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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.

Abstract - Lipedema is a chronic and often debilitating adipose tissue disorder that primarily affects women. The disease is characterized by disproportionate and symmetrical accumulation of subcutaneous fat in the extremities. Despite the high prevalence of lipedema, which affects ~10% of women, and its significant impact on patient quality of life, lipedema is understudied and often misdiagnosed as other disorders (obesity or lymphedema). In this review, we explore the current understanding of lipedema through clinical, tissue, and cellular lenses, and examine suspected pathological mechanisms, including hormonal influences (such as estrogen), adipocyte hypertrophy and hyperplasia, increased extracellular matrix (ECM) fibrosis, and specialized immune cell involvement, including M2 macrophage infiltration. Recent advancements in adipose tissue engineering, including organoids, fat-on-a-chip platforms, and the use of induced pluripotent stem cells (iPSCs) are explored as platforms to study lipedema pathogenesis.

Lipedema is a chronic, female-predominant disorder of subcutaneous adipose tissue characterized by disproportionate fat expansion, pain, and fibrosis. Despite its high prevalence, the cellular mechanisms underlying lipedema remain poorly understood. While the clinical features have been extensively described, its biology of adipose tissue dysfunction and aberrant intercellular communication is still unclear. In comparison to obesity, lipedema is marked by local dysregulation of adipocyte–stromal and adipocyte–vascular interactions. In this minireview, we discuss emerging mechanistic concepts from a cell biology perspective that are particularly relevant to lipedema, focusing on (i) organelle contact site dynamics in adipocytes and their role in lipid handling and stress adaptation; (ii) extracellular vesicle (EV)–mediated crosstalk between endothelial cells, adipocytes, and immune cells as a driver of localized inflammation and fibrosis; and (iii) estrogen-linked signaling pathways that may imprint EV cargo and cellular behavior in a sex-specific manner. By integrating these perspectives, we highlight open experimental settings and mechanistic parallels to other adipose tissue pathologies that help understanding lipedema as a distinct cellular and molecular entity. Investigating how organelle biology, extracellular vesicles communication and hormonal context intersect in adipose tissue may uncover novel biomarkers and therapeutic entry points for this long-neglected condition.

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.

Lipedema is a chronic, progressive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, pain, edema, and resistanc...

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 &gt;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&lt;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.

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 .