Study on the characteristics of drug-induced liver damage presenting with dermatological reactions

Home Page » News » Study on the characteristics of drug-induced liver damage presenting with dermatological reactions

The study involves researchers from IBIMA Plataforma BIONAND, the University of Malaga and the Virgen de la Victoria University Hospital.

Drug-induced liver injury (DILI) is a significant problem in modern medicine, as it can occur as a result of the use of a wide variety of drugs, with symptoms ranging from mild symptoms such as nausea or fatigue to much more serious conditions such as jaundice or fulminant liver failure, among others. It is a challenge for the scientific community to understand the underlying mechanisms in order to develop more effective strategies to prevent, diagnose and treat these sometimes potentially serious complications.

Researchers from the Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), the Hospital Universitario Virgen de la Victoria, and the University of Málaga, within the framework of the European Cooperation in Science and Technology (COST) network ‘Prospective European Drug-Induced Liver Injury Network, Pro Euro DILI Network’, which is led by the Institute, with the participation of 24 countries, have carried out a study published in the journal ‘.Archives of Toxicology’ where the clinical features, clinical outcome and the main drugs involved in DILI associated with eosinophilia and systemic symptoms (DRESS) have been investigated.

A percentage of DILI cases may present severe dermatological reactions. The cases analysed in the present study, included in two prospective registries (Spanish Hepatotoxicity Registry and Latin American Hepatotoxicity Registry), were classified as DILI-DRESS cases, which were characterised by skin lesions and, in a high percentage, eosinophilia, which is an abnormal increase in a type of white blood cell called an eosinophil that can occur in response to certain medical conditions or allergic reactions.

The team of researchers who carried out this study belong to the group ‘Hepatogastroenterology, Pharmacology and Translational Clinical Therapeutics’, led by professionals from the Hospital Universitario Virgen de la Victoria and professors from the University of Malaga, Raúl J. Andrade and María Isabel Lucena. Dr. Andrade is also head of the Digestive System Service at the Hospital Universitario Virgen de la Victoria.

Within this research group, Ismael Álvarez, has specifically led this study, pointing out that it is ‘crucial to understand certain drugs that can affect the liver in different ways’, which is why he has assured that ‘thanks to this study, possible specific patterns of liver injury and risk factors associated with the DILI-DRESS clinical phenotype were identified, which will help to improve early identification and treatment of this condition’.

The results revealed that patients with DILI-DRESS more frequently presented with cholestatic/mixed liver damage - meaning problems with bile flow complications from the liver - and tended more frequently to require hospitalisation for a more severe clinical course than those patients with DILI without severe dermatological reactions.

In addition, distinctive patterns of causal drugs were identified, with antiepileptics as the most commonly associated drug class.

Inmaculada Medina, a researcher in the same research group, said that ‘the fact that antiepileptic drugs are the most frequent cause of DILI-DRESS in our cohort is significant,’ she said, noting that this fact ‘suggests the importance of closely monitoring patients receiving these drugs and being alert to possible si

In addition, the study also found that higher total bilirubin levels and the absence of eosinophilia were associated with an increased risk of worse prognosis in patients with DILI-DRESS. These findings reinforce the importance of early detection and proper management of this condition.

The team that conducted the study said they are committed to further advancing the understanding of drug-induced liver injury in order to improve the safety and efficacy of medical treatments and have a direct impact on patients' health, wellbeing and quality of life.

Dr. García Martín began her scientific career in the field of magnetic resonance imaging applied to biomedical research. In recent years, her research activity has been focused on nanotechnology applied to health. She completed her Ph.D. at the Sols-Morreale Biomedical Research Institute in Madrid (IIBM, CSIC), complementing her training with fellowships at several institutions in Europe and the United States of America. After completing her Ph.D., she joined the University of Arizona Cancer Center as a postdoctoral researcher, where she worked for three years until her return to the IIBM as a Ramón y Cajal researcher.

In 2011, she joined the Andalusian Center for Nanomedicine and Biotechnology (BIONAND)—now IBIMA Plataforma BIONAND—as leader of the Biomedical Magnetic Resonance Laboratory (BMRL) group, accredited by the Andalusian Agency of Knowledge as a consolidated group in the Andalusian Plan for Research, Development, and Innovation (PAIDI). From 2014 to 2019, she held the position of Deputy Chief Scientific Officer at BIONAND. She is currently the coordinator of the Nanodiagnostics Area at IBIMA Plataforma BIONAND and the scientific manager of the Nanoimaging Unit, a multimodal imaging platform accredited as a Singular Scientific and Technological Infrastructure (ICTS) by the Ministry of Science and Innovation as an independent hub of the ICTS NANBIOSIS.

Her current lines of research focus on the development of magnetic nanoparticles and other nanosystems for the diagnosis and treatment of tumors with special emphasis on malignant brain tumors and, on the other hand, the identification of metabolic biomarkers for the diagnosis and prognosis of various diseases, mainly cancer and neurodegenerative diseases, using NMR-based metabolomics.

Dr. Matas Rico earned a Ph.D. in biology from the University of Málaga in 2009 and trained for more than ten years at the prestigious Netherlands Cancer Institute research center in Amsterdam (The Netherlands). She was awarded the Ramón y Cajal program from the Ministry of Science, Innovation, and Universities in 2019 and became a permanent professor of the Department of Cell Biology, Genetics, and Physiology of the University of Málaga in 2024.

She is co-lead researcher of the Translational Research in Genitourinary Oncology group, with extensive experience in cell signaling pathways and their clinical impact. Her line of research focuses on the study of signaling pathways relevant to cancer progression, metastasis, and immunology. She has received funding from the Ministry of Science and Innovation and the Spanish Association Against Cancer Foundation. The results of her research have had great repercussion in the field of cancer cell biology and have been published in high impact factor journals such as ‘Cancer Cell,’ ‘Cell Reports,’ ‘Trends in Cancer,’ and ‘eLife,’ among others. In the research group, she participates in several clinical trials on urothelial bladder cancer. She is also a project assessor for the State Research Agency and the Spanish Association Against Cancer Foundation and participates in the review of articles and on different scientific evaluation committees.

As a lecturer at the University of Málaga, she teaches courses for the bachelor's degree in biology and biochemistry program; is a professor in the advanced biotechnology Ph.D. program; and supervises undergraduate, master's, and Ph.D. students.

Contact: elisa.matas@ibima.eu

Dr. Moreno Dueñas has been a full professor at the University of Málaga in the Department of Systems Engineering and Automation since 2023. He began his academic career with a bachelor's degree in telecommunication engineering from the University of Málaga in 2007 and a Ph.D. in mechatronics from the same institution in 2015.

He has worked in the Machine Perception and Intelligent Robotics Lab (MAPIR) group of the institute and the University of Málaga since 2006. He is currently co-lead investigator of the group, conducting projects focused on mobile robotics, computer vision, and artificial perception.

During his predoctoral career, he completed a research fellowship at the University of Bristol (2011) and collaborated with a research project at the University of Lincoln (2013), both in the United Kingdom. During these international experiences, he worked on the analysis and automatic description of images and the development of perception systems for agriculture, significantly influencing his doctoral work and subsequent research.

In regard to his scientific production, he has published 23 articles in ISI-JCR indexed journals and has made more than 20 contributions at conferences. Among his outstanding publications are articles on perception systems for mobile robots and widely cited multisensory datasets. He has also collaborated with other groups at the institute to develop systems for the automatic analysis and tracking of human movement, which resulted in the publication of a series of articles.

At the international level, he has participated in several European projects, especially those focused on support robotics for older adults and navigation systems for robots inside houses as well as on funded national projects on similar topics.

Dr. García Ranea is a professor at the Department of Molecular Biology and Biochemistry of the University of Málaga. From 1997 to 2001, he completed his Ph.D. degree in bioinformatics at the National Centre for Biotechnology (CNB-CSIC-Madrid). After a brief postdoctoral period at the National Centre for Biotechnology, he was subsequently hired in 2002 as a senior doctoral researcher at the University College London, where he worked until 2008, when he joined the University of Málaga as a Ramón y Cajal Researcher. He is a researcher at the Rare Diseases Networked Research Center (CIBERER-ISCIII), scientific coordinator of the Bioinformatics Common Research Support Service (ECAI) of the Biomedical Research Institute of Málaga (IBIMA), and leader of the National Institute of Bioinformatics (INB-ELIXIR) hub in Málaga. His research currently focuses on the areas of bioinformatics and systems biology applied to biomedicine and personalized precision medicine, with special attention to the study of rare diseases. He has authored more than 70 scientific publications in high impact journals; served as principal investigator on six national projects, three projects of excellence of the Regional Government of Andalusia, two European projects, and other projects; and holds contracts with universities, private foundations, and industry. In addition to serving as principal investigator on the aforementioned projects, he has also collaborated on more than 20 projects funded at regional, national, and European level during his professional career.

The research group he currently leads has experience in the prediction and modeling of complete interactomes and specific subnetworks based on biocomputational methods as well as on the use of these networks in the study of the molecular systems underlying the functioning of cellular systems and their implication in diseases. He also works on the modeling of drug-protein networks in order to generate hypotheses for compound repositioning as well as to predict the side effects and adverse effects of drugs. The group has an extensive track record working on the prediction of rare syndromes in patients and investigating the relationship between diseases and the mutations that produce them through the development and implementation of different workflows for the analysis and integration of multiomics data, with outstanding experience in the analysis of transcriptomic data.

Contact: ranea@uma.es

Dr. Mena Vázquez received her medical degree from the University of Málaga in 2010 and her Ph.D. from the University of Málaga in 2016. She has been a specialist physician in the Rheumatology Department at the Rheumatology Clinical Unit of the Regional University Hospital of Málaga since 2016 and has been Section Chief of the Rheumatology Clinical Unit at the Regional University Hospital of Málaga since 2021. In addition, she is co-lead researcher of the institute’s Inflammatory and Autoimmune Diseases research group, a member of the PAIDI CTS-1034 inflammatory rheumatic diseases study group since 2017, a collaborator in the Research Network on Rheumatic Diseases, collaborator in the Cooperative Research Networks Aimed at Health Outcomes, clinical coordinator of the Andalusian Research Network for Research on Rheumatic Diseases, and coordinator of the Research Unit of the Regional University Hospital of Málaga. She is a member and leader of the Spanish Society of Rheumatology research commission.

In addition, she has been a clinical tutor since 2014 and an honorary collaborator at the University of Málaga School of Medicine since 2020. She has research experience with previous contracts equivalent to the Juan Rodés contracts from 2018–2020, was the principal investigator for seven nationally competitive projects, and was a collaborator on more than ten projects. She participates as principal investigator in five clinical trials and collaborates on more than 40 clinical trials in phases II, III, and IV at the Immunologically-Mediated Diseases Research Unit.

In terms of scientific quality indicators, she has authored 66 publications since 2016, leading 45 of them. In addition, she has contributed to 21 other publications not as a leader. She has made more than 150 communications to conferences, edited of scientific article and a treatise on rheumatic diseases for the Spanish Society of Rheumatology, participated in six book chapters, and holds three patents. She has supervised seven medical degree final projects, two master’s degree final projects, and four doctoral theses. She also supervises researchers during their training

Contact: natalia.mena.sspa@juntadeandalucia.es

Dr. Moreno Peral holds a bachelor’s degree and Ph.D. in psychology from the University of Málaga. She is co-lead researcher of the Mental Health, Services, and Primary Care (SAMSERAP) group. Her lines of research focus on the prevention of depression and anxiety, the development of risk algorithms, and the use of information technology for personalized mental health interventions. She has published multiple articles in high impact journals, including studies on risk factors for anxiety disorders and the effectiveness of psychological and educational interventions.

In terms of research projects, has led projects such as “PrevANS,” focused on the prevention of anxiety and depression through personalized interventions based on risk algorithms and decision support system technologies.

On the international level, she participates in European networks such as the European Cooperation in Science & Technology (COST) for the study of perinatal depression and individualized psychotherapeutic treatments for young people. She has received several awards for her research work throughout her professional career. She is group leader for projects funded by the Ministry of Science, Innovation, and Universities.

Contact: patriciamorenoperal@uma.es

Dr. Bernal López earned her Ph.D. in biochemistry and molecular biology in 2002. She participated in the Miguel Servet Program of the Carlos III Institute of Health (2015–2023) and the Nicolás Monardes Program (2021) of the Andalusian Health Service. Since 2006, she has served as research coordinator of the Internal Medicine Clinical Unit of the Regional University Hospital of Málaga and professional tutor for the Advanced Vocational Training Course for Clinical Diagnosis Laboratory Technicians. In addition, she is an evaluator for national and international projects, including the Health Research Fund (FIS) and the National Agency for the Promotion of Science and Technology (FONCyT-ANPCyT).

She is co-lead investigator of the Research on Diabetes, Obesity, and Vascular Risk Factors group. Systemic Autoimmune Diseases and principal investigator for the Pathology of Atherosclerosis, Diabetes, and Obesity Group (CTS1023) of the Andalusian Research Plan. Furthermore, she has been a member of the Pathophysiology of Obesity and Nutrition Networked Research Center (CIBER) of the Carlos III Institute of Health since 2007.

Internationally, she has been a professional mentor for European medical students completing extracurricular internships at the University of Málaga. She has published more than 126 original articles in her line of research on diabetes, obesity, and cardiovascular risk factors. She has supervised seven doctoral theses in the last seven years. In regard to projects, she has led 16 national or regional projects and collaborated on 32 and has participated in six international projects. She has also coordinated 22 multicenter clinical trials on diabetes, obesity, and cardiovascular risk factors and holds two patents under evaluation.

Dr. Gómez Huelgas has been Chief of the Internal Medicine Clinical Unit of the Regional University Hospital of Málaga since 2005 and is a full professor at the Department of Medicine and Dermatology at the University of Málaga School of Medicine. In addition, he was President of the Spanish Society of Internal Medicine from 2017 to 2020 and is currently President of the European Federation of Internal Medicine. He is an associate researcher at the Pathophysiology of Obesity and Nutrition Networked Research Center (CIBER) and lead researcher of the Diabetes, Obesity, and Other Vascular Risk Factors. Systemic Autoimmune Diseases group.

On the international level, he is a national expert representative of the Joint Actions convened in the 2016 working plan of the European Directorate-General for Health and Consumers’ Third Health Programme.

He is the author of more than 160 original publications and participates in 13 national and two international projects. In addition, he participates in 18 multicenter clinical trials on diabetes, hyperlipidemia, and obesity and serves as coordinator for five of them. He has given more than 200 communications at regional and national conferences and more than one hundred communications at international conferences.

After completing her bachelor’s degree in biology in 2008, Dr. García Caballero completed a Ph.D. at the University of Málaga in which she focused on the search for new antiangiogenic and antitumor compounds. The results were included in a total of eight scientific articles and two book chapters. In addition, her collaboration with various pharmaceutical companies have led to four patents. She continued her training as a Marie Skłodowska-Curie researcher at the GIGA-Cancer GIGA-Cancer and the University of Liège (Belgium), where she developed a murine model for the study of lymphatic metastasis and characterized several inhibitors of the lymphangiogenic process. Subsequently, in 2017, she joined the Center for Cancer Biology and the Catholic University of Leuven (Belgium), where she completed her second postdoctoral fellowship focused on the study of endothelial metabolism.

In 2021, she joined the University of Málaga as a Beatriz Galindo Distinguished Researcher and Professor. She currently leads a research team at IBIMA Plataforma BIONAND, supervising several postdoctoral researchers, Ph.D. students, and master’s degree students. In addition, she teaches in the bachelor’s degree programs in biochemistry, biology, and chemistry and in the master’s degree in molecular and cellular biology program at the University of Málaga. She is co-author of more than 50 publications, most of which have been published in very high impact factor journals (Nature, Cell, Cell Metabolism, Cancer Cell, Nature Communications, Developmental Cell, Circulation Research, etc.). She is also an editor of two international journals, a scientific reviewer, participates in evaluation committees and panels, and has received 16 awards during her career.

Contact: melissa@uma.es

Dr. Serrano Criado has been working as a principal investigator at the institute through the Miguel Servet program and, since May 2023, as a researcher through the Nicolás Monardes program at the Mental Health Clinical Unit of the Regional University Hospital of Málaga. She has served as co-lead researcher of the Neuropsychopharmacology group and coordinator of Area 3: Neurosciences, Chronicity, Aging, and Health in Vulnerable Populations. Her lines of research focus on the characterization of lipid mediators in addictive disorders and comorbid mental illnesses through translational studies with the aim of identifying biomarkers and describing underlying molecular processes.

She has directed five national projects and one regional project and has participated in numerous national and international projects resulting in 137 scientific publications. She has also coauthored book chapters and presented numerous contributions at conferences. In addition, she has experience coordinating and tutoring students and technical staff and has collaborated on thesis committees, reviews for scientific journals, and the evaluation of national and international projects. She forms part of several stable research networks and structures, including the Research Network on Primary Care for Addictions (RIAPAd) and COST Action CA22111.

Contact: antonia.serrano@ibima.eu

Dr. Mayorga is a senior researcher through the Miguel Servet II, Nicolás Monardes, and Consolida programs. She works at the Allergology Clinical Unit of the Regional University Hospital of Málaga and the institute. She is coordinator of the research laboratory at the Civil Hospital of Málaga and co-lead researcher of the Allergic Diseases to Drugs and Allergens Research Group, recognized as a Center of Excellence by the World Allergy Organization (WAO). In addition, she is a founding member of Bioherent, a spin-off of the University of Málaga. In 2023, she was appointed a Fellow of the European Academy of Allergy and Clinical Immunology (EAACI).

Her research career focuses on the immunological mechanisms of adverse drug reactions and the improvement of in vitro tests as well as the identification of biomarkers in immunotherapy for food and respiratory allergies. She belongs to the Basic and Clinical Immunology Committee of the EAACI and the Spanish Society of Allergology and Clinical Immunology (SEAIC). She also participates in several European consortia, including EUROBAT and COST Action TD0802. She has been principal investigator for 18 projects and has collaborated in European projects such as AllerScreening and DIFAMEM. Her work has resulted in more than 250 publications in high impact journals and ten patents. In addition, she has directed 14 doctoral theses and supervises researchers in training. She is accredited as a full professor by ANECA.

Contact: lina.mayorga@ibima.eu

Dr. Yahyaoui Macías is a specialist in Clinical Biochemistry at the Regional University Hospital of Málaga and has been head of the Metabolopathies Laboratory and the Neonatal Screening Center of Eastern Andalusia since 2009. She has completed two training fellowships abroad at the Mayo Clinic and at the Connecticut Department of Public Health, specializing in advanced neonatal screening techniques. In 2021, she took on the role of healthcare coordinator of the Diagnostic and Treatment Unit for Congenital Metabolic Diseases at the Regional University Hospital of Málaga, which seeks to be designated a Reference Center, Department, or Unit (CSUR). In addition, she participates on the advisory group of the Andalusian Strategy for Personalized Precision Medicine and has coordinated line 2 of the new Andalusian Care Plan for Individuals with Rare Diseases (PAPER). She has been deputy coordinator of IBIMA-Rare since 2021. She has served as chief of the Clinical Analysis Department of the Regional University Hospital of Málaga since March 2024.

She has been a member of the Expert Panel on Newborn Screening of the Clinical Laboratory and Standards Institute (CLSI), contributing to the creation of clinical guidelines and international standards for neonatal screening. She has done research on the identification of new biomarkers in neonatal screening and the development of new technology for inherited metabolic diseases. In addition, she has received several awards and competitive research grants and has published more than 40 scientific articles, participated in more than 20 research projects, and supervised two doctoral theses at the University of Málaga.

Contact: raquel.yahyaoui.sspa@juntadeandalucia.es

Dr. Cuesta Vargas is a full professor at the University of Málaga, accredited as a dean by ANECA in 2022. He has 23 years of professional experience as a physical therapist. He has spent more than 15 years as a full-time teaching and research staff member (PDI) at the University of Jaén and the University of Málaga and 12 years at the Queensland University of Technology (Australia). He has published more than 250 contributions in JCR journals. He has codirected 29 doctoral theses and 75 master’s theses in the last ten years, leading the Clinimetry Research Group at the institute. In addition, he is part of the Research Network on Preventive Activities and Health Promotion (REDIAPP), funded by ISCIII from 2007 to 2020, and is principal investigator of the FUNNEL+ project, funded by ISCIII, and the iGAME project, funded by the European Union’s Horizon 2020 program.

He has been highly involved in education in the last ten years, teaching a total of 2,550 hours of undergraduate and 2,590 hours of postgraduate courses. He received the Educa-Abanca prize for the best teacher in Spain in the university category (all areas, 4th place) and is editor-in-chief of the journal BMC Sports Science, Medicine and Rehabilitation.

He currently focuses on the research, development, and transfer of clinical aspects related to human movement. His research ranges from the validation of indexes to the implementation of dashboards for clinical decisions to the transfer of therapeutic exercise programs that have a high impact on chronic conditions. This research incorporates the most advanced scientific methodology on the biomechanics, physiology, psychometrics, and epidemiology of physical therapy. He was included in the Stanford 2022 and 2023 lists of the top 2% of the world’s most influential scientists in the area of clinical medicine, based on citations for his scientific contributions over the past 25 years..

Contact: acuesta@uma.es

Dr. González is a Full Professor at the University of Málaga in the Department of Cell Biology, Genetics, and Physiology at the University of Málaga, a department she joined in 2016 through the prestigious Ramón y Cajal program of the State Research Agency. She is also the lead researcher of the Cellular Reprogramming and Cellular Models for Biomedical Applications group at IBIMA Plataforma BIONAND. She holds a bachelor’s degree in biology from the University of Seville and a Ph.D. in biomedicine from the University of Barcelona.

She has completed postdoctoral fellowships nationally, at the Institute for Biomedical Research of Barcelona, and internationally, at the Department of Neurosurgery of the University of California San Francisco, where she studied the role of the asymmetric division of cancer stem cells in oligodendriomas, as well as at Michigan State University, where she investigated cell reprogramming. A notable result of the latter was her article in Science on human oocyte factors and pluripotency.

She has been leading projects at the institute since 2016, including studies on multiple sclerosis, with recent publications. Her main line of research focuses on epigenetic phenomena during cellular reprogramming as well as their use to generate cellular models of disease, with funding from the Plan Retos of the Ministry of Economy, Commerce, and Companies; the Regional Ministry of Universities, Research, and Innovation; and the University of Málaga. Accredited by the I3 program, she has supervised ten master’s students and is supervising two Ph.D. students. She is a member of research ethics committees in Andalusia and collaborates with several national and international groups on cellular and biomedical research. She has published more than 22 international scientific publications of impact in JCR journals and has led six competitive research projects in the last five years.

Contact: egonmu@uma.es

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Study on the characteristics of drug-induced liver damage presenting with dermatological reactions

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