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Cureus Jul 2023Objective The aim of this study is to assess the prevalence of HLA-DQ2 and HLA-DQ8 in women diagnosed with lipedema. Methods Leukocyte histocompatibility antigen (HLA)...
Objective The aim of this study is to assess the prevalence of HLA-DQ2 and HLA-DQ8 in women diagnosed with lipedema. Methods Leukocyte histocompatibility antigen (HLA) tests of 95 women diagnosed with lipedema were analyzed using non-probabilistic sampling for convenience. The prevalence of HLA-DQ2 and HLA-DQ8 was compared to the general population. Results The prevalence of HLA-DQ2+ was 47.4%, that of HLA-DQ8+ was 22.2%, the presence of any celiac disease associated HLA (HLA-DQ2+ or HLA-DQ8+) was 61.1%, both HLA (HLA-DQ2+ and HLA-DQ8+) was 7.4%, and the absence of celiac disease associated HLA was 39%. Compared to the general population, there was a significantly higher prevalence of HLA-DQ2, HLA-DQ8, any HLA, and both HLAs in lipedema patients. The mean weight of patients with HLA-DQ2+ was significantly lower than the overall study population, and their mean BMI significantly differed from the overall mean BMI. Conclusion Lipedema patients seeking medical assistance have a higher prevalence of HLA-DQ2 and HLA-DQ8. Considering the role of gluten in inflammation, further research is needed to establish if this association supports the benefit of gluten withdrawal from the diet in managing lipedema symptoms.
PubMed: 37431427
DOI: 10.7759/cureus.41594 -
Cureus Feb 2023Introduction The current study aimed to investigate the overlap between symptoms of lipedema and attention-deficit/hyperactivity disorder (ADHD). Lipedema is a condition...
Introduction The current study aimed to investigate the overlap between symptoms of lipedema and attention-deficit/hyperactivity disorder (ADHD). Lipedema is a condition that causes abnormal fat accumulation and inflammation in the legs and buttocks, often accompanied by edema and pain. ADHD is a common condition characterized by difficulty paying attention and controlling behavior, affecting the social, academic, and occupational quality of life. The study's primary objective was to assess the prevalence of ADHD symptoms in a population of women with lipedema symptoms and compare the clinical characteristics. Method The study used a lipedema screening questionnaire and the Adult Self-Report Scale (ASRS-18) to assess the prevalence of ADHD in a sample of 354 female volunteers with or without a prior lipedema diagnosis. Results Of the lipedema group, 100 (77%) were ASRS positive, and 30 (23%) were ASRS negative. In the group without lipedema, 121 (54%) were ASRS positive, and 103 (46%) were ASRS negative, with a relative risk of 1.424 (p<0.0001). Conclusion Our results demonstrate a positive correlation between lipedema and ADHD and suggest that targeted strategies to improve clinic attendance for individuals with ADHD may improve lipedema treatment outcomes. Patients with lipedema symptoms are more likely to have ADHD symptoms.
PubMed: 36874317
DOI: 10.7759/cureus.35570 -
Jornal Vascular Brasileiro 2022Lipedema is characterized as an abnormal deposition of fat in the buttocks and legs bilaterally that may be accompanied by swelling, pain, and tenderness. It is still...
BACKGROUND
Lipedema is characterized as an abnormal deposition of fat in the buttocks and legs bilaterally that may be accompanied by swelling, pain, and tenderness. It is still often confused with more frequent conditions such as obesity and lymphedema. The estimated prevalence in Europe varies between 0.06% and 39%.
OBJECTIVES
To evaluate the prevalence of lipedema and identify health factors related to it in the Brazilian population.
METHODS
Administration of a previously validated online screening questionnaire to a representative sample of the general population. The questionnaire was distributed and administered to anonymous volunteers representing the general Brazilian population using software designed for population analyses.
RESULTS
253 women answered the questionnaire, 12.3 ± 4% (Confidence Interval [CI] 95%) of whom presented symptoms compatible with a high probability of being diagnosed with lipedema. Furthermore, anxiety, depression, hypertension, and anemia were also correlated with a high probability of the diagnosis.
CONCLUSIONS
The estimated prevalence of lipedema in the population of Brazilian women is 12.3%.
PubMed: 35677743
DOI: 10.1590/1677-5449.202101981 -
Frontiers in Immunology 2023Lipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas....
INTRODUCTION
Lipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far.
METHODS
SAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies.
RESULTS
Lipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype.
CONCLUSIONS
In summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.
Topics: Humans; Lipedema; Subcutaneous Fat; Adipocytes; Inflammation; Fibrosis; Hypertrophy
PubMed: 37575263
DOI: 10.3389/fimmu.2023.1223264 -
Women's Health Reports (New Rochelle,... 2020Fluid in lymphedema tissue appears histologically as spaces around vessels and between dermal skin fibers. Lipedema is a painful disease of excess loose connective...
Fluid in lymphedema tissue appears histologically as spaces around vessels and between dermal skin fibers. Lipedema is a painful disease of excess loose connective tissue (fat) in limbs, almost exclusively of women, that worsens by stage, increasing lymphedema risk. Many women with lipedema have hypermobile joints suggesting a connective tissue disorder that may affect vessel structure and compliance of tissue resulting in excess fluid entering the interstitial space. It is unclear if excess fluid is present in lipedema tissue. The purpose of this study is to determine if fluid accumulates around vessels and between skin fibers in the thigh tissue of women with lipedema. Skin biopsies from the thigh and abdomen from 30 controls and 80 women with lipedema were evaluated for dermal spaces and abnormal vessel phenotype (AVP): (1) rounded endothelial cells; (2) perivascular spaces; and (3) perivascular immune cell infiltrate. Women matched for body mass index (BMI) and age were considered controls if they did not have lipedema on clinical examination. Data were analyzed by analysis of variance (ANOVA) or unpaired -tests using GraphPad Prism Software 7. < 0.05 was considered significant. Lipedema tissue mass increases beginning with Stage 1 up to Stage 3, with lipedema fat accumulating more on the limbs than the abdomen. AVP was higher in lipedema thigh ( = 0.003) but not abdomen skin compared with controls. AVP was higher in thigh skin of women with Stage 1 ( = 0.001) and Stage 2 ( = 0.03) but not Stage 3 lipedema versus controls. AVP also was greater in the thigh skin of women with lipedema without obesity versus lipedema with obesity ( < 0.0001). Dermal space was increased in lipedema thigh ( = 0.0003) but not abdomen versus controls. Dermal spaces were also increased in women with lipedema Stage 3 ( < 0.0001) and Stage 2 ( = 0.0007) compared with controls. Excess interstitial fluid in lipedema tissue may originate from dysfunctional blood vessels (microangiopathy). Increased compliance of connective tissue in higher stages of lipedema may allow fluid to disperse into the interstitial space, including between skin dermal fibers. Lipedema may be an early form of lymphedema. ClinicalTrials.gov: NCT02838277.
PubMed: 33786515
DOI: 10.1089/whr.2020.0086 -
European Review For Medical and... Jan 2024The Editor in Chief and the Publisher are issuing an expression of concern to alert readers to the fact that the Special Issue titled "Omics sciences in the...
The Editor in Chief and the Publisher are issuing an expression of concern to alert readers to the fact that the Special Issue titled "Omics sciences in the personalization of diagnosis and therapy" and, in particular, the following articles: · J. Kaftalli, K. Donato, G. Bonetti, K. Dhuli, A. Macchia, P.E. Maltese, K. Louise Herbst, S. Michelini, P. Chiurazzi, M. Hill, S. Michelini, S. Michelini, G. Marceddu, A. Bernini, M. Bertelli. Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as causative factors. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 127-136. DOI: 10.26355/eurrev_202312_34697-PMID: 38112953. · M.C. Medori, K. Donato, L. Stuppia, T. Beccari, M. Dundar, R.S. Marks, S. Michelini, E. Borghetti, C. Zuccato, L. Seppilli, H. Elsangak, G. Sozanski, D. Malacarne, M. Bertelli. Achievement of sustainable development goals through the Mediterranean diet. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 89-99. DOI: 10.26355/eurrev_202312_34693-PMID: 38112950. · K. Donato, M.C. Medori, A. Macchia, S. Cecchin, M.R. Ceccarini, T. Beccari, V. Gatta, L. Stuppia, V. Benfatti, L. Dalla Ragione, P. Chiurazzi C. Micheletti, K. Dhuli, G. Madeo, G. Bonetti, G. Marceddu, M. Bertelli. Genetic variants identified in novel candidate genes for anorexia nervosa and analysis of molecular pathways for diagnostic applications. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 77-88. DOI: 10.26355/eurrev_202312_34692-PMID: 38112957. · K. Donato, K. Dhuli, A. Macchia, M.C. Medori, C. Micheletti, G. Bonetti, M.R. Ceccarini, T. Beccari, P. Chiurazzi, S. Cristoni, V. Benfatti, L. Dalla Ragione, M. Bertelli. Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 64-76. DOI: 10.26355/eurrev_202312_34691-PMID: 38112949. · M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli. Autoantibodies detection in patients affected by autoimmune retinopathies. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63. DOI: 10.26355/eurrev_202312_34690-PMID: 38112948. · E. Kalluçi, E. Noka, K. Bani, X. Dhamo, I. Alimehmeti, K. Dhuli, G. Madeo, C. Micheletti, G. Bonetti, C. Zuccato, E. Borghetti, G. Marceddu, M. Bertelli. Correlation between COVID-19 and air pollution: the effects of PM2.5 and PM10 on COVID-19 outcomes. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 39-47. DOI: 10.26355/eurrev_202312_34688-PMID: 38112947. · K. Dhuli, C. Micheletti, M.C. Medori, G. Madeo, G. Bonetti, K. Donato, F. Gaffuri, G.M. Tartaglia, S. Michelini, A. Fiorentino, D. Cesarz, S.T. Connelly, N. Capodicasa, M. Bertelli. The potential preventive role of a dietary supplement containing hydroxytyrosol in COVID-19: a multi-center study. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 33-38. DOI: 10.26355/eurrev_202312_34687-PMID: 38112946. · K. Dhuli, M.C. Medori, C. Micheletti, K. Donato, F. Fioretti, A. Calzoni, A. Praderio, M.G. De Angelis, G. Arabia, S. Cristoni, S. Nodari, M. Bertelli. Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 13-19. DOI: 10.26355/eurrev_202312_34685-PMID: 38112944. are being reviewed again after publication by an independent Editor and a new group of reviewers due to concerns raised by readers on PubPeer regarding an undisclosed authors' conflict of interest and methodological issues of some articles. Further updates will be provided once the investigation is completed. The authors have been notified about this expression of concern.
PubMed: 38305629
DOI: 10.26355/eurrev_202401_35160 -
Obesity (Silver Spring, Md.) Jul 2022Lipedema is an inflammatory subcutaneous adipose tissue disease that develops in women and may progress to lipolymphedema, a condition similar to lymphedema, in which...
OBJECTIVE
Lipedema is an inflammatory subcutaneous adipose tissue disease that develops in women and may progress to lipolymphedema, a condition similar to lymphedema, in which lymphatic dysfunction results in irresolvable edema. Because it has been shown that dilated lymphatic vessels, impaired pumping, and dermal backflow are associated with presymptomatic, cancer-acquired lymphedema, this study sought to understand whether these abnormal lymphatic characteristics also characterize early stages of lipedema prior to lipolymphedema development.
METHODS
In a pilot study of 20 individuals with Stage I or II lipedema who had not progressed to lipolymphedema, lymphatic vessel anatomy and function in upper and lower extremities were assessed by near-infrared fluorescence lymphatic imaging and compared with that of a control population of similar age and BMI.
RESULTS
These studies showed that, although lower extremity lymphatic vessels were dilated and showed intravascular pooling, the propulsion rates significantly exceeded those of control individuals. Upper extremity lymphatics of individuals with lipedema were unremarkable. In contrast to individuals with lymphedema, individuals with Stage I and II lipedema did not exhibit dermal backflow.
CONCLUSIONS
These results suggest that, despite the confusion in the diagnoses between lymphedema and lipedema, their etiologies differ, with lipedema associated with lymphatic vessel dilation but not lymphatic dysfunction.
Topics: Edema; Female; Humans; Lipedema; Lymphatic Vessels; Lymphedema; Pilot Projects
PubMed: 35707862
DOI: 10.1002/oby.23458 -
European Review For Medical and... Jul 2019The aim of this qualitative review is to provide an update on the current understanding of the genetic determinants of lipedema and to develop a genetic test to... (Review)
Review
OBJECTIVE
The aim of this qualitative review is to provide an update on the current understanding of the genetic determinants of lipedema and to develop a genetic test to differentiate lipedema from other diagnoses.
MATERIALS AND METHODS
An electronic search was conducted in MEDLINE, PubMed, and Scopus for articles published in English up to March 2019. Lipedema and similar disorders included in the differential diagnosis of lipedema were searched in the clinical synopsis section of OMIM, in GeneCards, Orphanet, and MalaCards.
RESULTS
The search identified several genetic factors related to the onset of lipedema and highlighted the utility of developing genetic diagnostic testing to help differentiate lipedema from other diagnoses.
CONCLUSIONS
No genetic tests or guidelines for molecular diagnosis of lipedema are currently available, despite the fact that genetic testing is fundamental for the differential diagnosis of lipedema against Mendelian genetic obesity, primary lymphedema, and lipodystrophies.
Topics: Aldehyde Dehydrogenase; Databases, Factual; Histone-Lysine N-Methyltransferase; Humans; Lipedema; Lipodystrophy, Familial Partial; Multidrug Resistance-Associated Proteins; Perilipin-1; Severity of Illness Index; Trans-Activators
PubMed: 31298310
DOI: 10.26355/eurrev_201907_18292 -
European Review For Medical and... Dec 2023Lipedema is an autosomal dominant genetic disease that mainly affects women. It is characterized by excess deposition of subcutaneous adipose tissue, pain, and anxiety....
OBJECTIVE
Lipedema is an autosomal dominant genetic disease that mainly affects women. It is characterized by excess deposition of subcutaneous adipose tissue, pain, and anxiety. The genetic and environmental etiology of lipedema is still largely unknown. Although considered a rare disease, this pathology has been suggested to be underdiagnosed or misdiagnosed as obesity or lymphedema. Steroid hormones seem to be involved in the pathogenesis of lipedema. Indeed, aldo-keto reductase family 1 member C1 (AKR1C1), a gene coding for a protein involved in steroid hormones metabolism, was the first proposed to be correlated with lipedema.
PATIENTS AND METHODS
In this study, we employed a molecular dynamics approach to assess the pathogenicity of AKR1C1 genetic variants found in patients with lipedema. Moreover, we combined information theory and structural bioinformatics to identify AKR1C1 polymorphisms from the gnomAD database that could predispose to the development of lipedema.
RESULTS
Three genetic variants in AKR1C1 found in patients with lipedema were disruptive to the protein's function. Furthermore, eight AKR1C1 variants found in the general population could predispose to the development of lipedema.
CONCLUSIONS
The results of this study provide evidence that AKR1C1 may be a key gene in lipedema pathogenesis, and that common polymorphisms could predispose to lipedema development.
Topics: Female; Humans; Hormones; Lipedema; Lymphedema; Steroids; Subcutaneous Fat
PubMed: 38112954
DOI: 10.26355/eurrev_202312_34698 -
La Clinica Terapeutica 2023Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic... (Review)
Review
BACKGROUND
Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic investigations have uncovered potential contributors to its pathogenesis, including somatic mutations, which are nonheritable genetic alterations that can play a pivotal role in the development of this disease.
AIM
This review aims to elucidate the role of somatic mutations in the etiology of lipedema by examining their implications in adipose tissue biology, inflammation, and metabolic dysfunction.
RESULTS
Studies focusing on leukocyte clones, genetic alterations like TET2 and DNMT3A, and the intricate interplay between adipose tissue and other organs have shed light on the underlying mechanisms driving lipedema. From the study of the scientific literature, mutations to genes correlated to three main pathways could be involved in the somatic development of lipedema: genes related to mitochondrial activity, genes related to localized disorders of subcutaneous adipose tissue, and genes of leukocyte clones.
CONCLUSIONS
The insights gained from these diverse studies converge to highlight the complex genetic underpinnings of lipedema and offer potential avenues for therapeutic interventions targeting somatic mutations to alleviate the burden of this condition on affected individuals.
Topics: Humans; Lipedema; Quality of Life; Subcutaneous Fat; Adipose Tissue; Inflammation
PubMed: 37994772
DOI: 10.7417/CT.2023.2495