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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.

Lipedema is a chronic and progressive disease that may compromise lymphatic function. Although suction-assisted lipectomy (SAL) is considered a safe treatment for lipedema patients, the lymphatic repercussions of this surgical procedure are not fully understood. There is not enough evidence to support the role of SAL in lymphatic function treatment in lipedema. Here, we report a case of lymphatic drainage improvement after lipedema treatment with SAL. Tumescent SAL was performed in the deep subcutaneous layer, preserving the superficial and muscular lymphatic vessels. Pre- and postsurgical lymphoscintigraphy was equally documented under the Genoa protocol. A 34-year-old female patient presented with painful enlargement of the arms and lower limbs caused by lipedema. The patient had undergone conservative treatment with mild improvement in pain and heaviness. Lymphoscintigraphy showed slowed radiotracer progression on the left lower limb, collateral and tortuous lymphatic vessels on the right lower limb, and exuberant radiopharmaceutical concentration on the inguinal chain. Nine months after SAL was performed, the patient underwent another lymphoscintigraphy, which exhibited normalized radiopharmaceutical progression time and normal and symmetrical lymphatic vessel patterns. Collateral lymphatic paths and tortuosity vessels were no longer identified. Furthermore, the patient reported significant improvement in pain and the limb's appearance. Tumescent SAL is not only efficient and safe in treating lipedema, but may also be responsible for improvement in lymphatic drainage in lipedema patients. Additional prospective studies are fundamental to reinforce the current evidence and possibly yield predicting information about the tumescent liposuction eligibility in the improvement of lymphatic drainage.

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.

Introduction: Lipedema is a bilateral enlargement of the legs due to abnormal depositions of subcutaneous fat. Recent studies using lymphoscintigraphy documented that lipedema associates with lymphatic alterations. It is still not known, whether non-lipedema obesity also leads to similar lymphoscintigraphic changes within lower legs. Clinically, both, lipedema and obesity may progress to secondary lymphedema. The aim of the study was to evaluate lymphoscintigraphy of lower limbs in women with lipedema in comparison to overweight/obese women. Methods: 51 women (in the mean age of 43.3 ± 13.56) with the diagnosis of lipedema and 31 women (in the mean age of 44.7 ± 13.48) with overweight/obesity were enrolled into the study. Women in both study groups had no clinical signs of lymphedema. The groups were matched by mean volume of their legs, calculated using the formula for a truncated cone. Lymphoscintigraphy was evaluated in every women qualitatively. Body composition parameters were assessed using bioelectric impedance analysis (BIA). Results: Lymphoscintigraphic alterations within lower extremities were similar in both, lipedema and overweight/obese groups and were present in majority of women in both study groups. The most common lymphoscintigraphic alteration in both groups were additional lymphatic vessels (in the lipedema group observed in 76.5% of patients and in the overweight/obesity group – in 93.5%). Visualization of popliteal lymph nodes and dermal backflow were observed respectively in 33% and in 5.9% in the group with lipedema and in 45.2% and in 9.7% in the overweight/obesity group. There were significant relationships between severity of lymphoscintigraphic alterations and weight, lean body mass (LBM), total body water (TBW), volume of both legs and thigh circumference in the lipedema group. Such relationships were absent in the overweight/obesity group. Discussion: Our study indicates that lymphatic alterations are present before development to clinically visible secondary lymphedema in both conditions, lipedema and overweight/obesity. In majority of women from both study groups they indicate rather an overload of the lymphatic system than insufficiency. Lymphoscintigraphic alterations are similar in both groups, therefore, lymphoscintigraphy is not a diagnostic tool that might distinguish lipedema from overweight/obesity.

Lipoedema is an adipose tissue disorder almost exclusively affecting women. Evidence shows lipoedema is both poorly recognised and misdiagnosed which results in many women struggling to get a diagnosis and to gain access to specialist NHS services. This article aims to raise awareness of lipoedema and highlight the main role that community and primary care nurses can play in identifying this long-term condition earlier. It provides detail on the condition to help signpost, refer for diagnosis and initiate conservative management for those individuals with this challenging condition.