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Background Lipedema is a painful subcutaneous adipose tissue (SAT) disorder that mainly affects women. Patients present fat accumulation in the limbs, especially in the legs. Methods A pilot-controlled clinical trial was conducted on a sample of 18 patients with lipedema, equally divided into a control group (CG) and an experimental group (EG). Both groups were given 10 sessions of diathermy on the inner side of their knees, 10 min of treatment per knee. EG was given the diathermy dose at high-intensity heat, while CG was given sham treatment. Measurement instruments used were circumferential measurements, ultrasound measurements, algometry, VAS, and SF-12 questionnaire. Data were collected at baseline, at the end of the study and 5 weeks later. Results significant reductions in left knee circumference were observed in the EG compared with the CG (p = 0.004 post-intervention and p = 0.017 at follow-up). No significant differences were found in ultrasound, algometry, or VAS measurements within or between groups. Conclusions High-intensity heat diathermy resulted in a reduction in knee circumference, suggesting a potential effect on limb volume.

BACKGROUND: Recent studies have consistently shown that patients with lipedema are at a higher risk for depression and anxiety. The aim of this study is to identify the psychological factors associated with lipedema syndrome (LS) and their link to the patient's psychological symptomatology. METHODS: A mixed-methods approach was employed, combining quantitative and qualitative components. The quantitative component involved anonymous online questionnaires, including a Health and Demographic Questionnaire, the body satisfaction and global self-perception questionnaire (BSGSPQ), the lymphedema quality of life questionnaire (LYMQOL), and the Hospital Anxiety and Depression Scale (HADS). The qualitative component consisted of oral interviews to explore the complexity of the phenomenon. Participants included those with "easy bruising," a waist-to-hip ratio ≤0.7 (W/H), and pain levels ≥4/10 on the visual analogue scale (VAS). RESULTS: Our findings indicate that the level of depression is positively correlated with spontaneous pain (p = 0.002; r = 0.331) and the lack of medical understanding (p = 0.011; r = 0.229). Anxiety scores are inversely correlated with body satisfaction (r = -0.317) and global self-perception (r = -0.393); similarly, depression scores show similar correlations with body satisfaction (r = -0.445) and global self-perception (r = -0.608), all with p value of <0.0001. DISCUSSION AND CONCLUSION: This study highlights significant connections between the physical symptoms and mental health in patients with LS. The more affected the self-perception, the greater the depression and anxiety levels. These multiple contributing factors may explain the decline in quality of life (QOL) and deterioration of mental health. It is therefore crucial to proactively integrate mental health management into the care of LS patients. Future research should focus on identifying concrete, actionable methods to support women experiencing LS.

Lipedema is a chronic adipose tissue condition that primarily affects women. Despite increasing recognition of lipedema, the condition remains poorly understood and lacks standardized diagnostic criteria or confirmatory tests. Variability in definitions and measurement across clinical and research settings impedes comparability across studies, constraining the evidence base needed to support future advances in clinical practice and patient care. To address challenges associated with inconsistent definitions and data collection, the Lipedema Foundation (LF) partnered with clinicians, researchers, and biostatisticians to develop a Lipedema Common Case Report Form (CCRF). The CCRF was designed to be a research data harmonization tool and is not intended to define diagnostic standards or guide clinical treatment decisions. Its development involved review of published lipedema clinical guidelines and collaborative work to define data elements and attributes for inclusion. When they existed, validated or standardized measures were incorporated directly. When no suitable standardized measures were available, an iterative and collaborative process was used to develop lipedema-specific Common Data Elements (CDEs). The initial version of the CCRF was piloted in participants with and without lipedema, and updates based on participant and clinician feedback were incorporated into the CCRF. A biostatistical review evaluated data completeness, quality, and structure, leading to additional refinements. The final Version 1 instrument consists of 682 CDEs organized into four classifications: (1) Core, (2) Supplemental Highly Recommended, (3) Supplemental, and (4) Exploratory. The current version is prepared for dissemination in the field. By disseminating the CCRF broadly and encouraging adoption in all lipedema research beginning in 2026, including all newly initiated LF-funded projects, LF intends to evaluate its use with grantees and iterate systematically to achieve consistent and comparable data collection. The CCRF provides a structured framework for harmonized data collection that may facilitate comparability across studies and support future development of standardized diagnostic and research methodologies.

BACKGROUND: Lipedema is a chronic adipose tissue disorder predominantly affecting women, often misdiagnosed as obesity or lymphedema. Emerging evidence points to microvascular dysfunction and chronic inflammation in its pathophysiology. This study aimed to compare complete blood count (CBC) parameters and derived inflammatory indices between women with lipedema and age-matched healthy controls, focusing on the potential diagnostic value of platelet indices such as PDW and MPV. METHODS: We conducted a retrospective observational study including 45 women with clinically confirmed lipedema and 40 age matched healthy controls. CBC parameters and derived inflammatory indices were compared between groups without adjustment for body mass index (BMI). RESULTS: The study included 45 women with lipedema and 40 healthy controls with similar age distributions. No statistically significant between group differences were observed in complete blood count parameters after correction for multiple comparisons, although PDW and MPV were numerically higher in the lipedema group. CONCLUSION: In this exploratory study, PDW and MPV were numerically higher in women with lipedema than in controls, but these differences lost statistical significance after correction for multiple comparisons. These findings argue against PDW or MPV as standalone diagnostic markers of lipedema and indicate that future research should prioritize larger, BMI-matched cohorts and multimodal approaches that integrate platelet indices with tissue-level or imaging markers.

Objectives: To examine the associations of ultra-processed food (UPF) consumption, dietary inflammatory index (DII), and Mediterranean diet adherence with pain severity, physical quality of life, body composition, and inflammatory markers in women with lipedema. Methods: This cross-sectional study included women diagnosed with lipedema across different disease stages. Dietary intake was assessed using a validated food frequency questionnaire, and foods were classified according to the NOVA system to determine UPF consumption. The dietary inflammatory index was calculated to assess the inflammatory potential of the diet, and Mediterranean diet adherence was evaluated using a standardized scoring system. Anthropometric measurements, body composition parameters, inflammatory markers, pain intensity (VAS), and physical quality of life (SF-12 PCS) were assessed. Multivariable regression analyses were performed to investigate the associations between dietary variables and clinical outcomes. Results: A total of 86 women with lipedema (stage 1: n=36, stage 2: n=33, stage 3: n=17) were included. UPF consumption increased from 28.1% to 41.3% of total energy and DII scores from +1.46 to +3.02 across stages, while Mediterranean diet adherence decreased from 28.2 to 21.3. In parallel, BMI increased from 27.1 to 31.1 kg/m² and body fat percentage from 36.7% to 41.1%. Inflammatory markers also rose across stages (hs-CRP: 3.9 to 6.1 mg/L; IL-6: 3.1 to 4.6 pg/mL). In multivariable models, higher DII scores were associated with increased pain severity (β=0.29, p=0.007) and higher hs-CRP levels (β=0.41, p<0.001), whereas Mediterranean diet adherence was positively associated with physical quality of life (β=0.34, p=0.002). Conclusion: Higher ultra-processed food consumption and dietary inflammatory potential were associated with increased inflammation, pain, and adiposity, whereas greater Mediterranean diet adherence was associated with better physical quality of life in women with lipedema.

Lipedema is a chronic adipose tissue disorder characterised by disproportionate accumulation of subcutaneous fat within specific anatomical depots, most commonly the lower extremities, with relative sparing of the trunk. Despite increasing clinical recognition, the mechanisms underlying the selective vulnerability of particular adipose depots and the progressive tissue remodelling observed in lipedema remain poorly understood. Emerging evidence suggests that lipedema is associated with complex alterations in adipocyte biology, adipose stem and progenitor cell (ASPC) function, immune signalling, vascular integrity, extracellular matrix remodelling, and lymphatic homeostasis, indicating that the disease extends beyond simple fat accumulation. Recent advances in adipose tissue biology have demonstrated that adipose depots are not functionally uniform structures, but rather anatomically distinct cellular ecosystems with unique developmental origins, transcriptional programs, stromal composition, immune niches, and metabolic properties. These depot-specific characteristics may provide an important framework for understanding the regional distribution and progression of lipedema. However, while substantial progress has been made in defining differences between visceral and subcutaneous adipose tissue, heterogeneity between individual subcutaneous depots remains comparatively underexplored despite its likely relevance to disorders of regional adipose expansion. The emergence of single-cell and spatial transcriptomic technologies has transformed the study of adipose tissue by enabling high-resolution mapping of adipocytes, stromal populations, vascular cells, and immune microenvironments within healthy and diseased tissue. These approaches offer an unprecedented opportunity to investigate depot-specific cellular states, intercellular signalling networks, and spatial tissue architecture in lipedema. In this review, we synthesise current evidence regarding tissue remodelling and adipose depot heterogeneity in lipedema and examine how single-cell and spatial omics approaches may advance mechanistic understanding of disease pathophysiology. We further discuss current technical and conceptual limitations within the field and highlight future directions for developing integrated adipose tissue atlases capable of identifying disease-driving cellular programs and therapeutic targets in lipedema.

Background: Lipedema is a chronic adipose tissue disorder with disproportionate fat accumulation in the extremities and is often misdiagnosed as obesity. Although women with lipedema appear to be metabolically distinct from body mass index (BMI)-matched controls, their fasting metabolism remains insufficiently characterized. We therefore aimed to define the metabolic signature of lipedema using serum NMR metabolomics and anthropometric profiling. Methods: We conducted a study with 24 premenopausal women with lipedema and 21 BMI-matched controls. Fasting serum samples were analyzed using NMR spectroscopy and anthropometric data were collected. Regional body composition was additionally assessed in an exploratory matched DXA subset (n=12). To characterize coordinated metabolic differences beyond single analytes, we derived exploratory composite indices and applied multivariate analyses. Results: Despite similar BMI, women with lipedema showed lower waist circumference, waist-to-hip ratio and lower fasting insulin than controls (age-adjusted p=0.032). NMR profiling revealed lower alanine (p<0.001), lactate (p=0.004), pyruvate (p=0.021), and elevated ketone bodies (3-hydroxybutyric acid: p=0.009; acetoacetic acid: p=0.035; acetone: p=0.006). These alterations were reflected by significant group differences in composite indices for fat distribution (g=1.26; p<0.001), glycolysis (g=0.74; p=0.018), and ketone metabolism (g=0.70; p=0.018). Principal component analysis of the selected indices explained 78% of the total variance and showed partial group separation between lipedema and controls. Conclusion: Lipedema is associated with a distinct fasting metabolic profile characterized by reduced glycolytic intermediates, enhanced ketone body signals, and a more peripheral fat distribution despite comparable BMI. These findings support the concept of lipedema as a metabolically distinct phenotype and suggest that multivariate metabolic signatures may help refine future diagnostic and interventional approaches.

Lipedema affects an estimated 11–12% of women worldwide and is characterized by bilateral, symmetric adipose deposition in the lower extremities, disproportionate pressure pain, spontaneous bruising, and resistance to conventional dietary interventions. Despite its prevalence, lipedema lacks a unifying mechanistic framework. Current descriptions treat it as a fat storage disorder with secondary vascular and inflammatory features, leaving critical observations mechanistically unexplained: a highly characteristic quantitative sensory testing (QST) pattern with no published alternative mechanistic explanation, a paradoxical immunological profile, a 35–40% comorbidity with fibromyalgia, a 1.42 relative risk for ADHD, estrogen-dependent onset, and asymmetric expression in the presence of local vascular triggers. We propose the gfWAT-IIT2 framework, which posits that lipedema is fundamentally a syndrome of polarization of the gluteofemoral white adipose tissue (gfWAT) microenvironment toward innate type 2 immunity (IIT2), amplified by estrogen via mast cell estrogen receptors, and generating neuropathic pain through selective histaminergic sensitization of Aδ/C fibers (H1/H4 receptors, PPT↓) and inhibition of Aβ fibers (H3 receptor, VDT↑), with thermal thresholds remaining normal: a triad that is mechanistically explained by histaminergic peripheral sensitization. The gfWAT-IIT2 framework integrates reported clinical, sensory, immunological, and depot-specific observations into a testable mechanistic cascade, generates fourteen falsifiable predictions, and repositions the therapeutic target from adipocyte to mast cell. The framework further proposes that asymmetric lipedema (where one limb expresses the disease more severely due to an identifiable local trigger) constitutes a natural controlled experiment suggesting that local trigger removal may be disease-modifying in selected patients with documented triggers.

BackgroundLipedema is a chronic and progressive disorder of subcutaneous adipose tissue that predominantly affects women and is frequently misdiagnosed as obesity, lymphedema, or venous disease. Increasing evidence indicates that lipedema represents a systemic vascular-lymphatic-inflammatory disorder rather than a cosmetic or metabolic condition. Delayed diagnosis often results in progressive fibrosis, lymphatic dysfunction, chronic pain, and functional impairment.ObjectiveThis review aims to present a structured, clinically applicable framework for the diagnosis and multimodal management of lipedema within phlebology practice, with an emphasis on stage-specific assessment and integrated therapeutic strategies.MethodsA narrative clinical review of peer-reviewed literature in phlebology, vascular medicine, lymphatic disorders, and adipose tissue pathology was conducted. Diagnostic criteria, clinical staging, and differential diagnostic features were synthesized into a practical, stage-based framework. A multilayer therapeutic approach targeting inflammation, lymphatic function, adipose tissue pathology, extracellular matrix remodeling, and post-treatment rehabilitation is proposed.ResultsAccurate diagnosis of lipedema relies primarily on clinical evaluation, including pain assessment, tissue palpation, characteristic fat distribution, and exclusion of lymphedema and simple obesity. Early-stage identification enables effective intervention focused on inflammation control and lymphatic unloading, potentially preventing irreversible fibrosis. Advanced stages require targeted adipose tissue interventions, fibrosis management, and structured rehabilitation to preserve mobility and quality of life.ConclusionLipedema should be recognized as a systemic vascular-lymphatic-inflammatory disorder within phlebology practice. Early diagnosis and implementation of a structured, stage-specific multimodal treatment framework may significantly alter disease progression and reduce the risk of long-term disability.

BACKGROUND: Lipedema is a chronic and progressive adipose tissue disorder that is often misdiagnosed and notoriously resistant to weight loss. Liposuction remains the most effective surgical treatment, but it requires precise technique to preserve the fragile lymphatic system. This study investigates the utility of pre-, intra- and postoperative ultrasound (US) to objectively assess fat reduction and the selective removal of pathological adipose tissue in patients undergoing liposuction for lipedema. METHODS: A retrospective, single-center study of 24 female patients with lipedema who underwent liposuction of the lower extremities. Perioperative US was used to measure the thickness of the superficial subcutaneous fat (D1) and the deep fat layer (D2) at a standardized anatomical site. Intraoperative US was employed to verify that fat aspiration was performed in the correct superficial plane. A paired t-test was conducted to assess the statistical significance of the change in D1 thickness. RESULTS: The mean patient age was 38 years, with a mean BMI of 25.3 kg/m2. The mean volume of liposuction aspirate was 4.5 L. Statistical analysis showed a significant reduction in mean D1 thickness from 9.9 mm preoperatively to 6.3 mm immediately postoperatively (p < 0,05). This reduction was sustained at the 3-month follow-up, with a mean D1 thickness of 5.8 mm. CONCLUSION: Our pilot study suggests that the perioperative use of ultrasound is a valuable tool for objectively documenting the selective fat reduction achieved with liposuction in lipedema patients. Intraoperative US not only enhances surgical precision, but also reduces the risk of complications by confirming correct cannula positioning in the superficial plane. This technique enhances surgical precision by allowing for the quantifiable removal of pathological superficial fat, confirming its potential to improve outcomes with a low complication rate. 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 .

BackgroundLipedema is an adipose disorder associated with multiple impairments. Conservative treatments remain the mainstay of management, yet evidence regarding the effects of physical therapies on clinical, imaging, and body composition outcomes is limited. Radial extracorporeal shock wave therapy (rESWT) has been proposed as a non-invasive therapeutic option, although its impact is not fully established.MethodsThis was a prospective, longitudinal, within-patient study conducted in women with clinically diagnosed lipedema. One lower limb was treated with radial extracorporeal shock wave therapy (rESWT), whereas the contralateral limb served as an internal control. A total of 16 patients were initially assessed, of whom 12 completed the full follow-up and were included in the final analysis. rESWT was applied over six sessions (two sessions per week) using standardized parameters. Clinical outcomes (LEFS, EQ-5D, SF-36 Physical Function, and IPAQ) were assessed at baseline, 6 weeks, and 3 months. Ultrasound and elastography were used to evaluate subcutaneous tissue thickness and stiffness at predefined leg and thigh sites, while segmental bioimpedance analysis assessed body composition and fluid distribution. Longitudinal changes were analyzed using mixed-effects models.ResultsSignificant improvements were observed in functional capacity, quality of life, and physical activity levels at both 6 weeks and 3 months compared with baseline (p < .05). In contrast, no statistically significant changes were detected in ultrasound-derived tissue thickness, elastography measurements, or bioimpedance parameters over time, and no significant differences were detected between treated and control limbs within the constraints of the available sample size.ConclusionsrESWT was associated with meaningful clinical and functional improvements in patients with lipedema, despite the absence of detectable changes in tissue thickness, stiffness, or body composition. These findings suggest that the benefits of rESWT may be mediated through symptom modulation and functional adaptation rather than structural tissue modification, supporting its role as part of conservative, symptom-oriented treatment strategies in lipedema.

Lipedema has long been misclassified as a cosmetic concern or a subtype of obesity, leading to delayed diagnosis and suboptimal surgical outcomes. Growing molecular, histopathologic, and imaging evidence supports lipedema as a systemic disorder involving adipose tissue, connective matrix, vascular–lymphatic integrity, and neuroimmune regulation. To integrate these findings into a clinically actionable model, we introduce the concept of Adipoconnective Fragility Syndrome (AFS), framing lipedema as a multisystem condition with direct implications for surgical planning and perioperative management.

BackgroundLipedema is a chronic, progressive adipose tissue disorder affecting mainly women, characterized by bilateral, disproportionate fat accumulation in the lower extremities. The condition is often associated with pain, heaviness, and functional limitations. While the adipose tissue changes in lipedema are well-described, its impact on muscle mass, strength, and functional performance remains underexplored. This study aimed to evaluate the prevalence of sarcopenia and its relationship with lipedema severity.Materials and methodsA cross-sectional observational study was conducted on 48 women with clinically diagnosed lower-extremity lipedema. Diagnosis followed the International Lipoedema Association and German S2k guidelines. Sarcopenia was assessed using a multidimensional approach, including ultrasonographic rectus femoris thickness, handgrip strength, the Five Times Sit-to-Stand Test, and four-m walking speed. The lipedema stage was determined using morphological criteria. Statistical analyses evaluated the relationships between sarcopenia, functional parameters, and lipedema stage.ResultsParticipants had a mean age of 47.2 ± 8.4 years and a BMI of 33.0 ± 4.3 kg/m2. Sarcopenia was identified in 33.3% of participants, with 14.6% classified as severe. Those with sarcopenia exhibited lower rectus femoris thickness and slower walking speed (p < .05). Advancing lipedema stage correlated with reduced muscle thickness, weaker handgrip strength, slower gait, and prolonged Five Times Sit-to-Stand Test duration (p < .05). Stage 3 patients demonstrated the highest prevalence of sarcopenia, indicating progressive impairment in muscle mass and functional performance with disease severity (p < .05). No significant associations were found between age or BMI and muscle parameters (p > .05).ConclusionsSarcopenia is prevalent in women with lower-extremity lipedema and increases with disease stage. Comprehensive musculoskeletal assessment should be integrated into lipedema management to address functional impairment and optimize patient care.

BACKGROUND: Lipedema is a chronic adipose tissue disorder characterized by abnormal and disproportionate fat accumulation in the extremities, leading to pain, edema, and functional impairment. Liposuction has become a central component of surgical management. However, postoperative complications, particularly seroma formation, remain a concern. OBJECTIVES: To evaluate the incidence of postoperative seroma and associated risk factors in patients undergoing liposuction for lipedema treatment, based on procedures performed by a single surgical team in a single institution. METHODS: This retrospective observational study included 93 female patients who underwent liposuction for lipedema between April 2019 and January 2024. Data collected included demographic variables, body mass index (BMI), anesthesia type, volume of aspirated fat, percentage of body weight removed, use of adjunct technologies (ultrasound or laser), association with other surgeries such as varicose vein surgery, and prior conservative treatment. The primary outcome was the development of postoperative seroma. Statistical analysis included Chi-square and Student's t-tests and multivariable logistic regression, with significance set at p ≤ 0.05. RESULTS: Among 93 cases, 17 patients (18.3%) developed postoperative seroma. Higher volumes of aspirated fat (% body weight) were significantly associated with seroma formation (7.27% vs. 5.84%, p = 0.005). Concomitant minor procedures were also linked to increased seroma incidence (p = 0.035). No seromas occurred in patients treated using ultrasound-assisted liposuction. Minor complications included one infection and one hematoma (1.07%). CONCLUSIONS: Liposuction for lipedema is a safe and effective surgical option with a low rate of major complications, but seroma remains a relatively frequent postoperative finding. Higher aspirated fat volumes relative to body weight and the presence of concomitant procedures increase the risk of seroma. No seromas were observed in the ultrasound-assisted group; however, this difference did not reach statistical significance and should be considered only as hypothesis-generating. Further studies are needed to validate these findings and guide surgical decision-making. 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 .

INTRODUCTION: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat deposition, primarily in the lower extremities, leading to pain, functional impairment, and reduced quality of life. While Power-Assisted Liposuction (PAL) is the standard surgical approach, the integration of Ultrasound-Assisted Liposuction (UAL) with PAL has been proposed to enhance fat removal and improve patient outcomes. OBJECTIVE: To compare the clinical efficacy, postoperative outcomes, and complication rates of PAL alone versus UAL + PAL in patients with Stage II and III lipedema. METHODS: A retrospective cohort study was conducted on 60 female patients diagnosed with lipedema (Stage II and III). 30 patients underwent PAL alone, while 30 received UAL followed by PAL. Primary outcomes included the volume of fat aspirated, circumferential reduction, and postoperative pain, measured at multiple time points over a 12-month follow-up. Secondary outcomes assessed patient satisfaction, time to return to daily activities, and complication rates. RESULTS: The UAL + PAL group demonstrated a significantly higher mean fat extraction volume (5,500 ± 450 mL) compared to the PAL group (4,100 ± 380 mL; p < 0.01). Circumferential reduction was greater in the UAL + PAL group, with an average reduction of 12.5 cm versus 8.2 cm in the PAL group (p < 0.01). Postoperative pain, assessed using a Visual Analog Scale (VAS), was significantly lower in the UAL + PAL group (VAS 4.5 ± 0.7) compared to the PAL group (VAS 6.2 ± 0.8 at 24 hours post-surgery; p < 0.01). Additionally, patients treated with UAL + PAL reported a faster return to daily activities (9.3 ± 1.8 days vs. 12.8 ± 2.1 days; p < 0.01) and higher satisfaction scores (4.8 ± 0.5 vs. 4.2 ± 0.6 on a 5-point Likert scale; p < 0.05). Complication rates were comparable between the two groups, with no major adverse events reported. CONCLUSION: UAL + PAL offers significant advantages over PAL alone in the surgical management of lipedema, providing superior fat removal, reduced postoperative pain, faster recovery, and improved patient satisfaction. These findings support the integration of UAL into standard liposuction protocols for advanced-stage lipedema, emphasizing its efficacy in overcoming the challenges posed by fibrotic adipose tissue. 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 .

BACKGROUND: Lipedema is a chronic, progressive disorder of subcutaneous adipose tissue that mainly affects women. It is characterized by disproportionate fat hypertrophy, pain, bruising, and marked resistance to diet and exercise. Tumescent liposuction remains the only effective treatment to slow or reverse disease progression, but involves large volumes and fragile microvasculature, increasing bleeding risk. OBJECTIVE: This study aimed to evaluate whether perioperative tranexamic acid (TXA) reduces intraoperative blood loss, postoperative bruising, and early complications in lipedema liposuction. METHODS: We retrospectively analyzed 230 staged liposuction procedures for lipedema performed between 2021 and 2024 at a single center. Patients received TXA intravenously, locally, or in combination, or no TXA. Primary outcomes were estimated intraoperative blood loss and postoperative ecchymosis. Secondary endpoints included hematoma, transfusion need, thromboembolic events, infections, and recovery time. RESULTS: All TXA groups showed significantly lower intraoperative blood loss and hemoglobin drop versus controls (p < 0.01). Local and combined routes were most effective, with the combined approach yielding the lowest ecchymosis scores. Hematoma rates dropped from 12% (no TXA) to 0-6.7% (TXA), and no thromboembolic or infectious complications were observed. No TXA-treated patients required transfusions, while 6% of controls did. CONCLUSIONS: TXA use in lipedema liposuction significantly reduces bleeding and bruising without increasing thromboembolic risk. Combined systemic and local administration appears most beneficial. These findings support TXA as a safe, effective adjunct in multistage, high-volume liposuction for lipedema. Prospective trials are needed to confirm the optimal protocol in this unique population. 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 .

Lymphedema and Lipedema are chronic disorders that are often misdiagnosed, leading to complications ranging from infection to impaired mobility. While the genetic basis of lymphedema is well characterized, the genetic contributions to lipedema remain unclear despite clear familial hereditary patterns. This review examines current knowledge on the genetic foundations of both conditions, examining established causative genes in lymphedema and emerging evidence of heritability in lipedema. It also evaluates the role of genetic testing in diagnosis and classification. By emphasizing established findings and highlighting ongoing gaps, this review supports efforts to refine diagnosis and guide therapeutic development.

Background/Objectives: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation, pain, microvascular dysfunction, and low-grade inflammation. Although low-carbohydrate, high-fat (LCHF) dietary approaches are increasingly used in clinical practice, their longer-term associations with vascular, lymphatic, and immunometabolic pathways in lipedema remain insufficiently understood. This preliminary exploratory study evaluated clinical outcomes and circulating mediators during a 7-month LCHF dietary intervention. Methods: Twenty-four women with lipedema (median age: 39 years) underwent a 7-month individualized, calorie-restricted LCHF diet under medical supervision. Outcomes included body mass index (BMI), leg volume, and adipose tissue pain assessed using a visual analogue scale (VAS). Fasting serum samples collected at baseline and follow-up were analyzed for angiogenic, inflammatory, endothelial, and lipid mediators using Luminex assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The intervention was associated with significant reductions in BMI, leg volume, and adipose tissue pain (p < 0.001). These changes were accompanied by increased vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor D (VEGF-D), and angiopoietin-2 (Ang-2), together with decreased pro-inflammatory cytokines and endothelial adhesion molecules. Several endocannabinoid-related lipid mediators, including oleoyl ethanolamide (OEA), arachidonoyl ethanolamide (AEA), and palmitoyl ethanolamide (PEA), also decreased. Baseline OEA and AEA concentrations, as well as reductions in OEA over time, were associated with greater BMI reduction. Change in interleukin-8 (IL-8) showed a nominal association with leg volume reduction, while pain improvement was associated with decreases in P-selectin and VEGF-A and increases in interleukin-13 (IL-13). Conclusions: A 7-month calorie-restricted LCHF dietary intervention in women with lipedema was associated with clinical improvement and changes in circulating vascular, inflammatory, and lipid mediators. These findings reflect systemic changes accompanying the intervention; however, causal relationships and specific mechanisms cannot be established.