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

2021 ◽  
Vol 12 ◽  
Author(s):  
Lifang Wen ◽  
Xiaoru Dong ◽  
Qing Li ◽  
Gabriele Schramm ◽  
Bing Zhang ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Local Anesthetic ◽  
Clinical Disease ◽  
Epidermolysis Bullosa Acquisita ◽  
Potential Contribution ◽  
Longitudinal Assessment ◽  
Disease Manifestation ◽  
Initiation Phase ◽  
Type Vii Collagen ◽  
Observation Period

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.

scholarly journals Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita

2021 ◽  
Vol 8 ◽  
Author(s):  
Hannah Zillikens ◽  
Anika Kasprick ◽  
Colin Osterloh ◽  
Natalie Gross ◽  
Michael Radziewitz ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Neutrophil Activation ◽  
Epidermolysis Bullosa Acquisita ◽  
Human Neutrophils ◽  
Selective Inhibitors ◽  
Effective Treatment Option ◽  
Disease Manifestation ◽  
Type Vii Collagen ◽  
The Impact

Class I phosphoinositide 3-kinases (PI3K) have been implemented in pathogenesis of experimental epidermolysis bullosa acquisita (EBA), an autoimmune skin disease caused by type VII collagen (COL7) autoantibodies. Mechanistically, inhibition of specific PI3K isoforms, namely PI3Kβ or PI3Kδ, impaired immune complex (IC)-induced neutrophil activation, a key prerequisite for EBA pathogenesis. Data unrelated to EBA showed that neutrophil activation is also modulated by PI3Kα and γ, but their impact on the EBA has, so far, remained elusive. To address this and to identify potential therapeutic targets, we evaluated the impact of a panel of PI3K isoform-selective inhibitors (PI3Ki) on neutrophil function in vitro, and in pre-clinical EBA mouse models. We document that distinctive, and EBA pathogenesis-related activation-induced neutrophil in vitro functions depend on distinctive PI3K isoforms. When mice were treated with the different PI3Ki, selective blockade of PI3Kα (alpelisib), PI3Kγ (AS-604850), or PI3Kβ (TGX-221) impaired clinical disease manifestation. When applied topically, only TGX-221 impaired induction of experimental EBA. Ultimately, multiplex kinase activity profiling in the presence of disease-modifying PI3Ki identified unique signatures of different PI3K isoform-selective inhibitors on the kinome of IC-activated human neutrophils. Collectively, we here identify topical PI3Kβ inhibition as a potential therapeutic target for the treatment of EBA.

Serial Measurement of Anti-type VII Collagen Antibodyis Useful in Treatment of Epidermolysis Bullosa Acquisita

2013 ◽  
Vol 75 (5) ◽  
pp. 409-414 ◽  
Author(s):  
Haruna SAWAKI ◽  
Amiko HAKUTA ◽  
Miwa KANAOKA ◽  
Kazuko NAKAMURA ◽  
Takashi HASHIMOTO ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Epidermolysis Bullosa Acquisita ◽  
Serial Measurement ◽  
Type Vii Collagen

scholarly journals Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

2013 ◽  
Vol 2013 ◽  
pp. 1-25 ◽  
Author(s):  
Ralf J. Ludwig
Keyword(s):  
Epidermolysis Bullosa ◽  
Clinical Presentation ◽  
Tissue Injury ◽  
Critical Role ◽  
Current Treatment ◽  
Epidermolysis Bullosa Acquisita ◽  
Target Antigen ◽  
In Vivo Models ◽  
Type Vii Collagen ◽  
Novel Therapeutic

Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. The pathogenic relevance of autoantibodies targeting type VII collagen (COL7) has been well-documented. Therefore, EBA is a prototypical autoimmune disease with a well-characterized pathogenic relevance of autoantibody binding to the target antigen. EBA is a rare disease with an incidence of 0.2 new cases per million and per year. The current treatment of EBA relies on general immunosuppressive therapy, which does not lead to remission in all cases. Therefore, there is a high, so far unmet medical need for the development of novel therapeutic options. During the last 10 years, several novel in vitro and in vivo models of EBA have been established. These models demonstrated a critical role of the genetic background, T cells, and cytokines for mediating the loss of tolerance towards COL7. Neutrophils, complement activation, Fc gamma receptor engagement, cytokines, several molecules involved in cell signaling, release of reactive oxygen species, and matrix metalloproteinases are crucial for autoantibody-induced tissue injury in EBA. Based on this growing understanding of the diseases’ pathogenesis, several potential novel therapeutic targets have emerged. In this review, the clinical presentation, pathogenesis, diagnosis, and current treatment options for EBA are discussed in detail.

scholarly journals Epidermolysis Bullosa Acquisita in Children: Case Series

2019 ◽  
Vol 18 (1) ◽  
pp. 56-64
Author(s):  
Nikolay N. Murashkin ◽  
Leonid A. Opryatin ◽  
Alexander I. Materikin ◽  
Eduard T. Ambarchyan ◽  
Roman V. Epishev ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Case Series ◽  
Basal Membrane ◽  
Final Diagnosis ◽  
Epidermolysis Bullosa Acquisita ◽  
Type Vii Collagen ◽  
Bullous Dermatosis ◽  
Medical Drug ◽  
Line Drug

Background. Epidermolysis bullosa acquisita (EBA) is chronic disease accompanied with subepidermal blistering on skin and mucous membranes as a result of autoimmune aggression to type VII collagen. EBA diagnostics in children is complicated due to similarity of clinical presentation with other bullous dermatosis in children.Clinical Case Description. The description of three clinical cases of EBA in children is provided. It is shown that for establishing the diagnosis it is necessary to estimate clinical evidence and to define the depth of blisters according to the results of histological examination of skin biopsy sample. Determination of IgG deposition positions relatively to the skin basal membrane due to performed indirect immunofluorescence test helps us to establish final diagnosis and specify patient management. Medical drug Dapsone was used in children with EBA, it has shown to be effective and safe to use as the first-line drug in management of such patients.Conclusion. The algorithm for EBA differential diagnosis with other bullous dermatosis in children is provided. Successful results of medical treatment are described. 

scholarly journals Bullous Systemic Lupus Erythematosus

2018 ◽  
Vol 19 (2) ◽  
pp. 123-125
Author(s):  
Sk Jakaria Been Sayeed ◽  
Md Mujibur Rahman ◽  
AKM Humayon Kabir ◽  
Md Moniruzzaman ◽  
Uzzal Mallik ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Bullous Pemphigoid ◽  
Epidermolysis Bullosa ◽  
Lupus Erythematosus ◽  
Dermatitis Herpetiformis ◽  
Epidermolysis Bullosa Acquisita ◽  
Systemic Lupus ◽  
Type Vii Collagen ◽  
Linear Iga Disease ◽  
Distinct Disease

Bullous systemic lupus erythematosus (BSLE) is extremely rare but distinct disease, characterized by vesicobullous skin eruptions in systemic lupus erythematosus (SLE). It can develop either before or after a diagnosis of SLE has been established. BSLE is characterized by a dermatitis herpetiformis-like histology and an autoimmunity to type VII collagen. It must be differentiated from other autoimmune vesicobullous diseases such as epidermolysis bullosa acquisita, dermatitis herpetiformis, linear IgA disease, and bullous pemphigoid. Its important to combine clinical, histological, and immunofluorescence findings to establish a diagnosis of BSLE. We report a case of BSLE to illustrate and emphasize the need for an integrative diagnostic approach.J MEDICINE JUL 2018; 19 (2) : 123-125

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