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BACKGROUND: Lipedema is a chronic inflammatory subcutaneous adipose-rich connective tissue disease affecting millions of women worldwide. Disproportionate fat accumulation on the extremities characterized by heaviness, tenderness, and swelling can affect function, mobility, and quality of life. Treatments include conservative measures and lipedema reduction surgery (LRS). Here, we report lipedema comorbidities and surgical techniques, outcomes measures, and complications after LRS. METHODS: This is a single outpatient clinic retrospective chart review case series of comorbidities and complications in 189 women with lipedema. Bioelectrical impedance analyses, knee kinematics, gait, physical examinations, Patient-Reported Outcomes Measurement Information System, and RAND Short Form-36 questionnaires collected before and after LRS were analyzed for 66 of the 189 women. Hemoglobin levels were measured by transdermal hemoglobin monitor (Masimo noninvasive hemoglobin monitoring; Irvine, Calif.). RESULTS: Common comorbidities in 189 women were hypermobile joints (50.5%), spider/varicose veins (48.6/24.5%), arthritis (29.1%), and hypothyroidism (25.9%). The most common complication in 5.5% of these women after LRS was lightheadedness with a 2-g reduction or more in hemoglobin. After conservative measures and LRS in 66 women, significant improvements (P ≤ 0.0009) were found for: (1) knee flexion (10 degrees); (2) gait; (3) Patient-Reported Outcomes Measurement Information System T-score (16%); (4) mobility questions: gait velocity, rising from a chair, stair ascent; (5) RAND Short Form-36 scores: physical functioning, energy/fatigue, emotional well-being, social function, general health; (6) and Bioelectrical impedance analyses total and segmental body fat mass. CONCLUSION: LRS provided significant improvements to women with lipedema using direct physical measurements and validated outcome measures, comparable to those seen after total knee replacement.

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.

Background: Lipedema is a chronic and progressive disease. Many complications can occur if the disease is not treated. The most important of these complications is lipedema with secondary lymphedema. There are very few publications about lipedema with secondary lymphedema. The aim of this study is to investigate the effect of physical therapy on lower extremity circumference and volume in patients suffering from lipedema with secondary lymphedema. Methods and Results: All patients received pneumatic compression and complex decongestive therapy (CDT). Perometer measurement was made at five distinct points. Fifteen patients were included in the study. It was seen that significant reduction was found in the circumference of three of the five points of measurements performed in the left leg, whereas significant reduction was found in the circumference of four of the five points of measurements performed in the right leg. Also, there was a decrease in the extremity volume in both legs. Conclusion: Combined application of CDT and pneumatic compression in patients suffering from lipedema with secondary lymphedema is an effective treatment method in reducing lower extremity volume and circumference measurement.

BACKGROUND: Diagnosing lipedema remains a challenge due to its heterogeneous presentation, co-existing diseases, and the lack of objective diagnostic imaging. OBJECTIVE: This systematic review aims to outline the currently available diagnostic imaging methods to characterize lipedema in the legs along with their diagnostic performance. METHODS: PubMed, Embase, Google Scholar, Scopus, and Web of Science were searched. The quality assessment of diagnostic accuracy studies (QUADAS) tool was used for quality assessment. RESULTS: Thirty-two studies describing a total of 1154 patients with lipedema were included for final analysis. Features for lipedema have been defined using ultrasound (increased subcutaneous adipose tissue), lymphoscintigraphy (slowing of the lymphatic flow and a frequent asymmetry between the lower extremities), computed tomography (symmetrical bilateral soft tissue enlargement without either skin thickening or subcutaneous edema), magnetic resonance imaging (increased subcutaneous adipose tissue), MR lymphangiography (enlarged lymphatic vessels up to a diameter of 2 mm), and dual-energy X-ray absorptiometry (fat mass in the legs adjusted for body mass index (BMI) ≥ 0.46 or fat mass in the legs adjusted for total fat mass ≥ 0.384). CONCLUSION: The diagnostic performance of currently available imaging modalities for assessing lipedema is limited. Prospective studies are needed to evaluate and compare the diagnostic performance of each imaging modality. Imaging techniques focusing on the pathogenesis of the disease are needed.

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.

Lipedema is a connective tissue disorder characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. This project aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). The impacts on the expression levels of multiple endothelial and angiogenic markers [CD31, von Willebrand Factor (vWF), angiopoietin 2 (ANG2), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMPs), NOTCH and its ligands] in HUVECs were investigated. The data demonstrate an increased expression of CD31 and ANG2 at both the gene and protein levels in HUVECs treated with AQL CM in 2D monolayer and 3D cultures compared to untreated cells. Furthermore, the expression of the vWF, NOTCH 4, and DELTA-4 genes decreased. In contrast, increased VEGF, MMP9, and HGF gene expression was detected in HUVECs treated with AQL CM cultured in a 2D monolayer. In addition, the results of a tube formation assay indicate that the number of formed tubes increased in lipedema-treated HUVECs cultured in a 2D monolayer. Together, the data indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.

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.

BACKGROUND: Lipedema is a chronic disease marked by symmetric enlargement of painful nodular and fibrotic adipose tissue, predominantly affecting the limbs. Since there is no specific test or biomarker for this condition, years often pass before the diagnosis of lipedema is established for the first time, thereby causing psychosocial distress, including depression, eating disorders, and social isolation. Over the last few years several advanced Doppler-based technologies have been developed to visualize slow flow blood vessels and superficial microvascular architecture undetectable by traditional color Doppler flow imaging (CDFI). OBJECTIVE: The aim of this study was to evaluate the superficial microvascular anatomy in lipedema patients compared to healthy controls and investigate the clinical significance of the Ultra Micro Angiography (UMA) technology in the diagnosis of lipedema. This new technique may contribute to reduce the diagnostic delay and, eventually, establish and guide treatment strategies toward a better therapeutic outcome in lipedema patients. METHODS: 25 patients with lipedema and ten healthy controls with no history of lipedema were included in this study. All ultrasound examinations were performed on a novel high-performance ultrasound system (Resona R9/Mindray) using CDFI and the UMA technique. RESULTS: In all of the patients, Ultra Micro Angiography achieved the excellent visualization of microvascular structures, revealing that most lipedema patients showed grade 3 (n = 13) or grade 2 (n = 8) flow. UMA was superior to CDFI for depicting the microvascular structures. CONCLUSIONS: Here we show that UMA imaging characterizes the subcutaneous microvasculature with an unprecedented accuracy. The method has the advantage of being sensitive to small, slow-flowing vessels. This allows for the assessment of the course of vessels and vascular pathologies in great detail. Thus, UMA as a non-invasive diagnostic method can improve diagnostic accuracy in lipedema.

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.

Pain, which is a central characteristic of lipedema, allows differentiation from other fat tissue diseases. The analysis of the multiple aspects of pain beyond a quantification of pain scale scores could make molecular disease and therapy mechanisms accessible. Lipedema pain is causally linked to lipedema fat. First robust data show peripheral sensory changes. Tissue weight and systemic inflammation are becoming less likely as causes for the experianced pain. Furthermore, genetics and hormonal influences need to be investigated. Lipedema pain cannot currently be treated with drugs. Physical therapy shows transient relief. Liposuction has been shown to have a long-term effect on pain. The potential of modulating the perception of pain with psychotherapeutic approaches is emerging as a potentially effective new therapeutic approach.

Lipohyperplasia dolorosa (LiDo) is a genetic, painful fat tissue distribution disorder with lymphological high-volume transport insufficiency. It often has negative effects on the psychological well-being of affected female adolescents and adults. Similar in appearance to the development of obesity, the patients experience similar negative reactions in their families, partners and friends. The development of the LiDo usually occurs in adolescence or following pregnancy and represents a considerable psychological burden in central phases of narcissistic development. These psychological impairments caused by LiDo are long-term companions and influence interpersonal relationships. Three case vignettes serve for clarification. In the first case, the LiDo seems to be "grafted" onto a neurotic conflict, which intensifies the acute and chronic pain of the person affected. In the second case, the affected person shows defense mechanisms in contact, which are evidence of a high level of stress and require considerable sensitivity by the person's social circle during interactions. In the third case, after intensively addressing various aspects of the disease, the person received medical treatment from a specialist and underwent several surgeries. The positive effects on physical and psychological well-being are stabilized by psychological support. Seen as an option, those affected can decide for or against surgical treatment. As a consequence of the treatment, the previously rejected extremities become more integrated, arms and legs fit back into the person's own physical image of the body. This positive change also extends to the intrapsychic self-image of the body.

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.

The billing of lipoedema treatment in Germany has come to be heterogeneous. This is due to the decision of the Federal Joint Committee ("Gemeinsamer Bundesausschuss", G-BA) to acknowledge lipoedema stage III as a treatment to be paid by the statutory health insurance funds ("Gesetzliche Krankenversicherung", GKV) until the completion of the trial study "LipLeg" at the end of 2024. Based on this decision, inpatient and outpatient surgical treatment of stage III lipoedema can be billed to the GKV, while the reimbursement of costs for surgical treatment of the other two stages remains a case-by-case decision of the GKV and is currently often rejected. Therefore, treatment costs are often paid by patients themselves. The question of the correct settlement of lipoedema treatment repeatedly arises in the context of legal disputes, which, in turn, repeatedly faces experts and courts with a major challenge. In the following article, the Task Force Lipoedema of the German Society for Plastic, Reconstructive and Aesthetic Surgery presents an overview of the various billing modalities and presents a proposal for the correct billing of lipoedema within the framework of the German medical fee schedule ("Gebührenordnung für Ärzte", GOÄ).

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.