Review
Medicine, General & Internal
Desa Tesanovic Perkovic, Zrinka Bukvic Mokos, Branka Marinovic
Summary: Epidermolysis bullosa acquisita (EBA) is a rare autoimmune disease that causes blistering of the skin and mucous membranes. It is caused by autoantibodies attacking type VII collagen, which leads to detachment of the epidermis and blister formation. EBA has two major clinical subtypes: mechanobullous and inflammatory variants. The mechanobullous variant presents with skin fragility, minimal inflammation, and scarring, while the inflammatory variant is challenging to differentiate from other autoimmune bullous diseases. Conventional treatment for EBA is difficult, but novel therapeutic strategies are being explored to improve patient quality of life.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Immunology
Stefan Tukaj, Jagoda Mantej, Krzysztof Sitko, Detlef Zillikens, Ralf J. Ludwig, Katja Bieber, Michael Kasperkiewicz
Summary: Stress-induced heat shock protein 70 (Hsp70) plays a crucial role in autoimmune processes, with highly immunogenic extracellular Hsp70 activating immune responses and contributing to the development of inflammatory/autoimmune disorders. Anti-Hsp70 autoantibodies are significantly increased in patients with epidermolysis bullosa acquisita (EBA), an autoimmune blistering skin disease, and are positively correlated with pro-inflammatory interferon gamma (IFN-γ) levels. These autoantibodies promote EBA development by enhancing neutrophil infiltration and activating the NF-κB signaling pathway in an IFN-γ-associated manner.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Franziska Schauer, Alexander Nystroem, Manfred Kunz, Stefanie Huebner, Sarah Scholl, Ioannis Athanasiou, Svenja Alter, Judith Fischer, Cristina Has, Dimitra Kiritsi
Summary: Collagen VII is a key component for attaching the epidermis to the dermal extracellular matrix. Dysfunction of collagen VII leads to two disorders, EBA and DEB, which share clinical similarities. Our study suggests that testing for COL7A1 genetic variants should be considered in EBA patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Dermatology
Elena Pipi, Anika Kasprick, Hiroaki Iwata, Stephanie Goletz, Jennifer E. Hundt, Hengameh Sadeghi, Leon F. Schmidt-Jimenez, Enno Schmidt, Jonathan Sjogren, Detlef Zillikens, Ralf J. Ludwig, Mattias Collin, Katja Bieber
Summary: This study investigates the impact and molecular mechanism of high-dose IgG treatment in murine autoantibody-induced skin inflammation. The findings suggest that high-dose IgG treatment can improve the clinical manifestations of autoimmune skin diseases by reducing the amount of antibodies, scavenging ROS, and inhibiting complement activation.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Letter
Dermatology
Birao Fan, Mingyue Wang
Summary: This case report discusses the use of tofacitinib in the treatment of a patient with recurrent epidermolysis bullosa acquisita.
Article
Dermatology
Denise Miyamoto, Juliana Olivieri Gordilho, Claudia Giuli Santi, Adriana Maria Porro
Summary: Epidermolysis bullosa acquisita is a rare autoimmune disease characterized by the loss of dermo-epidermal adhesion of the skin and/or mucous membranes due to the synthesis of anti-collagen VII autoantibodies. Diagnosis is mainly based on clinical correlation, histopathological findings, and immunological tests.
ANAIS BRASILEIROS DE DERMATOLOGIA
(2022)
Review
Immunology
Konrad Szymanski, Cezary Kowalewski, Ewelina Pietrzyk, Katarzyna Wozniak
Summary: Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune disease characterized by autoantibodies targeting type VII collagen. Standard therapy includes corticosteroids and dapsone, but biologics such as infliximab, rituximab, and IVIG have shown promise in severe cases. This article presents four EBA cases treated with biologics, resulting in significant improvement and disease cessation for 1-3 years, with no observed side effects during treatment or follow-up. These cases suggest that biologics may be a valuable addition to EBA therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dermatology
Mareike Becker, Nina Schumacher, Enno Schmidt, Detlef Zillikens, Christian D. Sadik
Summary: The study suggests that IgA EBA may be more common than expected and may require more intensive systemic treatment, indicating that it should be considered as a separate disease entity.
Article
Immunology
Khalaf Kridin, Artem Vorobyev, Cristian Papara, David A. De Luca, Katja Bieber, Ralf J. Ludwig
Summary: Identification of risk factors and sequelae of diseases is crucial for primary prevention and disease management. This study used TriNetX to identify risk factors and sequelae of the rare autoimmune disease EBA. The findings revealed chronic inflammatory diseases, especially lupus erythematosus and lichen planus, as the highest risk factors for EBA development and metabolic and cardiovascular diseases, and thrombosis as the most common sequelae after EBA diagnosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Daniel L. Seiler, Katja H. Kaehler, Marie Kleingarn, Christian D. Sadik, Katja Bieber, Joerg Koehl, Ralf J. Ludwig, Christian M. Karsten
Summary: This study demonstrates the important role of C5aR2 in regulating the activation and function of neutrophils in response to C5a, and its potential impact on the expression of Fc gamma receptors and CD11b. These findings highlight the significance of C5aR2 in the pathogenesis of neutrophil-mediated autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dermatology
Paul Schilf, Marie Schmitz, Aleksandra Derenda-Hell, Markus Thieme, Tabea Bremer, Martin Vaeth, Detlef Zillikens, Christian D. Sadik
Summary: The study showed that 2-deoxy-D-glucose and metformin attenuated the disease in the EBA model, highlighting glycolysis and oxidative phosphorylation in neutrophils as promising therapeutic targets for EBA. Additionally, the research indicated that intact mitochondria are necessary for neutrophil responses in the context of EBA.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Immunology
Lifang Wen, Xiaoru Dong, Qing Li, Gabriele Schramm, Bing Zhang, Detlef Zillikens, Ralf J. Ludwig, Frank Petersen, Xinhua Yu
Summary: The study suggests that scratching behavior may contribute to the initiation phase of disease manifestation in experimental EBA, and mechanical irritation may promote the induction of inflammation.
FRONTIERS IN IMMUNOLOGY
(2021)
Letter
Dermatology
Thilo Gambichler, E. Schmidt, Christina H. Scheel, Maria Chatzipantazi
Summary: A 32-year-old man with a history of Crohn's disease developed blisters and inflammatory lesions after 1 year of ustekinumab treatment, and was diagnosed with epidermolysis bullosa acquisita. He was treated with dapsone.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2023)
Article
Dermatology
Daniel Leonard Seiler, Marie Kleingarn, Katja Hendrika Kahler, Caroline Gruner, Jovan Schanzenbacher, Elvira Ehlers-Jeske, Samyr Kenno, Christian David Sadik, Enno Schmidt, Katja Bieber, Jorg Kohl, Ralf J. Ludwig, Christian Marcel Karsten
Summary: This study reveals the proinflammatory role of C5aR2 in the pathogenesis of antibody-induced tissue damage in epidermolysis bullosa acquisita (EBA).
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Dermatology
Stefan Tukaj, Jagoda Mantej, Krzysztof Sitko, Marta Bednarek, Detlef Zillikens, Ralf J. Ludwig, Katja Bieber, Michael Kasperkiewicz
Summary: The study revealed the previously unknown role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA) and suggested it as a potential treatment target. Experimental findings indicated that Hsp70 may exacerbate the clinical severity of EBA by promoting inflammatory responses and oxidative stress.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Dermatology
Khalaf Kridin, Ralf J. Ludwig
Summary: In this retrospective cohort study, patients with acne treated with isotretinoin had a lower risk of depression compared to those treated with oral antibiotics, but a comparable risk of major depressive disorder. The risk of suicidal attempts was similar between the two groups, but patients under isotretinoin had a higher risk of suicidal ideation. Patients under isotretinoin also had a lower risk of post-traumatic stress disorder, anxiety, bipolar disorder, schizophrenia, and adjustment disorder. The study suggests that isotretinoin may confer a lower risk of several psychiatric comorbidities.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2023)
Letter
Dermatology
Katharina Boch, Henner Zirpel, Diamant Thaci, Noor Mruwat, Detlef Zillikens, Ralf J. Ludwig, Khalaf Kridin
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Review
Immunology
Katja Bieber, Jennifer E. Hundt, Xinhua Yu, Marc Ehlers, Frank Petersen, Christian M. Karsten, Jorg Koehl, Khalaf Kridin, Kathrin Kalies, Anika Kasprick, Stephanie Goletz, Jens Y. Humrich, Rudolf A. Manz, Axel Kuenstner, Christoph M. Hammers, Reza Akbarzadeh, Hauke Busch, Christian D. Sadik, Tanja Lange, Hanna Grasshoff, Alexander M. Hackel, Jeanette Erdmann, Inke Koenig, Walter Raasch, Mareike Becker, Anja Kerstein-Staehle, Peter Lamprecht, Gabriela Riemekasten, Enno Schmidt, Ralf J. Ludwig
Summary: Approximately 5% of the world-wide population is affected by autoimmune diseases, which are still difficult to treat and have a significant economic impact. The progression from harmless to inflammatory autoimmune disease conditions is a key factor. Biomarkers that can predict this progression would be highly impactful. Factors such as genetics, environment, and lifestyle choices may influence the progression from benign to inflammatory autoimmune conditions. Research is needed to define and modulate autoimmune predisease.
AUTOIMMUNITY REVIEWS
(2023)
Article
Dermatology
Khalaf Kridin, Ralf J. Ludwig
Summary: Isotretinoin does not increase the risk of Crohn's disease, but it may be associated with a slight and temporary increase in the risk of ulcerative colitis. However, it can lower the risk of irritable bowel syndrome.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2023)
Letter
Dermatology
Khalaf Kridin, Noor Mruwat, Diamant Thaci, Ralf J. Ludwig
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Review
Veterinary Sciences
Veronika Hartmann, William V. J. Hariton, Siavash Rahimi, Christoph M. Hammers, Ralf J. Ludwig, Eliane J. Mueller, Jennifer E. Hundt
Summary: Pemphigus is a severe autoimmune bullous disease that targets adhesion proteins desmoglein 3 and/or desmoglein 1. Current treatment involves systemic immunosuppression, and drug development focuses on B cells, autoantibodies, and tissue pathology. A human skin organ culture (HSOC) model has been established as an alternative to animal models for studying pemphigus, replicating key features of the disease.
LABORATORY ANIMALS
(2023)
Article
Dermatology
Khalaf Kridin, Noor Mruwat, Ralf J. Ludwig
Summary: Patients with pemphigus who were treated with rituximab had a lower risk of long-term cardiovascular and metabolic outcomes compared with those receiving first-line corticosteroid-sparing agents. Rituximab may be particularly preferred in patients with preexisting cardiovascular and metabolic risk factors.
Article
Immunology
Khalaf Kridin, Artem Vorobyev, Cristian Papara, David A. De Luca, Katja Bieber, Ralf J. Ludwig
Summary: Identification of risk factors and sequelae of diseases is crucial for primary prevention and disease management. This study used TriNetX to identify risk factors and sequelae of the rare autoimmune disease EBA. The findings revealed chronic inflammatory diseases, especially lupus erythematosus and lichen planus, as the highest risk factors for EBA development and metabolic and cardiovascular diseases, and thrombosis as the most common sequelae after EBA diagnosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yask Gupta, Anna Lara Ernst, Artem Vorobyev, Foteini Beltsiou, Detlef Zillikens, Katja Bieber, Simone Sanna-Cherchi, Angela M. M. Christiano, Christian d D. Sadik, Ralf j J. Ludwig, Tanya Sezin
Summary: In this study, 591 mice were used to demonstrate that fungi are regulated by host genetics and that diet has a regulatory role in the composition of gut fungi. The role of fungi in complex interactions involving host genetics, bacteria, and environmental factors remains understudied. Using whole genome sequencing and genotyping, quantitative trait loci associated with various fungal species were mapped in mice. Additionally, the study identified fungal indicator species associated with different dietary regimes.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Immunology
Jennifer E. Hundt, Markus H. Hoffmann, Kyle T. Amber, Ralf J. Ludwig
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Maria Shoykhet, Orsela Dervishi, Philipp Menauer, Matthias Hiermaier, Sina Moztarzadeh, Colin Osterloh, Ralf J. Ludwig, Tatjana Williams, Brenda Gerull, Stefan Kaab, Sebastian Clauss, Dominik Schuettler, Jens Waschke, Sunil Yeruva
Summary: Arrhythmogenic cardiomyopathy (AC) is a familial heart disease caused by impaired desmosome turnover, and stabilizing desmosome integrity through EGFR and ROCK inhibition may offer new treatment options. In this study, EGFR inhibition enhanced cardiomyocyte cohesion and increased DSG2 recruitment and binding at cell borders. Additionally, EGFR inhibition led to the upregulation of ROCK, and ROCK inhibition abolished the effects of EGFR inhibition on desmosome assembly and cardiomyocyte cohesion. These findings suggest that targeting EGFR and ROCK could be potential therapeutic strategies for AC.
Article
Biochemistry & Molecular Biology
Ulrike Raap, Maren M. M. Limberg, Khalaf Kridin, Ralf J. J. Ludwig
Summary: Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized by autoantibodies targeting structural proteins. Pruritus is common in patients with BP and pemphigus, and can be the sole symptom in some cases. The temporal relationship between pruritus and AIBDs is unclear, and the presence of pruritus in other AIBDs is also unknown.
Article
Dermatology
Ralf J. Ludwig, Esther von Stebut
Summary: The epidemiology and clinical presentation of inflammatory dermatoses vary considerably between people with different colors of skin. It is important to know the epidemiology and recognize key clinical characteristics of these diseases in patients with skin of color (SOC) in order to provide excellent dermatological care for all patients.
Article
Dermatology
Stefan Tukaj, Katja Bieber, Wiebke Pruessmann, Jasper N. Pruessmann, Enno Schmidt, Detlef Zillikens, Ralf J. Ludwig, Michael Kasperkiewicz
Summary: Healthy individuals with BP autoantibody reactivity have abnormal vitamin D levels and a specific cytokine profile.
ARCHIVES OF DERMATOLOGICAL RESEARCH
(2023)
Article
Dermatology
Khalaf Kridin, Keren Lyakhovitsky, Erez Onn, Anna Lyakhovitsky, Ralf Ludwig, Orly Weinstein, Arnon D. Cohen
Summary: There is a bidirectional association between vitiligo and psoriasis.
ARCHIVES OF DERMATOLOGICAL RESEARCH
(2023)
