A rapid action plan to improve diagnosis and management of lipodystrophy syndromes

IntroductionLipodystrophy syndromes are rare diseases that can present with a broad range of symptoms. Delays in diagnosis are common, which in turn, may predispose to the development of severe metabolic complications and end-organ damage. Many patients with lipodystrophy syndromes are only diagnosed after significant metabolic abnormalities arise. Prompt action by clinical teams may improve disease outcomes in lipodystrophy syndromes. The aim of the Rapid Action Plan is to serve as a set of recommendations from experts that can support clinicians with limited experience in lipodystrophy syndromes.MethodsThe Rapid Action Plan was developed using insights gathered through a series of advisory meetings with clinical experts in lipodystrophy syndromes. A skeleton template was used to facilitate interviews. A consensus document was developed, reviewed, and approved by all experts.ResultsLipodystrophy is a clinical diagnosis. The Rapid Action Plan discusses tools that can help diagnose lipodystrophy syndromes. The roles of clinical and family history, physical exam, patient and family member photos, routine blood tests, leptin levels, skinfold measurements, imaging studies, and genetic testing are explored. Additional topics such as communicating the diagnosis to the patients/families and patient referrals are covered. A set of recommendations regarding screening and monitoring for metabolic diseases and end-organ abnormalities is presented. Finally, the treatment of lipodystrophy syndromes is reviewed.DiscussionThe Rapid Action Plan may assist clinical teams with the prompt diagnosis and holistic work-up and management of patients with lipodystrophy syndromes, which may improve outcomes for patients with this rare disease

A real-world pharmacovigilance assessment and literature review of lymphoma development in lipodystrophy

IntroductionMetreleptin is a form of leptin replacement therapy used with diet and lifestyle modifications to treat the metabolic complications of leptin deficiency in lipodystrophy, a rare disease characterized by adipose tissue deficiency. Previously, identification of T-cell lymphomas in three metreleptin-treated patients with acquired generalized lipodystrophy (AGL) suggested a possible relationship between metreleptin and lymphoma development. To further investigate this, we performed a real-world pharmacovigilance assessment and literature review to identify lymphomas in patients with lipodystrophy and congenital leptin deficiency (CLD) who were either metreleptin-naïve, or who had previously received/were receiving metreleptin at the time of lymphoma diagnosis.MethodsCases were identified from PubMed, Embase and the Cochrane Library (from database inception through to November 22, 2024), and through review of 11 years post-marketing data from the global safety database (GSD) of the marketing authorization holder for metreleptin.ResultsThe final analysis set comprised 17 lymphomas in 16 patients reported in 11 published articles and one GSD case report. Twelve lymphomas were recorded in 12 metreleptin-naïve patients — these comprised six T-cell lymphomas (one each in six patients with AGL), three B-cell lymphomas (in two patients with familial partial lipodystrophy and one patient with AGL), and three Hodgkin lymphomas (separately reported in one patient each with generalized lipodystrophy, juvenile-onset dermatomyositis-associated lipodystrophy, and CLD). Five lymphomas were identified in four metreleptin-treated patients, three of whom (all with AGL and T-cell lymphomas) were reported in previously published studies. The remaining metreleptin-treated patient (from the GSD) had generalized lipodystrophy-associated atypical progeroid syndrome and developed a B-cell lymphoma and brain lymphoma following solid organ transplantation and immunosuppressant therapy. All nine T-cell lymphomas occurred in patients with AGL, and additional autoimmune and/or inflammatory disorders were commonly reported in these patients.DiscussionWhile a contributory role for metreleptin in lymphoma development in patients with lipodystrophy cannot be excluded, our analysis suggests that lymphoma development may be associated with underlying pathophysiology that also leads to lipodystrophy rather than the pharmacological actions of metreleptin. Our findings support the view that, in some instances, immunoproliferative disorders of T-cells may contribute to syndromes involving autoimmune processes, including AGL

European lipodystrophy registry: background and structure

Abstract: Background: Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with lipodystrophy. Results: The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of lipodystrophy (with the exception of HIV-associated lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, Münster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years. Conclusions: A European registry for all patients with lipodystrophy will provide a platform for improved research in the area of lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with lipodystrophy are invited to participate in the ECLip Registry. Study registration: ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered

European lipodystrophy registry: background and structure

Abstract: Background: Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with lipodystrophy. Results: The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of lipodystrophy (with the exception of HIV-associated lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, Münster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years. Conclusions: A European registry for all patients with lipodystrophy will provide a platform for improved research in the area of lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with lipodystrophy are invited to participate in the ECLip Registry. Study registration: ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered

Neurosyphilis in Psychiatric Settings: Three Case Reports

WOS: 000398584900008Syphilis is a generally sexually transmitted and multisystem disease caused by the spirochete Treponema pallidum. All of the organs of the body may be involved during the course of the disease. Neurosyphilis is a clinical form of syphilis with the central nervous system (CNS) involvement. While primarily meningeal and vascular structures are involved in early neurosyphilis, a parenchymal affection of the brain and spinal cord emerges at later stages of neurosyphilis. It presents with symptoms of meningitis, meningovasculitis and parenchymal neurosyphilis (presenting as tabes dorsalis and general paresis). Clinically, it can mimic a variety of psychiatric disorders such as depression, psychosis, mania, delirium, personality changes and dementia. During its progression making presentations similar to many systemic or neuropsychiatric diseases, syphilis is defined as "great imitator". Nowadays, neurosyphilis is a rare disease as a result of the widespread use of antibiotics that must be kept in mind in the differential diagnosis of neurological and psychiatric disorders. In this article, three neurosyphilis cases with different psychiatric presentations are reported and literature relevant to syphilis are reviewed

Phenotypic and Genetic Characteristics of Lipodystrophy: Pathophysiology, Metabolic Abnormalities, and Comorbidities

Purpose of reviewThis article focuses on recent progress in understanding the genetics of lipodystrophy syndromes, the pathophysiology of severe metabolic abnormalities caused by these syndromes, and causes of severe morbidity and a possible signal of increased mortality associated with lipodystrophy. An updated classification scheme is also presented.Recent findingsLipodystrophy encompasses a group of heterogeneous rare diseases characterized by generalized or partial lack of adipose tissue and associated metabolic abnormalities including altered lipid metabolism and insulin resistance. Recent advances in the field have led to the discovery of new genes associated with lipodystrophy and have also improved our understanding of adipose biology, including differentiation, lipid droplet assembly, and metabolism. Several registries have documented the natural history of the disease and the serious comorbidities that patients with lipodystrophy face. There is also evolving evidence for increased mortality rates associated with lipodystrophy.SummaryLipodystrophy syndromes represent a challenging cluster of diseases that lead to severe insulin resistance, a myriad of metabolic abnormalities, and serious morbidity. The understanding of these syndromes is evolving in parallel with the identification of novel disease-causing mechanisms