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ObjectivesThis study aimed to analyze the complex components of pain in lipedema and to evaluate correlations among key pain-related parameters, including intensity, hypersensitivity, catastrophizing, central sensitization, and neuropathic pain.MethodsThis prospective study was conducted between June 2025 and September 2025. Patients aged 18 or older with a diagnosis of lipedema were included. Demographic/clinical characteristics were recorded. Pain intensity, hypersensitivity, pain catastrophizing, central sensitization, and neuropathic pain were assessed using the Numeric Rating Scale (NRS), a 0-3 verbal rating scale, the Pain Catastrophizing Scale, the Central Sensitization Inventory, and the painDETECT questionnaire, respectively.ResultsA total of 85 patients were included in the study. Patients had a median age of 44 years, a median Body Mass Index of 29.24 kg/m2, and most were classified as stage 2 lipedema (50.6%). Pain intensity was moderate, with a median NRS score of 5, while hypersensitivity levels were moderate (41.2%) to high (34.1%) in most patients. Pain catastrophizing, central sensitization, and neuropathic pain were present in 35.1%, 83.5%, and 27.1% of the patients, respectively. Pain intensity was significantly positively correlated with hypersensitivity, pain catastrophizing, central sensitization, and neuropathic pain (p < 0.05). All parameters were significantly correlated with each other (p < 0.05).ConclusionCentral sensitization may be observed in patients with lipedema and is associated with other pain parameters. The findings highlight significant interrelationships among pain intensity, hypersensitivity, pain catastrophizing, and central sensitization. Pain needs to be assessed in detail in patients with lipedema.

BACKGROUND: Postoperative fibrosis is a frequent complication following liposuction for lipedema. Serrapeptase, a proteolytic enzyme with purported anti-inflammatory and antifibrotic effects, is used empirically, but robust evidence supporting its efficacy is lacking. This study aimed to assess the clinical effectiveness of postoperative serrapeptase supplementation in reducing fibrosis following lower limb liposuction for lipedema. METHODS: This retrospective, observational cohort study included 50 female patients with a confirmed diagnosis of lipedema undergoing tumescent liposuction. Patients were allocated to either a serrapeptase group (n = 25), receiving 60,000 IU daily for 4 weeks, or a control group (n = 25) receiving standard care alone. The primary outcome was tissue stiffness measured by quantitative ultrasound elastography (QUS). Secondary outcomes included B-mode ultrasonography, patient-reported pain (VAS), and clinical assessment of induration. Evaluations were performed at baseline, 4 weeks, and 3 months. RESULTS: Baseline characteristics were comparable between groups. No statistically significant differences were observed in the primary outcome of tissue stiffness at 4 weeks (14.8 ± 3.1 kPa vs. 15.2 ± 3.0 kPa; p = 0.62) or 3 months (13.7 ± 2.9 kPa vs. 14.0 ± 3.2 kPa; p = 0.78). Similarly, no significant benefits were seen in secondary outcomes, including fibrotic changes on ultrasound, VAS pain scores, or clinical induration (p > 0.05 for all). Serrapeptase was well-tolerated with no adverse events reported. CONCLUSIONS: Oral serrapeptase supplementation did not demonstrate measurable efficacy in preventing postoperative fibrosis or improving patient-reported outcomes following liposuction for lipedema. These findings do not support its routine use in this clinical setting. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

ObjectiveTo evaluate the educational quality, reliability, and transparency of YouTube™ videos on lipoedema, and to examine associations with uploader type and engagement metrics.MethodsOn 15 May 2025 we searched YouTube™ for "lipoedema," screened the first 200 relevance-ranked items, and included videos ≥60 s with intelligible audio. Advertisements, duplicates and soundless videos were excluded. Two independent physicians in Physical Medicine and Rehabilitation (PM&R) rated eligible videos using DISCERN, the Global Quality Score (GQS), and the Journal of the American Medical Association (JAMA) benchmark criteria; disagreements were discussed and original ratings retained for agreement analyses. We recorded upload date, duration, views, likes, comments, channel subscribers, uploader category, and content domain.ResultsWe analyzed 92 YouTube™ lipoedema videos uploaded between 25 February 2015 and 8 January 2025. Uploader mix: vascular surgeons 39.1% (largest) and PM&R physicians 4.3% (smallest); the most common topic was definition + symptoms + management (26.1%). Mean DISCERN totals were 33.47 ± 9.88 and 33.42 ± 8.68 (both poor); mean GQS 2.18 ± 0.82 and 2.43 ± 0.81; only 6.6% were high quality and none scored 5/5. Views correlated strongly with likes and comments (both p < .001), moderately with duration (p < .01), and weakly with subscribers (p < .05). Inter-rater agreement was strong (r = 0.859/0.663/1.000; all p < .001).ConclusionThe overall quality and transparency of YouTube™ lipoedema videos are suboptimal despite substantial engagement. Increasing expert-authored, evidence-based content-particularly from PM&R- and co-produced patient-clinician videos may better align reliability with reach.

BACKGROUND: lipedema is a chronic, progressive adipose disorder predominantly affecting women, characterized by painful, symmetrical subcutaneous fat accumulation, and typically resistant to lifestyle interventions. The pathophysiology of advanced-stage lipedema remains poorly defined, and no validated biomarkers or targeted therapies are currently available. METHODS: in this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema. RESULTS: Genome-wide DNA methylation profiling identified over 5,000 differentially methylated CpG sites affecting genes involved in receptor tyrosine kinase signaling, phospho-metabolism, and immune pathways. Transcriptomic analysis revealed profound downregulation of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and fatty acid β-oxidation, alongside disruption of the sirtuin pathway and extracellular matrix remodeling. Integrative analysis pinpointed AKT1 as a central regulatory node: its promoter region was hypomethylated, correlating with increased gene expression and protein phosphorylation. Metabolomic profiling confirmed AKT1-linked metabolic dysregulation, including altered levels of L-arginine, NADP+, ATP, guanosine, glycerol, and glutamate, indicating impaired redox balance and energy metabolism. Trans-omic network analysis positioned AKT1 at the intersection of multiple dysregulated pathways, suggesting its key role in advanced-stage lipedema. CONCLUSIONS: the consistent enhancing of AKT pathway signaling across omic layers highlights its potential not only as a biomarker for disease stratification but also as a putative druggable target for therapeutic intervention. These findings offer new mechanistic insights into lipedema pathophysiology and provide a rationale for future personalized treatment strategies guided by AKT1-centric molecular profiling.

PURPOSE: Lipedema is a chronic disorder that affects the subcutaneous adipose tissue of the lower and upper limbs and results in painful fat accumulations. During the reproductive life span, about 11% of women are affected; however, there are a high number of suspected undiagnosed and thus untreated cases. METHODS: The aim of this systematic review was to evaluate the association between hormones and the pathophysiological mechanisms of lipedema development. Inclusion criteria were: lipedema, lipoedema, estrogen, estrogen antagonists, female sex hormones, hormones, insulin, puberty, pregnancy, menopause, subcutaneous fat tissue, and subcutaneous adipose connective tissue. RESULTS: The literature search yielded 121 hits; after deduplication, 64 records were screened. After abstract and full-text screening 15 publications were suitable for being included in the systematic review. Overall, four different pathophysiological hypotheses were postulated: (1) general hormonal imbalance, (2) changes in growth hormone balance, (3) metabolic imbalance such as changes in adipose stem cells in relation to adipokines or leptin in association with the transcription factor PPARγ, and (4) changes in estrogen metabolism as well as alterations in the function of estrogen receptors. CONCLUSION: Lipedema appears to be a multifactorial condition primarily driven by hormonal dysregulation-especially involving estrogen-alongside metabolic and possible genetic components. The findings support the reclassification of lipedema as a hormonally influenced disorder distinct from obesity, emphasizing the need for further research into diagnostic biomarkers, targeted therapies, and the role of genetic susceptibility.

BackgroundEndothermal ablation (ETA) is a well-established treatment for chronic venous insufficiency (CVI). However, its effectiveness in patients with concomitant lipedema remains poorly described. Given the distinct pathophysiological features and symptom burden of lipedema, outcomes may differ in this subgroup.MethodsWe conducted a prospective cohort study of patients with CVI alone and those with CVI plus lipedema. All patients underwent ETA, with adjunctive phlebectomies as indicated. Quality of life (QoL) was assessed using the EQ-5D-VAS and CIVIQ-20 questionnaires before surgery and at 3 months postoperatively. Demographic and clinical variables included age, body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and symptom profile. The primary outcome was the change in CIVIQ-20 score at 3 months. Secondary outcomes included changes in EQ-5D-VAS and postoperative complications (hematoma, paresthesia, superficial and deep vein thrombosis).ResultsA total of 48 patients were included (32 with CVI alone, 16 with CVI and lipedema). Preoperative QoL impairment was significantly greater in the lipedema cohort (median CIVIQ-20: 61.0 [49.5-69.5]) compared with CVI alone (46.0 [33.0-56.0], p = .001). At 3 months, both groups demonstrated significant improvement (p < .001 for within-group change). However, the magnitude of improvement was greater in CVI alone (median reduction: -13.5 [-19.5 to -5.0]) than in CVI plus lipedema (-4.0 [-7.0 to -1.5]; p = .012). Multivariable regression identified higher baseline CIVIQ-20 (β = 0.60; SE = 0.09; p < .001) and lipedema status (β = 12.44; SE = 2.43; p < .001) as independent predictors of poorer postoperative CIVIQ-20 outcomes. Paresthesia was more frequent in lipedema patients (25.0% vs 18.8% at 1 month; 12.5% vs 6.2% at 3 months).ConclusionWhile ETA significantly improves QoL in patients with CVI, those with concomitant lipedema experience smaller gains and a higher rate of postoperative paresthesia. These findings highlight the importance of setting realistic expectations and counseling lipedema patients regarding potential outcomes of venous interventions.

Lipedema is a chronic disease characterized by the symmetrical accumulation of adipose tissue in the lower body, primarily affecting women. Despite being recognized for over 85 years, the pathophysiology, diagnosis, and treatment of lipedema remain complex and not fully understood. This review consolidates current knowledge, emphasizing histological, genetic, and hormonal factors, alongside diagnostic and therapeutic approaches. Histological studies highlight changes such as adipocyte hypertrophy, increased fibrosis, and vascular alterations like angiogenesis. Genetic studies suggest a strong familial component, with multiple loci potentially influencing disease onset, yet the condition remains polygenic and influenced by environmental factors. Hormonal influences, particularly estrogen, play a significant role in disease pathogenesis. Diagnostic imaging techniques like dual-energy X-ray absorptiometry (DXA), ultrasound (US), and magnetic resonance imaging (MRI) provide valuable insights but are not definitive. Therapeutic strategies, including diet, weight loss, and Complex Decongestive Therapy, offer symptom management but are not curative, with liposuction considered for severe cases where conservative methods fail. The condition's complexity stems from genetic, hormonal, and environmental influences, necessitating further research to improve diagnostic and treatment strategies. Integrating genetic and hormonal insights into clinical practice could enhance patient outcomes and quality of life, highlighting the need for continued exploration and understanding of lipedema.

Lipedema predominantly affects women and is characterized by an abnormal distribution of adipose tissue, accompanied by pain or discomfort in affected areas. Despite growing awareness, inconsistent diagnostic criteria and treatment approaches hinder medical care and research. This multi-phase Delphi study was conducted to address the need for internationally accepted consensus on fundamental aspects of the disease. Through online surveys and an in-person discussions, experts representing 19 countries evaluated on 62 original statements regarding (1) clarity, (2) agreement, (3) recommendation for inclusion, (4) strength of evidence, and (5) whether additional evidence was needed. Ultimately, 59 statements reached consensus across eight domains encompassing the definition and management of lipedema. The findings provide a framework to guide internationally applicable recommendations for patients with lipedema that may improve outcomes globally. Limited evidence in several areas highlights the importance of further research, standardization of data reporting, and international collaboration among healthcare providers, researchers, and patient advocates to address this women's health disparity effectively.

Lipedema is a chronic, underdiagnosed adipose disorder marked by disproportionate fat accumulation, pain, and impaired mobility. Misdiagnosis as obesity or lymphedema delays care and increases morbidity. We systematically reviewed clinical features, diagnostic criteria, and management options (conservative and surgical). A comprehensive search of the PubMed database was conducted in January 2025 for English-language articles published from January 1950 to January 2023 using the keywords "lipedema" or "lipoedema." Additional references were identified via manual review of relevant systematic reviews. Two independent reviewers screened studies and graded quality using a modified Oxford scale. Of 339 articles, 61 met the inclusion criteria. Most were observational cohorts, case series, or expert consensus, with few randomized trials. Conservative therapies, including ketogenic or Rare Adipose Disorders (RAD) diets, compression therapy, and aquatic exercise, were associated with reduced pain and swelling (Grade 2A-2B). Tumescent liposuction showed the strongest evidence for sustained symptom improvement, mobility, and quality of life (Grade 1 recommendation, evidence quality 2-3). Lipedema is a distinct, progressive condition requiring early recognition and intervention. Conservative therapies may provide partial relief, but tumescent liposuction remains the most effective treatment. Standardized diagnostic criteria, validated patient-reported outcomes, and clearer guidelines are needed to harmonize care and improve long-term outcomes.

BackgroundLipedema is a chronic disorder involving abnormal accumulation of subcutaneous fat, primarily in the lower limbs. Liposuction is an effective treatment, but postoperative complications such as fluid retention and seroma formation are common. While the use of surgical drains is well established in other areas of plastic surgery, their role in lipedema liposuction remains unclear.MethodsThis prospective observational study involved 50 consecutive patients with stage II or III lipedema who underwent lower leg liposuction. A novel passive drainage technique was used, involving glove drains fashioned from sterile, powder-free nitrile gloves and inserted through existing liposuction incisions. Drain duration, postoperative swelling, and complications, particularly seroma formation, were evaluated.ResultsAll patients completed follow-up with no major complications. Glove drains remained in place for an average of 2.4 ± 0.5 days. Only 2 patients (4%) developed seromas requiring single aspiration. No infections, hematomas, or lymphatic complications were recorded. Patients reported reduced swelling and discomfort compared to historical cases without drains.ConclusionPassive glove drains appear to be a simple, safe, and effective method to manage postoperative fluid collections after lipedema liposuction of the lower legs. The technique may lower the risk of seroma formation and promote early recovery, characterized by reduced postoperative edema, improved patient comfort, and an uncomplicated short-term postoperative course. Further controlled studies are needed to validate these findings and establish standardized drainage protocols in lipedema surgery.

Review Article Background: Lipedema and advanced lymphedema are chronic disorders of adipose and lymphatic tissues that remain frequently underdiagnosed. Their coexistence poses therapeutic challenges, particularly when conservative management fails. Although international guidelines support surgical intervention in selected cases, real-world data from resourcelimited hospital settings remain scarce. Objective: To report the experience of a Moroccan tertiary university hospital in the surgical management of advanced lipedema and lymphedema and to compare clinical outcomes with current international recommendations. Methods: A retrospective descriptive case series was conducted between 2021 and 2024. Three patients underwent surgical treatment using tumescent liposuction or en bloc tissue resection with skin grafting. Postoperative outcomes were assessed clinically and through a structured quality-of-life questionnaire inspired by the SF-36, focusing on pain, mobility, and overall satisfaction. Results: All procedures were completed without intraoperative or postoperative complications. The volume of aspirated adipose tissue ranged from 2.1 to 4.0 L. One patient with advanced secondary lymphedema required surgical resection, with evacuation of 1.2 L of lymphorrhea. Postoperative satisfaction ranged from moderate to high, with reported quality-of-life scores between 5 and 8 out of 10. These findings are consistent with outcomes reported in recent international series. Conclusion: Surgical treatment of advanced lipedema and lymphedema is feasible, safe, and clinically beneficial, even in resource-limited settings. An individualized, guideline-based approach allows satisfactory functional and quality-of-life outcomes. Further prospective studies with standardized assessment tools are required.

ObjectivesLipedema is a chronic condition that predominantly affects women, leading to painful, disproportionate fat distribution in the limbs. This systematic review and meta-analysis aimed to characterize health-related quality of life (HRQoL) across multiple domains in individuals with lipedema.MethodsWe systematically reviewed studies from inception to 3 July 2025 in MEDLINE (via PubMed) and Cochrane Controlled Register of Trials (CENTRAL) that primarily assessed HRQoL in individuals with lipedema. Data were extracted from studies using HRQoL assessment scales. The methodological quality of included studies was assessed using an adapted version of the Newcastle-Ottawa Scale for cross-sectional studies. The review protocol was pre-registered with PROSPERO (CRD42024590792). A random-effects meta-analysis was conducted to compute pooled mean HRQoL scores across various domains.ResultsFourteen cross-sectional studies involving nine countries and 3851 participants were included. The meta-analysis found significant impairments in multiple HRQoL domains: physical functioning (61.19, 95% CI: 56.77-65.60), pain (51.77, 95% CI: 45.01-58.53), social functioning (63.24, 95% CI: 58.44-68.04), emotional well-being (64.19, 95% CI: 59.86-68.52), and energy/fatigue (43.50, 95% CI: 39.32-47.68).ConclusionLipedema significantly affects HRQoL, with major deficits in physical, emotional, and social functioning. These findings highlight the need for greater clinical awareness and comprehensive management strategies, including both physical and psychological interventions, to improve the quality of life for individuals with lipedema. Further research is needed to explore long-term effects and optimize treatment approaches.

INTRODUCTION: Lipedema causes abnormal fat accumulation in the limbs, leading to pain, functional impairment, and body image disturbance. Nowadays, various liposuction techniques are available. The wet technique is increasingly being considered as the gold standard; however, comparative data between the dry and wet methods remain limited. We evaluated the efficacy of liposuction and compared outcomes between dry and wet approaches. Our analysis focused on surgical characteristics, complication rates, and clinical outcomes including pain relief, functional improvement, and esthetic satisfaction, with comparisons made between preoperative and 12-month postoperative results. METHODS: Besides surgical data extraction, patient-reported outcome measures (PROMs) were obtained through three different standardized questionnaires to assess pain relief, function gain, and esthetic satisfaction. RESULTS: Both techniques were effective, demonstrating overall improvements in pain, function, and body image, when comparing pre and postoperative outcomes. Lipoaspirate volumes were comparable between the groups. Operative time was significantly shorter in the wet technique group. Short-term complication rates did not differ between dry and wet techniques. While both techniques led to a global improvement, the wet technique showed greater potential in pain reduction and better esthetics satisfaction 12 months post-surgery. CONCLUSION: Lipedema is a complex disease that is still poorly understood. Liposuction may offer symptomatic relief regardless of the technique used, but the wet technique demonstrates better postoperative results, with improved PROMs and fewer complications. The treatment of lipedema requires a multidisciplinary approach, while conservative therapy remains the first-line option, surgical treatment by wet liposuction should be considered for its significant potential in improving functional outcomes and as an effective therapeutic option.

Background/Objectives: Lipedema is a chronic, progressive adipo-fascial disorder characterized by connective tissue dysfunction, fibrosis, microangiopathy, and adipose tissue proliferation. Although lipedema has traditionally been described as a regionally confined disorder, emerging evidence suggests that it may reflect a broader stromal and connective tissue dysfunction. It is therefore plausible that anatomical regions not historically associated with lipedema may also exhibit alterations consistent with this dysfunctional stromal pattern. From this perspective, breast tissue-rich in fibro-glandular and stromal components-represents a compelling model in which to investigate whether such features are present. The breast, with its complex fibro-glandular and stromal architecture, represents a physiologically plausible site of involvement; however, its structural features in lipedema have never been systematically examined. The primary aim of this study was therefore to determine whether breast tissue-rich in fibro-glandular and stromal components-shows recurrent imaging or histopathological features suggestive of lipedema-related involvement. A secondary aim was to compare the frequency of these findings with patterns typically reported in healthy screening populations. Methods: This retrospective cross-sectional study analyzed 62 women (mean age: 44 ± 8 years), obtained between September and November 2025, with a clinical diagnosis of lipedema who voluntarily provided breast imaging reports (ultrasound, mammography, or magnetic resonance imaging, MRI). Results: The findings revealed a remarkably high prevalence of fibro-glandular parenchyma (45%), multiple diffuse cysts (42%), microcalcifications (21%), and fibroadenomas (43.5%), with frequencies substantially exceeding those documented in healthy screening populations. Additional features included significant breast asymmetry or tuberous morphology (6%), reactive or sclero-lipomatous lymph nodes (19%), and recurrent stromal hyperplasia on biopsy. Histological evaluations (n = 9) consistently showed fibroproliferative alterations, including stromal hypercellularity, adenosis, fibroepithelial lesions, apocrine metaplasia, and pseudoangiomatous stromal hyperplasia, suggesting a shared extracellular matrix-related dysplastic phenotype between lipedema-affected breast tissue and peripheral adipose tissue. Conclusions: These findings support the hypothesis that lipedema may express a characteristic breast phenotype driven by stromal and extracellular matrix dysregulation. If confirmed in larger controlled studies, these recurrent alterations could contribute to improved diagnostic frameworks and raise awareness of lipedema as a systemic connective tissue disorder with underrecognized breast manifestations.

INTRODUCTION: Lipedema is a chronic inflammatory disease characterized by symmetrical deposition of adipose tissue in the upper and lower limbs, disproportionate to the trunk. It primarily affects women. The objective of this study was to evaluate the effects of surgical treatment in patients with lipedema who are refractory to conservative management. METHODS: We conducted a systematic review and single-arm meta-analysis in accordance with PRISMA guidelines. Retrospective studies involving patients who underwent surgical treatment after failing clinical management were included. Means and proportions were pooled using the inverse variance method and logit transformations, and heterogeneity was assessed using the I2 statistic. RESULTS: We included 6 studies comprising 429 patients, with follow-up ranging from 6 months to 44 months. In this meta-analysis, surgical treatment with tumescent liposuction resulted in significant clinical improvements for patients with lipedema. The pooled mean preoperative pain score was 5.64 (95% CI: 3.67-8.69), which decreased to 1.19 (95% CI: 0.91-4.22) postoperatively. Sensitivity to touch or pressure was reduced from a preoperative mean of 5.77 (95% CI: 4.10-8.10) to 1.96 (95% CI: 1.17-3.29) after surgery. Swelling scores improved from 5.47 (95% CI: 3.73-8.02) preoperatively to 2.14 (95% CI: 1.31-3.48) postoperatively, while restriction of movement scores decreased from 3.76 (95% CI: 2.48-5.72) to 0.77 (95% CI: 0.36-1.64). CONCLUSION: The results of this single-arm meta-analysis, which included six studies and 429 patients with lipedema refractory to clinical treatment and undergoing surgical intervention, demonstrate that tumescent liposuction is associated with reductions in postoperative pain and edema, as well as improvements in cosmetic outcomes, quality of life, and mobility. The duration of follow-up was adequate to capture relevant clinical outcomes and adverse events. However, lipedema remains a condition that requires further high-quality studies to define the optimal therapeutic approach. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."