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
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)
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
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
Medicine, General & Internal
Hannah Zillikens, Anika Kasprick, Colin Osterloh, Natalie Gross, Michael Radziewitz, Cindy Hass, Veronika Hartmann, Martina Behnen-Harer, Nancy Ernst, Katharina Boch, Gestur Vidarsson, Remco Visser, Tamas Laskay, Xinhua Yu, Frank Petersen, Ralf J. Ludwig, Katja Bieber
Summary: Class I phosphoinositide 3-kinases (PI3K) are involved in the pathogenesis of experimental epidermolysis bullosa acquisita (EBA), affecting disease progression by influencing neutrophil activation. Selective inhibition of different PI3K isoforms can impact clinical manifestations of EBA, with topical inhibition of PI3K beta identified as a potential therapeutic target for the treatment of EBA.
FRONTIERS IN MEDICINE
(2021)
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
Genetics & Heredity
Sarah Kiener, Heather Troyer, Daniel Ruvolo, Paula Grest, Sara Soto, Anna Letko, Vidhya Jagannathan, Tosso Leeb, Elizabeth A. Mauldin, Ching Yang, Ana Rostaher
Summary: Epidermolysis bullosa (EB) is a heterogeneous disease characterized by defective adhesion of the epidermis to the dermis. This study identified COL17A1 gene variants as the cause of EB in two cats, providing new insights into the diagnosis and genotype-phenotype correlation of this disease.
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)
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
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)
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)
Review
Dermatology
Emma Hignett, Naveed Sami
Summary: Epidermolysis bullosa acquisita (EBA) is a rare acquired autoimmune blistering skin disorder that mainly affects adults. This review identified and reported clinical features and course of 40 pediatric EBA cases, with mucosal tissues being affected in the majority of cases. Treatment typically consists of systemic corticosteroid combined with dapsone, and prognosis is generally favorable with most cases achieving remission or control with therapy. Childhood EBA should be considered in the diagnosis of pediatric blistering diseases despite its rarity.
PEDIATRIC DERMATOLOGY
(2021)
Article
Medicine, General & Internal
Maximilian Kueckelhaus, Tobias Rothoeft, Laura De Rosa, Burcu Yeni, Tobias Ohmann, Christoph Maier, Lynn Eitner, Dieter Metze, Lorena Losi, Alessia Secone Seconetti, Michele De Luca, Tobias Hirsch
Summary: This study reports long-term clinical outcomes in a child with a severe genetic skin disease who received genetically corrected autologous epidermal cultures.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Agriculture, Dairy & Animal Science
Sarah Kiener, Elizabeth A. Mauldin, Vidhya Jagannathan, Margret L. Casal, Tosso Leeb
Summary: Epidermolysis bullosa (EB) is a group of blistering disorders caused by pathogenic variants in multiple genes. This study identified the causative variant, KRT5:p.(E476K), through investigating a puppy with typical clinical signs of EB.
Article
Immunology
Giovanni Di Zenzo, Giovanna Floriddia, Sabrina Rossi, Feliciana Mariotti, Alessia Primerano, Angelo Giuseppe Condorelli, Biagio Didona, Daniele Castiglia
Summary: This study reports a case of a patient with hereditary epidermolysis bullosa (EB) who also developed an autoimmune response to basement membrane components. Diagnosis of bullous pemphigoid (BP) was confirmed by detecting antibodies in the patient's skin and serum. Corticosteroid therapy led to remission of BP manifestations. EB patients presenting rapid disease worsening should be investigated for the development of a concomitant autoimmune blistering disease.
FRONTIERS IN IMMUNOLOGY
(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)
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.
Review
Medicine, General & Internal
Cristian Papara, David A. De Luca, Katja Bieber, Artem Vorobyev, Ralf J. Ludwig
Summary: Morphea, also known as localized scleroderma, is a chronic inflammatory connective tissue disorder that affects both adults and children. It is characterized by inflammation and fibrosis of the skin and underlying soft tissue, and in certain cases, can also affect surrounding structures. The etiology of morphea is still unknown, but genetic predisposition, vascular dysregulation, T(H)1/T(H)2 imbalance, cytokines, and certain environmental factors may contribute to its development. Proper assessment of disease activity and prompt initiation of treatment are crucial to prevent permanent damage.
FRONTIERS IN MEDICINE
(2023)
Review
Medicine, General & Internal
David A. De Luca, Cristian Papara, Artem Vorobyev, Hernan Staiger, Katja Bieber, Diamant Thaci, Ralf J. Ludwig
Summary: Lichen sclerosus (LS) is an inflammatory mucocutaneous condition primarily affecting postmenopausal women, with unknown etiology. LS is associated with factors such as hormonal status, trauma, and autoimmune diseases. LS pathogenesis involves genetic predisposition, immune-mediated mechanisms, tissue remodeling genes, and oxidative stress. LS presents as chronic whitish atrophic patches with itching and soreness in the genital and anal regions. Treatment options include topical corticosteroids and calcineurin inhibitors. LS is a common dermatological disease with an incompletely understood pathogenesis and limited treatment options.
FRONTIERS IN MEDICINE
(2023)
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)
