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BACKGROUND: Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema. OBJECTIVE: Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema. METHODS: Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks. RESULTS: Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity. CONCLUSION: Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.

This study aimed to assess the potential benefits of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to overweight or women with obesity. The study included 113 female participants, 56 with lipedema and 57 with overweight/obesity (BMI >25 kg/m2) without lipedema. All subjects were prescribed a low-carbohydrate, high-fat (LCHF) diet with anti-inflammatory properties to adhere to for a duration of 7 months. Measurements of anthropometry, body weight, composition, and pain (VAS) were conducted at the study’s commencement and conclusion. 52 participants completed the study. Both groups experienced a similar weight reduction, amounting to 12.9% compared to the baseline (−10.8 kg vs. −11.9 kg; p = 0.14, for lipedema and women with overweight/obesity, respectively). The most reduction was in body fat mass. Improvements in various parameters were observed, except for ankle circumferences, which decreased more in the lipedema group. Lipedema participants showed significantly reduced pain levels following the LCHF diet (4.6 ± 2.6 vs 3.0 ± 2.3; ). The LCHF diet holds promise for weight loss, body fat reduction, leg volume management, and pain alleviation in women with lipedema. These findings provide valuable insights into potential therapeutic strategies for lipedema management.

Lipedema is a chronic medical condition characterized by a symmetric buildup of adipose tissue (fat) in the legs and arms. A common but under-recognized disorder, Lipedema may cause pain, swelling, easy bruising, and impaired mobility. During the past decade, Lipedema, which occurs almost exclusively in women, has been demonstrated to be a disease that is distinct from obesity, lymphedema, cellulite, and other adipose conditions. The Lipedema Research Roadmap identifies recommendations to strengthen and grow Lipedema research. It presents a forward-looking summary of gaps in knowledge and opportunities for research and development, sourced from “Lipedema: A Current Understanding of Its Pathology and Natural History” (Lipedema Foundation; preprint, forthcoming), as well as input from authors and advisors. Recommendations are organized into six chapters covering key objectives: fostering the research environment, developing reporting standards and best practices, improving diagnosis, broadening understanding of the biology of the disease, identifying potential treatments, and enhancing epidemiology. The Research Roadmap development process incorporated input from more than 60 stakeholders, including researchers, clinicians, and patients. 24 external reviewers provided more than 1,300 comments and recommended edits.

BACKGROUND: National survey data exploring the patient experience with lipedema are lacking. METHODS: We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. RESULTS: A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m2. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; p < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; p < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; p < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; p < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; p < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; p < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; p < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; p < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). CONCLUSION: In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74—a common receptor for both cytokines—was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.

BACKGROUND: Lipedema, also known as lipohyperplasia dolorosa (LiDo), is a painful condition affecting women, causing a disproportionate accumulation of subcutaneous adipose tissue in the extremities. It carries a lower risk of diabetes and cardio-metabolic dysfunctions compared to obesity, but coincident obesity can complicate diagnosis and treatment. PATIENTS AND METHODS: This retrospective study included 607 female LiDo patients, ≥ 18 years, stage 1-3, from Germany, the UK, and Spain. Data were collected as part of the standard initial assessment for LiDo patients. RESULTS: Based on waist-to-height-ratio (WHtR), 15.2% of patients were underweight, 45.5% normal weight, 22.1% overweight and 17.3% obese. There was a significant association between WHtR category and age group. Body mass index (BMI) is often overestimated, leading to misdiagnosis of obesity. CONCLUSIONS: The use of BMI also affects the recent decision of the German Federal Joint Committee on the reimbursement of liposuction costs by health insurance funds. Patients with BMI of more than 40 kg/m2 are excluded from cost coverage, and those with BMI between 35 kg/m2 and 40 kg/m2 must first receive conservative obesity therapy. In conclusion, the sole use of BMI in lipedema is unreliable and, in contrast to WHtR, leads to inaccurate diagnoses overestimating overweight and obesity.

Lipoedema is an adipose tissue disorder that is still not fully understood. The primary purpose of this study is to explore the state of knowledge and understanding of lipoedema among Polish women. The secondary aim is to investigate the possible association between knowledge and factors such as BMI, self-reported symptoms, and age.

In recent years, the use of the ketogenic diet as a proper nutritional treatment for lipedema has been hypothesized in the literature. This is the first clinical study evaluating the ketogenic diet and carboxytherapy in lipedema patients. In the present study, it was decided to use a modified Mediterranean ketogenic diet (MMKD) in combination with carboxytherapy. Since lipedema is characterized by microangiopathy, local hypoxia, and increased subcutaneous adipose tissue (SAT) deposition, carboxytherapy could improve painful symptoms and skin tone. A total of 22 subjects were included in the data analysis, divided into three groups; 8 patients underwent MMKD combined with carboxytherapy sessions (KDCB group), 8 underwent MMKD nutritional treatment alone (KD group), and 6 patients underwent only carboxytherapy sessions (CB group), for a total of 10 weeks of treatment for all three groups. It was observed that the ketogenic diet effectively induced weight and fat mass loss, including in the limbs, areas considered unresponsive to diet therapy in lipedema patients. However, the best results were obtained from the combination of the ketogenic diet and carboxytherapy, which showed improvements in both body composition and skin texture and a reduction in pain, along with an improvement in sleep quality. It would be helpful to conduct a clinical trial on a larger scale and over a more extended period to observe the results in the long term as well.

Background: The presence of edema in patients with lipedema has been investigated in many studies. However, no study has been found that examines the amount of intracellular (ICF) and extracellular fluid (ECF) in these patients together. The aim of this study is to examine the amount of ICF and ECF in patients with stage 2 lipedema. Methods and Results: Twenty-four patients diagnosed with stage 2 lipedema were included in the study. Bioimpedance spectroscopy was applied to measure extracellular and intracellular water levels. The mean age of the participants was 44.58 ± 2.95 years. The mean body mass index (BMI) of the participants was 33.9 ± 1.84 kg/m2. It was observed that the amount of ECF in the patients was above the normal values (p < 0.001), whereas the amount of ICF was within the normal range (p = 0.801). In addition, it was observed that there was a moderate relationship between BMI and the amount of ECF. Conclusion: Although the amount of ICF is within the normal range in patients with lipedema, an increase in ECF is observed. The reason why edema is not observed in these patients despite the increase in ECF may be the increase in glycosaminoglycan and proteoglycan synthesis. In addition, the attention of these patients to weight control may contribute to slowing the course of the disease by preventing the increase in the amount of ECF. For a better diagnosis of lipedema, it is considered important to evaluate the amount of ECF in addition to routine evaluations.

IntroductionLipedema 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.MethodsSAT 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.ResultsLipedema 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.ConclusionsIn 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.

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.

Introduction Lower limb lipoedema is a chronic condition of the adipose connective tissue of the skin that affects women. Its frequency is not well known, hence the main objective of this study. Method Retrospective analysis of the records of phlebology consultations in private practice in a single center from April 2020 to April 2021. Inclusion criteria were: women aged 18 to 80 years, presenting with symptoms attributable to veins and the presence of at least one dilated reticular vein. Results The files of 464 patients were analyzed. 7.7% had lipoedema, 3.7% lymphedema, 3% stage 3 obesity. The 36 patients with lipoedema were 54.7±16 years old (mean, Standard Deviation), with a Body Mass Index of 31.3±5.5. Leg pain was the major symptom (32/36) and no patient had a positive pitting test. Conclusion Lipoedema is a frequent condition in phlebology consultations.

The aim of this study was to evaluate alterations in blood parameters after a low-carbohydrate high-fat (LCHF) diet in women with lipedema in comparison to overweight or obese women. A total of 115 women were classified into two groups: the lipedema group and the overweight/obesity group. Both study groups followed the caloric-restricted LCHF diet for 7 months. A total of 48 women completed the study. A reduction in body weight was observed in both study groups. A significant decrease in triglycerides and an increase in HDL-C concentrations were observed in both study groups. Despite the increase in the concentration of LDL-C observed in the lipedema group, changes in LDL-C differed between individual patients. Improvements in liver parameters, glucose tolerance, and a decrease in fasting insulin levels were observed, although they were less pronounced in the lipedema group than in the overweight/obesity group. Kidney and thyroid functions were similar before and after the LCHF diet in both groups. The LCHF diet may be a valuable nutritional strategy for lipedema and overweight/obese women, with a beneficial effect on weight, glucose profile, liver function, the concentration of triglycerides, and HDL-C and with no effect on kidney and thyroid function.

Background Lipedema is a loose connective tissue disease characterized by a disproportionate accumulation of adipose tissue in the limbs of women. Despite its incidence of 10-20%, lipedema is often underdiagnosed and misdiagnosed. Objectives This review aims to outline current available evidence regarding this enigmatic syndrome and gives a synopsis on the subjects that are still unknown. Materials and Methods PubMed and Embase searches were conducted to identify relevant articles on lipedema pathophysiology, clinical presentation, diagnosis and treatment. Results Lipedema can be considered a disease of the adipocytes or a circulatory disorder of the lymphatics. The relationship between lymphatics and adipose tissue remains controversial. The clinical distinction between lipedema, lymphedema, phlebolymphedema and lipolymphedema can be difficult. Diagnoses often coexist, further complicating the diagnosis of lipedema, which is currently made on clinical grounds alone. The value of diagnostic imaging studies is unclear. Liposuction appears to be an effective treatment and significantly improves symptoms. Conclusion Diagnosing lipedema remains a challenge due to its heterogeneous presentation, co-existing diseases, and the lack of objective diagnostic imaging. Further directions for research include the effect of excess skin resection surgery on lymphatic drainage.

BACKGROUND: Lipedema is a common chronic fat distribution disorder often aligned with pain and reduced quality of life affecting 6-10% of the female population. Although lipedema has acquired more scientific attention in the last decade, validated diagnosis and treatment still remain challenging for specialists. PATIENTS AND METHODS: In this article we evaluate the effect of liposuction on appearance, pain and coexisting diseases of 860 patients with lipedema. Comparison among stages of lipedema pre- and post-liposuction was performed by using t-Tests for independent samples and Kruskal-Wallis-Tests. RESULTS: Our study demonstrates the positive effect on pain reduction in patients with lipedema after liposuction (NRS 2.24) compared with pre-liposuction pain perception (NRS 6.99) and pain perception of patients with conservative treatment (NRS 6.26). Significant differences were shown in the perception between the stages of lipedema and in the reduction of pain perception by liposuction. Furthermore we examined co-diseases in patients with lipedema, primarily menstruation complaints (43%), sleeplessness (36%) and migraine (35%). CONCLUSIONS: A progress of lipedema disease leads not only to a change of appearance and proportion but also to a progressive increase of pain. Liposuction shows a significant effect on pain reduction -independent of the patients' stage of lipedema.

PURPOSE: Lipedema is a painful subcutaneous adipose tissue (SAT) disease involving disproportionate SAT accumulation in the lower extremities that is frequently misdiagnosed as obesity. We developed a semiautomatic segmentation pipeline to quantify the unique lower-extremity SAT quantity in lipedema from multislice chemical-shift-encoded (CSE) magnetic resonance imaging (MRI). APPROACH: Patients with lipedema (n=15) and controls (n=13) matched for age and body mass index (BMI) underwent CSE-MRI acquired from the thighs to ankles. Images were segmented to partition SAT and skeletal muscle with a semiautomated algorithm incorporating classical image processing techniques (thresholding, active contours, Boolean operations, and morphological operations). The Dice similarity coefficient (DSC) was computed for SAT and muscle automated versus ground truth segmentations in the calf and thigh. SAT and muscle volumes and the SAT-to-muscle volume ratio were calculated across slices for decades containing 10% of total slices per participant. The effect size was calculated, and Mann-Whitney U test applied to compare metrics in each decade between groups (significance: two-sided P<0.05). RESULTS: Mean DSC for SAT segmentations was 0.96 in the calf and 0.98 in the thigh, and for muscle was 0.97 in the calf and 0.97 in the thigh. In all decades, mean SAT volume was significantly elevated in participants with versus without lipedema (P<0.01), whereas muscle volume did not differ. Mean SAT-to-muscle volume ratio was significantly elevated (P<0.001) in all decades, where the greatest effect size for distinguishing lipedema was in the seventh decade approximately midthigh (r=0.76). CONCLUSIONS: The semiautomated segmentation of lower-extremity SAT and muscle from CSE-MRI could enable fast multislice analysis of SAT deposition throughout the legs relevant to distinguishing patients with lipedema from females with similar BMI but without SAT disease.

Lipohyperplasia dolorosa (LiDo), also known as lipedema, is a painful subcutaneous adipose tissue disorder. While the characteristic bilateral accumulation of adipocytes in extremities sparing hands and feet is investigated, an objective characterization of pain and the sensory system of LiDo patients is missing. Accordingly, progress to overcome the unsatisfying response to pain-therapeutics of patients of this widespread, lifelong, and severe disease is missing. We characterized the sensory detection profile of painful and non-painful stimuli in 20 non-obese LiDo patients and 20 waist-to-height-ratio matched controls using the clinically approved QST-protocol of the German Research Association on Neuropathic Pain (DFNS e.V.). Further, pain-reports and participants’-psychometry was assessed using the German Pain Questionnaire. LiDo patients showed no overt psychometric abnormalities. LiDo pain appeared as somatic rather than neuropathic or psychosomatic aversive. All QST measurements were normal with the selective exception of two: The pressure pain threshold (PPT) was strongly reduced and the vibration detection threshold (VDT) was strongly increased selectively at the affected thigh. In contrast, sensory profiles at the dorsum of the hand were normal. ROC-analysis of the combination of PPT and VDT of thigh versus hand shows high sensitivity and specificity, categorizing correctly 96.5% of the measured participants as LiDo patients or healthy controls, respectively. Thus, we propose to assess both, PPT and VDT, at the painful thigh and the pain-free hand as basis to develop a combined PVTH-score for differential diagnosis as a fast and convenient bedside test for the identification of non-obese LiDo patients.

In blog posts and other documents, the Lipedema Foundation sometimes presents data on growth in a number of publications in Lipedema research. For example, a statistic we often like to cite is that 50% of primary data papers on Lipedema have been published in the past 5 years. This information can b

Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses.