dilation combined with high-dose corticosteroids and IVIG restored swallowing, improved weight, and prevented recurrence despite persistent mucosal fragility. Rituximab was subsequently initiated [ 1 ] [ 2 ] [ 3 ]. Discussion Esophageal involvement in AEB, although rare, represents a severe mucosal manifestation. Blistering, ulceration, and fibrotic strictures may occur, and endoscopy—while essential—is technically hazardous due to high mucosal fragility. Conventional therapies frequently fail to control severe mucosal disease. Endoscopic dilation is often required but carries procedural risks.Recent literature supports IVIG and rituximab as effective options in severe, refractory AEB, including stenosing esophageal forms, with favorable tolerance profiles. Conclusion Esophageal AEB necessitates individualized, multidisciplinary management. Biologic therapies offer promising perspectives for refractory and stenosing mucosal disease. Publication History Article published online: 05 June 2026 © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2026-05-08 | HLA genotype, clinical and immunofluorescence findings of 30 patients with type VII collagen antibody positive subepidermal bullous disease.
Epidermolysis bullosa acquisita (EBA) and mucous membrane pemphigoid are mucocutaneous blistering disorders that are associated with antibodies that target type VII collagen (anti-col7). There are relatively few studies that closely investigate the clinical phenotype and HLA genotype of patients who are anti-col7 positive. We therefore characterized all patients with anti-col7-positive subepidermal bullous disease that were treated at our centre. In total, 30 patients were identified, 29 had mechanobullous skin lesions and all had oral ulceration. The most common sites for oral lesions were the tongue, lip and palatal mucosa. Laryngeal and oesophageal lesions were seen in five and six patients, respectively. Oesophageal involvement was associated with erosions and stricture formation in the cervical or thoracic oesophagus and the majority of patients with oesophageal involvement had concomitant bullous pemphigoid180/230 antibodies and were of Black African ancestry. IgA deposition on direct immunofluorescence was associated with lower age at disease onset but did not correlate with clinical features or autoantibody profiles. Concomitant BP180/230 antibody positivity was associated with earlier disease onset and Black African ancestry. HLA genotyping was performed in 18 patients and demonstrated HLA-DQB1*03 and HLA-DQB1*06 alleles were most commonly associated with anti-col7 EBA. HLA genotype did not, however, correlate with clinical features of autoantibody profiles. Taken together, this study demonstrates that concomitant BP180/230 and anti-col7 antibodies are associated with earlier disease onset, Black African ancestry and potentially oesophageal involvement.
2026-03-30 | Tyrosine kinase signaling pathways as therapeutic targets in autoimmune subepidermal blistering skin diseases (pemphigoid diseases).
Pemphigoid diseases, such as bullous pemphigoid and epidermolysis bullosa acquisita, are severe organ-specific autoimmune diseases characterized by subepidermal skin blistering with increasing incidence in recent years. Although there have been substantial advances in understanding the pathomechanism of these diseases in the last decades, and the first specific therapy targeting the IL-4 and IL-13 pathway (dupilumab) has been approved by the FDA for bullous pemphigoid, further research is needed to eventually improve patient care. The characteristics of pemphigoid diseases include the formation of immune complexes and their recognition by Fcγ-receptors, as well as the development of a characteristic inflammatory cytokine microenvironment in the skin of the affected patients. Several non-receptor tyrosine kinases are involved in these events, playing a very important role in various signaling processes of immune cells. While certain Src-family kinases and the Syk tyrosine kinase play a very important role in signaling by Fcγ-receptors, JAK-family kinases are crucial players in the signaling of various cytokine receptors including, among others, the receptors of IL-4 and IL-13. The inhibition of these tyrosine kinases with small molecule inhibitors is an emerging therapeutic option in the treatment of an increasing number of immune-mediated diseases. Moreover, numerous studies have been conducted to examine proteins (including PLCγ2 and CARD9) in signal transduction following Fcγ-receptor activation in in vitro and in vivo experimental pemphigoid models, and an increasing number of case studies involving JAK inhibitors report the successful application of these drugs in various pemphigoid diseases. This review summarizes our current understanding of the therapeutically most promising tyrosine kinase signaling pathways in the pathogenesis of pemphigoid diseases.
2026-03-14 | Mechanical Skin Stress-Induced Lesion Development via ATP-Amplified Neutrophil Extracellular Trap Formation
ABSTRACT Neutrophilic skin diseases, including Behçet disease, Sweet syndrome, pyoderma gangrenosum (PG), and epidermolysis bullosa acquisita (EBA), are characterized by an exaggerated inflammatory response following mechanical skin stimulation, yet the underlying mechanisms remain unclear. We identify adenosine triphosphate (ATP) released from keratinocytes as a key mediator of this phenomenon, promoting neutrophil extracellular trap (NET) formation. Using an EBA murine model as a model of neutrophilic skin disease, where scratching (a prototypic mechanical stimulation) exacerbates lesional severity, we observed abundant NET deposition in lesional skin. Degradation of these NETs with DNase1 reduced clinical and histopathological severities. In vitro, purified NET components increased IL-8 secretion from keratinocytes and fibroblasts, suggesting that NETs amplify inflammation via a self-amplifying loop of neutrophil recruitment. In the EBA mouse, scratch restriction with neck collars not only attenuated clinical and histological disease severities but also decreased lesional NETosis and neutrophils. Mechanistically, keratinocytes released ATP in response to mechanical stress in vitro, and pharmacologic purinergic blockade in the EBA mice with suramin phenocopied the protective effects of scratch restriction. While ATP alone did not induce NETosis, ATP enhanced complement component 5a (C5a)-induced NET formation in vitro. These findings indicate that keratinocyte-derived ATP, released in response to mechanical stress, contributes to NETosis in a C5a-dependent manner, thereby exaggerating neutrophilic inflammation, leading to blistering and further NETosis. Histopathological analyses of EBA and PG cases also demonstrated NETs accumulation localized to the upper dermis, suggesting a conserved ATP-NET axis. Targeting this pathway may represent a promising therapeutic strategy for neutrophilic skin diseases.
Access all drug discovery papers and probability of success in trials forecasts:
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Drug Discovery Landscape
1 orphan drug designation for Epidermolysis bullosa acquisita.
1 orphan drug designation for Epidermolysis bullosa acquisita.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
(S)-2-(1-((6-amino-5-cyanopyrimidin-4-yl)amino)ethyl)-4-oxo-3-phenyl3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile | small molecules | FDA | 2017-01-05 | — | Almirall, S.A. |
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