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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.

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/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.

Background Lipoedema is a condition of abnormal accumulation of painful adipose tissue, usually in the lower body of women. The disproportionate subcutaneous adipose tissue may negatively impact health-related quality of life (HRQoL). There are currently no patient reported outcome measures (PROM) specifically designed to assess the HRQoL in individuals with lipoedema. The aim of this study was to compare scores on validated lower limb lymphoedema PROMs between females with lipoedema and lymphoedema. Methods In a private lymphoedema clinic in Australia between 1 October 2021 and 22 August 2023, individuals assigned female at birth, aged 18 years and older who consented to the entry of de-identified data into a research databank and completed the Lymphoedema Quality of Life tool (LYMQOL-leg) and/or Lymphoedema Symptoms Intensity and Distress Survey (LSIDS-L) for the legs were included in this study. Between group analysis was conducted on 151 participants who were either diagnosed with lipoedema (N = 90) or bilateral leg lymphoedema (N = 61). Participants with both conditions were excluded. Results Participants with lipoedema reported significantly higher burden scores for symptoms (p = 0.003), appearance (p = 0.003) and mood (p = 0.011) in the LYMQOL-leg survey when compared to participants with bilateral leg lymphoedema. Participants with lipoedema also reported significantly worse LSIDS-L scores for neurological sensation (p = 0.003), biobehavioral (p = 0.016) and resource (p = 0.008) questions compared to participants with lymphoedema. Conclusions This study highlights that although females with lipoedema and lymphoedema experience similar symptoms, their experiences differ in specific outcomes that influence their HRQoL. These findings warrant further investigation into the HRQoL concerns of individuals with lipoedema.

Introduction: Lipedema, a painful disease that almost exclusively affects women, leads to an excessive accumulation of subcutaneous adipose tissue, primarily in the extremities. Morphologically, it is characterized by hyperplasia and hypertrophy of adipocytes as well as by inflammation-associated cells and fibrosis. Limited knowledge exists regarding the background of adipocyte pathology. In the present study, we aimed to identify morphological alterations of lipedema adipocytes, which could cause functional implications in lipedema adipose tissue. Methods: Approximately 3000 adipocytes from nine lipedema and five control adipose tissue samples, originating from non-obese donors, were analyzed. The ratio of atypical nuclei (Lochkerne) in relation to the total amount of nuclei was assessed and compared between lipedema and non-lipedema samples. Results: Lipedema adipose tissue exhibits a significantly higher proportion of Lochkerne compared to controls (p=0.001). While 24% of adipocyte nuclei presented as Lochkerne in lipedema samples, only 3% were identifiable in controls. We further show that the process of Lochkern-formation involves the nuclear indentation by small lipid droplets and their subsequent transmigration through the nucleus towards the central lipid content. Conclusion: The significantly increased occurrence of lipoma-associated Lochkerne in lipedema adipose tissue compared to controls reveals that, from a morphological point of view, lipedema is a form of lipomatosis.

ObjectiveTo analyse and compare the prevalence of comorbidities associated with lipedema in Spanish women with that in the general population.MethodsA cross-sectional study was conducted using an anonymous online questionnaire distributed among lipedema patient associations in Spain. Sociodemographic variables, clinical aspects, and comorbidities were collected. These were then compared with data from the 2023 National Health Survey, which represents the general Spanish population. The prevalence of each pathology was compared using odds ratios (OR) with 95% confidence intervals. Age-group contributions were assessed using standardised residuals from expected/observed contingency tables, considering absolute values >1.96 (95% confidence) to be significant.ResultsA total of 1001 responses were obtained, with a mean age of 44.2 years. The most prevalent comorbidities were vitamin D deficiency (63.4%), lower limb venous insufficiency (47.2%), and migraine (43.1%). Compared to the general female population in Spain, patients with lipedema were more likely to suffer from venous insufficiency (OR= 5.05; 95% CI: 4.3-5.8), urinary incontinence (OR= 4.93; 95% CI: 4.1-5.8), migraine (OR= 3.9; 95% CI: 3.4-4.5), thyroid disease (OR= 2.21; 95% CI: 1.8-2.6), and asthma (OR= 2.09; 95% CI: 1.7-2.5). However, the probability of hypertension (OR= 0.38; 95% CI: 0.2-0.4) and diabetes (OR= 0.36; 95% CI: 0.2-0.6) was significantly lower.ConclusionsSpanish women with lipedema have a higher prevalence of certain pathologies that should be considered in their medical care. Understanding these relationships is crucial to improving the detection and treatment of patients.

BACKGROUND/OBJECTIVES: Lipedema is a chronic and progressive adipose tissue disorder characterized by the abnormal accumulation of subcutaneous fat, predominantly in the legs and occasionally in the arms. The symptom that most significantly affects the quality of life is pain. Ultrasound elastography is an imaging technology that allows for measuring tissue stiffness quantitatively. This study aims to evaluate the relationship between accompanying pain in patients with lipedema and tissue elasticity measured using shear-wave elastography (SWE). METHODS: Our study was designed as an observational, analytical and cross-sectional study. The visual analog scale (VAS) was used to assess pain, while the PainDetect questionnaire was utilized to evaluate neuropathic pain. The evaluation of tissue elasticity and fibrosis was conducted using the SWE method. RESULTS: This research assessed thirty-five patients, revealing an average age of 45.2 years and an average body mass index (BMI) of 33.6 kg/m². 60% of the patients had a lipedema diagnosis in their family history. Both age (p < 0.01) and BMI (p < 0.001) values were moderately correlated with all subcutaneous adipose tissue measurements, while no correlation was observed in SWE measurements. Only the level of the thigh in the SWE-Elasticity (SWE-E) values was related to VAS (r = 0.35, p = 0.03). Additionally, PainDetect scores demonstrated significant positive correlations with both SWE-velocity (SWE-V) and SWE-E measurements in the thigh region. Specifically, SWE-V showed moderate correlations with PainDetect scores in the right thigh (r = 0.38, p = 0.02) and left thigh (r = 0.47, p = 0.004), while SWE-E was also significantly correlated in both the right (r = 0.44, p = 0.007) and left thighs (r = 0.44, p = 0.008). CONCLUSIONS: While SWE measurements were not correlated with skin adipose tissue, SWE measurements were correlated with pain and neuropathic pain in patients with lipedema. This finding highlights a potentially important relationship between tissue elasticity and pain, which may warrant further exploration. SWE offers a novel, non-invasive approach to quantifying tissue stiffness, providing valuable insights into tissue alterations in women with lipedema.

Lipedema is a lipodystrophic disease characterized primarily by a disproportionate increase in lower body subcutaneous fat. Although moderate weight loss decreases lower body fat mass in women with obesity and lipedema, it is possible that this decrease is due to a reduction in normal subcutaneous fat, rather than lipedema-affected fat. We evaluated the effect of moderate (11%) diet-induced weight loss on body fat mass and distribution, assessed by dual-energy X-ray absorptiometry and magnetic resonance imaging, in a 56-year-old woman with lipedema who was normal weight (body mass index: 23.9 kg/m2) at baseline. Approximately 85% of the decrease in body weight comprised body fat. The relative reduction in upper body fat (abdominal subcutaneous, arm and trunk fat) was similar to the relative reduction in lower body (total leg fat and thigh subcutaneous fat). Accordingly, weight loss did not change the proportion of total body fat comprising leg fat (44.8% and 45.1% before and after weight loss, respectively) or arm fat (9.1% and 9.6% before and after weight loss, respectively). These data suggest weight loss decreases lipedema-affected adipose tissue and demonstrate the therapeutic effect of weight loss on body composition in women with lipedema even if they are normal weight.

Introduction & Objectives Lipedema is a chronic and underdiagnosed adipose tissue disorder characterized by disproportionate lower limb fat distribution, pain, and edema. Despite increasing awareness, diagnostic uncertainty persists due to heterogeneous semiological definitions and limited attention to the patient's subjective experience. Methodology This study aims to explore how patients with lipedema verbally represent their symptoms and bodily sensations, and how these narratives correlate with established semiological criteria. By analyzing spontaneous language, we seek to identify potential linguistic markers that could enhance diagnostic characterization and favor earlier recognition of the condition. We conducted an observational, multicenter qualitative study involving adult women with clinically confirmed lipedema. Semi-structured interviews were recorded and transcribed verbatim. Lexical and semantic analyses were performed using natural language processing software and manual thematic categorization. Semiological assessment included tissue consistency, pain distribution, symmetry, and evolution. Cross-analysis explored correlations between verbal descriptors (pain, heaviness, swelling, injustice, shame, sensitivity) and clinical stage or subtype. Results Preliminary findings from revealed recurrent lexical fields expressing bodily dysmorphia, hyperalgesia, and emotional distress. Distinct linguistic patterns emerged according to semiological criteria: patients with stage II–III lipedema frequently used affective and metaphorical language (“weight anchored in my legs”), whereas earlier stages emphasized mechanical sensations (“tension,” “tightness”). A strong convergence was observed between the richness of expressive language and subjective pain scales. Discussion Linguistic analysis of patient verbatim provides novel insight into the semiological complexity of lipedema. Integrating qualitative linguistic descriptors into diagnostic frameworks may refine clinical classification and improve therapeutic communication. Conclusion Linguistic analysis of patient verbatim provides novel insight into the semiological complexity of lipedema. Integrating qualitative linguistic descriptors into diagnostic frameworks may refine clinical classification and improve therapeutic communication. These preliminary results suggest that the words patients use may serve as semiological markers supporting a more holistic understanding of lipedema.

Background: The aim of the study was to verify the effectiveness of a 5-week intensive protocol of multilayer bandaging alone or in combination with diet, applied to the clinical practice of lipedema. Methods: 114 women with lipedema were studied, divided into three groups: 35 women were treated with multilayer bandaging in biweekly sessions for 5 weeks, 48 were treated with the same bandaging protocol combined with an anti-inflammatory diet, and 31 women received no treatment. The effect on anthropometry, lower limb volume, pain caused by the tissue fold, and subjective symptoms were evaluated. Results: Women who completed the 5-week intensive protocol of multilayer bandaging showed a statistically significant reduction in all observed parameters: body weight, waist and hip circumference, lower limb volume, pain, and subjective symptoms. The group of women treated with multilayer bandaging and diet showed a significantly greater reduction in lower limb volume and body weight. The treatments were effective regardless of age, BMI, clinical stage, and the presence of fovea in both groups. The wearing time with the multilayer bandage had a positive correlation in the group treated with bandage in combination with diet. Conclusion: A 5week intensive protocol of multilayer bandaging of the lower limbs is an effective treatment for reducing the symptoms and clinical signs of lipedema at all stages of the disease, even in the absence of edema. Adding nutritional therapy during the bandaging cycle increases the effectiveness of the treatment on the volume of the affected extremities and body weight.

Lipoedema is a chronic adipose tissue disorder mainly affecting women with excess subcutaneous fat deposition on the lower limbs, associated with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is not well studied. We conducted a genome-wide association study (GWAS) for this disorder in a clinically ascertained cohort from Spain and performed a meta-analysis with the UK lipoedema cohort GWAS. We then used the results of this study as a replication of the inferred UK Biobank “lipoedema phenotype” study. Whilst our meta-analysis alone did not identify any genome-wide significant associations, our clinical cohorts provide support for three loci identified through the UKBB study: the chr2q24.3 GRB14-COBLL1 locus (rs6753142, PMETA=1.64x10-6), chr6p21.1 VEGFA locus (rs4711750, PMETA=8.99x10-7) and the chr5q11.2 ANKRD55-MAP3K1 locus (rs3936510, PMETA=1.67x10-5). We identify numerous rare SNPs with strong association signals in our meta-analysis (P<1x10-6) with support in both UK and Spanish datasets, three of which also show nominal support in the UKBB (P<0.05). These findings provide a starting point towards understanding the genetic basis of clinical lipoedema and demonstrate the utility of the interplay of large-scale biobanks genetic data and clinically ascertained cohorts to elucidate the genetic architecture of lipoedema.

Background: Lipedema is a chronic adipose tissue disorder predominantly affecting women and is frequently misclassified as obesity. While its physical manifestations are increasingly recognized, less attention has been paid to eating attitudes and psychological well-being in this population. The objective of this study was to descriptively explore eating attitudes and psychological well-being in women with lipedema.Methods:This exploratory cross-sectional study used an anonymous online survey to describe eating attitudes and psychological well-being in women with lipedema. A total of 47 participants completed the Eating Attitudes Test (EAT-26) and the World Health Organization-5 Well-Being Index (WHO-5). Descriptive statistics were used to summarize screening indicators of disordered eating risk and reduced psychological well-being.Results:Approximately two-thirds of participants scored at or above the EAT-26 screening cut-off, reflecting elevated screening indicators of disordered eating risk. When behavioral risk indicators were included, over 70% screened positive according to EAT-26 criteria. Reduced psychological well-being (as indicated by a WHO-5 score of ≤50) was observed in about one-fifth of the sample.Conclusion:In this exploratory sample of women with lipedema, elevated screening indicators of disordered eating risk and reduced psychological well-being were commonly observed. These findings offer preliminary insights suggesting that eating-related risk and reduced well-being may be prevalent in this population. Further research using larger, clinically verified samples is needed to better understand the psychological aspects of 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 .

Lipoedema is a chronic disorder primarily affecting women. Often mistaken for obesity due to its characteristic build-up of fat cells in the legs and sometimes arms, lipoedema leaves women vulnerable to social stigma. This study investigated the role of fears of compassion and depressive symptoms in the context of weight stigma and internal weight bias in women with lipoedema.

Background Lipedema is characterized by disproportionate gluteofemoral adiposity with anti-inflammatory properties. We hypothesized that this phenotype may confer immunological protection against T-helper 1 (Th1)-mediated autoimmunity ("Immunological Shield Hypothesis"). Objective The objective of this study is to explore whether women with a dual-energy X-ray absorptiometry (DXA)-defined lipedema-like phenotype, characterized by disproportionate gluteofemoral fat accumulation, exhibit distinct immunometabolic profiles and lower prevalence of celiac disease (CD) autoimmunity in a nationally representative sample. Methods The cross-sectional analysis included 3,833 women from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Celiac disease (n=11, 0.56% weighted prevalence) was defined by strict serology (tissue transglutaminase {tTG}-IgA+/endomysial antibody {EMA}-IgA+); lipedema phenotype was defined as leg-to-trunk fat ratio of >90th percentile via DXA. Results Women with celiac disease exhibited 7.4% lower gynoid fat (39.5% versus 42.6%, p=0.0007), persisting in overweight/obese strata. Conversely, the lipedema phenotype demonstrated superior metabolic health: 44.2% lower homeostatic model assessment of insulin resistance (HOMA-IR) (p<0.001) and 7.6% lower neutrophil-to-lymphocyte ratio (NLR) (p=0.012). Conclusions This exploratory population-based analysis identifies phenotypic divergence in fat distribution between the DXA-defined lipedema phenotype and celiac disease autoimmunity, yielding observations consistent with, but not confirmatory of, the "Immunological Shield Hypothesis." While limited by the small number of celiac cases (n=11), a sample size insufficient to detect prevalence differences for a ~7%-9% phenotype, for which approximately 225-600 celiac cases would be required, the observed differences in gynoid adiposity (7.4% reduction, p=0.0007) and the favorable metabolic profile of the lipedema phenotype (44.2% lower HOMA-IR and 7.6% lower NLR) suggest biological plausibility warranting validation in larger, targeted cohorts. These findings motivate targeted studies to evaluate whether dietary exposures, including gluten-related immune activation, interact with gluteofemoral adipose biology in lipedema.