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PURPOSE: Individuals with lipoedema may experience negative impacts that are not often identified through current quality-of-life measures. The aim of this study was to explore the experiences of individuals living with pre-existing lipoedema and their perceptions of how these experiences influence quality of life. METHODS: Participants with a prior diagnosis of lipoedema participated in a single semi-structured interview or focus group. These interviews/focus groups were transcribed verbatim, allowing for an inductive thematic analysis to be conducted. RESULTS: Sixteen participants were included and four main themes were identified. These included: the ongoing work of living with lipoedema, living with a restrictive and overwhelming condition, caught between self-acceptance and social judgement, and forced to navigate lipoedema alone. Across the four themes, 21 sub-themes emerged to convey the quality-of-life concerns experienced by individuals with lipoedema. CONCLUSIONS: Individuals living with lipoedema experience impacts on their quality-of-life across physical, psychological, and social aspects of life. This study highlights how the ongoing burden of physical symptoms, social perceptions, and healthcare-related challenges contributes to reduced quality-of-life for individuals living with lipoedema. Increased knowledge and awareness amongst healthcare providers is needed to improve care received by individuals living with this condition.

IntroductionLipedema is a chronic adipose and connective tissue disorder in which pain is classically localized to affected limb tissue. However, some patients report joint, periarticular, myotendinous, or axial pain, with fatigue, sleep disturbance, and exercise intolerance. When symptoms become widespread, the presentation may resemble fibromyalgia (FM), creating a diagnostic challenge for phlebologists.ObjectivesTo provide a clinical framework for distinguishing characteristic lipedema tissue pain from musculoskeletal pain generators, secondary central pain amplification, and potentially coexisting FM.MethodsThis narrative review was conducted with reference to the Scale for the Assessment of Narrative Review Articles (SANRA). PubMed, Scopus, and Google Scholar were searched through May 2026 for studies addressing lipedema, FM, widespread pain, hypermobility, connective tissue vulnerability, biomechanical dysfunction, and pain sensitization. Reference lists were manually screened. No formal risk-of-bias assessment or quantitative synthesis was performed.ResultsCharacteristic lipedema pain is predominantly localized to affected adipose tissue and associated with tenderness, pressure sensitivity, easy bruising, and functional impairment. Observational studies have also reported joint and periarticular pain, axial symptoms, hypermobility, and biomechanical dysfunction in patient subsets. Extra-adipose pain should be assessed separately and not automatically attributed either to lipedema or independent FM. Tissue hypersensitivity, stromal and microvascular alterations, joint instability, and altered biomechanics may represent peripheral pain generators contributing to secondary central amplification. However, observational evidence does not establish whether widespread pain is intrinsic to lipedema, secondary to musculoskeletal dysfunction or central amplification, or reflects coexisting FM.ConclusionsIn patients with lipedema and extra-adipose or widespread pain, phlebologists should assess joint hypermobility, instability, biomechanical dysfunction, and axial or musculoskeletal pain. FM criteria identify a widespread pain phenotype but cannot determine whether it represents an independent comorbidity or is related to persistent peripheral nociceptive mechanisms. Multidisciplinary assessment may improve diagnostic characterization and individualized management.

BackgroundChronic venous disorders and lipedema are complex and frequently underdiagnosed conditions characterized by heterogeneous clinical presentations, progressive tissue remodeling, and substantial variability in treatment response assessment. Despite advances in minimally invasive vascular interventions, longitudinal evaluation in routine clinical practice continues to rely heavily on subjective interpretation, non-standardized comparative imaging, and physician-dependent assessment pathways. The integration of multimodal vascular data into structured longitudinal clinical workflows remains limited.ObjectiveThis study introduces the LipoVena AI Framework, a physician-centered conceptual artificial intelligence-assisted clinical support architecture designed to facilitate multimodal integration, longitudinal treatment-response evaluation, and personalized monitoring in lipedema and chronic venous disease management.MethodsA retrospective observational clinical dataset consisting of 32 patients with chronic venous insufficiency, lipedema, reticular veins, spider veins, and mixed venous-lymphatic phenotypes was reviewed. Standardized standing-position photography, duplex ultrasound imaging, procedural documentation, and longitudinal 1-month follow-up assessments were integrated within a conceptual AI-assisted workflow. Representative patients underwent multimodal minimally invasive treatment strategies including endovenous laser therapy (EVLT), CLACS-guided sclerotherapy, radiofrequency-based tissue remodeling, and compression therapy. The proposed framework conceptually integrates multimodal imaging analysis, vascular mapping, comparative longitudinal assessment, and physician-supervised AI-assisted interpretation.ResultsRepresentative 1-month follow-up observations demonstrated visible improvements in contour harmonization, superficial venous prominence, tissue irregularity, skin texture uniformity, and vascular burden across multiple venous and lipedema phenotypes. Comparative multimodal analysis integrating clinical photography and duplex ultrasound findings enabled structured longitudinal assessment of therapeutic response patterns. Upper-extremity lipedema cases additionally demonstrated measurable contour and tissue-texture improvement following multimodal treatment strategies. The proposed framework illustrated the potential role of AI-assisted longitudinal comparison and multimodal integration in supporting objective treatment-response evaluation within physician-centered vascular care workflows.ConclusionThe LipoVena AI Framework presents a conceptual translational model for future AI-assisted vascular and lipedema medicine by integrating standardized clinical imaging, duplex ultrasound evaluation, multimodal treatment documentation, and longitudinal follow-up analysis within a physician-centered ecosystem. Although prospective multicenter validation and quantitative AI modeling remain necessary, the present framework highlights the potential of explainable and physician-supervised artificial intelligence systems to support personalized, data-driven, and longitudinally optimized vascular care.

RATIONALE: To evaluate which factors are associated with change in lymphedema-specific quality of life (QoL) and relative volume difference in the maintenance phase after a multidisciplinary intensive treatment program in patients with lower limb lymphedema(LLL). METHODS AND RESULTS: In this retrospective study, patients received a multidisciplinary intensive treatment followed by a maintenance phase. In this maintenance phase, patients were advised to perform skin care and exercises and to wear compression garments. Circumferential measurements and the Lymph-ICF-LL questionnaires to determine volume and the lymphedema-specific QoL, respectively, were collected at the start and end of the intensive treatment and at 6 months follow-up. Patient-, lymphedema-, and treatment-related variables were collected to investigate their association with change in lymphedema-specific QoL and relative volume in the maintenance phase. Mann-Whitney U and Spearman rank correlation tests were applied. Patients (n = 279) who did not receive physiotherapy between 5 and 6 months follow-up and had a lower %score on the 6-minute walk test at the start of the intensive treatment showed significant better improvement in physical function and general tasks/household in the maintenance phase, respectively. Younger age, concomitant lipedema, and a lower % volume reduction during intensive treatment were significantly associated with less relative volume increase in the maintenance phase. CONCLUSIONS: Patients without physiotherapy around 5-6 months follow-up or with limited physical capacity at the start may perceive better improvements in certain lymphedema-specific QoL domains, while younger age, concomitant lipedema, and less initial volume reduction appear to be less predisposed to volume regain during the maintenance phase.

BackgroundLipedema is a chronic condition that predominantly affects women and is commonly associated with pain, edema, and functional impairment. Conservative physiotherapy interventions are frequently recommended; however, the scope and characteristics of the available evidence remain unclear.ObjectiveTo map the existing evidence on conservative physiotherapy interventions for lipedema, focusing on intervention types, outcomes assessed, and methodological characteristics.MethodsA scoping review was conducted according to the PRISMA-ScR guidelines. Eligibility was guided by the PCC framework. Electronic databases and gray literature were searched for primary studies and secondary sources addressing conservative physiotherapy interventions for lipedema. Data were synthesized descriptively.Results15 records were included, comprising randomized controlled trials, observational studies, and secondary sources such as reviews, guidelines, and consensus documents. The most frequently investigated interventions were complex decongestive therapy, therapeutic compression, structured exercise programs, and adjunct physical modalities. Outcomes mainly included edema, pain, functional capacity, and quality of life. Among primary studies, multimodal conservative physiotherapy approaches were the most frequently reported. Secondary sources consistently described conservative physiotherapy as a component of care, although they were not treated as independent confirmation of treatment effects.ConclusionThe available literature suggests that conservative physiotherapy is frequently described as a component of lipedema management. However, the evidence base is characterized by methodological heterogeneity, small sample sizes, and the absence of formal quality appraisal, and the findings should be interpreted as a mapping of the available evidence rather than as evidence of treatment efficacy.

ObjectivesTo investigate the clinical and ultrasonographic changes associated with radial extracorporeal shock wave therapy (rESWT) in women with lipedema.MethodsThis prospective, single-arm study included 40 women with lipedema who completed six sessions of rESWT administered twice weekly to the index lower limb. Treatment consisted of 3000-6000 impulses at 15 Hz and 3-4 bar. Participants were evaluated at baseline (T0), immediately after treatment (T1), and at 4-week follow-up (T2). Outcomes included visual analog scale (VAS) pain scores, Patient-Reported Outcomes Measurement Information System (PROMIS) scores, pressure pain threshold (PPT), limb circumference, subcutaneous fat thickness (SCFT), and tissue echogenicity. Patient Global Impression of Change (PGIC) was assessed at T1 and T2.ResultsVAS scores decreased from 8.45 at T0 to 5.45 at T1 and 4.17 at T2, while PROMIS scores decreased from 25.3 to 16.2 and 14.3, respectively (both p < .001). PPT increased significantly at all four evaluated sites (p < .001). Calf and thigh circumferences decreased significantly over time (both p < .001). Medial calf SCFT decreased from 16.5 to 15.2 and 15.1 mm, and medial thigh SCFT from 21.0 to 18.2 and 18.1 mm (both p < .001). Median tissue echogenicity decreased from 3 at baseline to 2 at both post-treatment assessments (p < .001). PGIC scores also improved between T1 and T2 (p < .001).ConclusionsSix sessions of rESWT were associated with improvements in pain, quality of life, mechanical pain sensitivity, limb circumference, and ultrasonographic tissue characteristics in women with lipedema, with most improvements maintained at 4-week follow-up. These findings support further evaluation of rESWT as an adjunctive conservative treatment for lipedema in controlled studies with longer follow-up.Trial registrationClinicalTrials.gov, NCT07683559.

ObjectivesLipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation, lower extremity pain, functional impairment, and reduced quality of life. Although pain is a cardinal symptom, its underlying mechanisms remain incompletely understood. This study aimed to characterize sensitization-related pain phenotypes in women with lipedema by examining central sensitization (CS) and neuropathic -like pain features and their associations with lower extremity function, sleep quality, and health-related quality of life (HRQoL).MethodsIn this cross-sectional case-control study, 54 women with clinically diagnosed lipedema and 48 age-matched control participants were enrolled between March and October 2025. Pain phenotypes were assessed using the Central Sensitization Inventory (CSI) and Pain-DETECT questionnaire. Lower extremity function, sleep quality, and HRQoL were evaluated using Lower Extremity Functional Scale (LEFS), Jenkins Sleep Scale (JSS), and EuroQol-5D-3L (EQ-5D-3L), respectively.ResultsWomen with lipedema had significantly higher Pain-DETECT and CSI scores than controls, indicating greater neuropathic-like pain features and CS-related symptom burden (both p < .01). They also demonstrated poorer lower extremity function, greater sleep disturbance, and lower HRQoL. Pain-DETECT scores were positively correlated with CSI, anxiety, depression, and sleep disturbance scores. In multivariable analyses, LEFS independently predicted Pain-DETECT scores (B = -0.171, p = .015), whereas anxiety independently predicted CSI scores (B = 1.980, p = .002).ConclusionsWomen with lipedema exhibit prominent sensitization-related pain phenotypes associated with functional impairment, sleep disturbances, and reduced quality of life. Identification of these pain characteristics may improve clinical assessment, patient stratification, and multidisciplinary management of lower extremity symptoms in lipedema.

ObjectivesTo determine the prevalence of chronic venous insufficiency (CVI) in patients with lipedema, characterize venous reflux patterns and CEAP clinical classes, and evaluate associations with demographic and lipedema-related characteristics.MethodsThis retrospective, single-center observational study included adults with lipedema evaluated between January 2023 and December 2025. Of 120 patients screened, 50 were excluded because of incomplete venous Doppler ultrasonography, clinical, or demographic data, leaving 70 patients for analysis. Demographic and clinical characteristics and lower-extremity venous duplex ultrasonography findings were reviewed. Superficial, deep, and perforator reflux; segment-specific reflux; great saphenous vein (GSV) and small saphenous vein (SSV) diameters; laterality; and CEAP clinical class were recorded. Pathological reflux was defined as reversed flow lasting >0.5 s in superficial truncal veins and >1.0 s in the common femoral, femoral, and popliteal veins. Univariable and multivariable logistic regression analyses examined factors associated with CVI.ResultsCVI was identified in 38 of 70 patients (54.3%; 95% confidence interval, 41.9%-66.3%). Venous reflux predominantly involved the superficial system, with GSV reflux as the most frequent segment-specific finding, whereas deep venous reflux was uncommon. Patients with CVI had greater GSV and SSV diameters than those without CVI (both p < 0.001), while age, body mass index (BMI), and disease duration did not differ between groups. CVI frequency increased across BMI categories, although the overall categorical association was not significant. Lipedema stage was not associated with CVI or individual reflux patterns; however, increasing lipedema stage showed a weak positive association with higher CEAP clinical class. Age, BMI, and lipedema stage were not independently associated with CVI in multivariable analysis.ConclusionsVenous insufficiency was frequently observed in patients with lipedema and predominantly involved the superficial venous system. Greater saphenous vein diameters provided an objective ultrasonographic correlate of venous involvement. Because an appropriately matched local control population was not available, the present study cannot establish whether venous reflux is more frequent in patients with lipedema than in the general population. The observed relationship between lipedema stage and CEAP clinical class should therefore be considered hypothesis-generating and warrants confirmation in prospective controlled studies.

ObjectiveThis study aimed to comparatively evaluate sleep quality in individuals with lipedema and healthy controls. In addition, the relationships between sleep quality and depression, anxiety, fatigue, and clinical parameters were investigated.MethodsThis cross-sectional study included 30 women with lipedema and 30 healthy female controls aged 18-75 years. Pain severity in individuals with lipedema was assessed using the Visual Analog Scale (VAS). Lipedema stage, comorbidities, and symptom duration were also recorded. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI), depressive and anxiety-related symptoms were assessed using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), and fatigue severity was evaluated using the Fatigue Severity Scale (FSS).ResultsIndividuals with lipedema had significantly higher BDI, BAI, and FSS scores than controls (all p < 0.001 except BDI, p = 0.001). Sleep quality was significantly poorer in the lipedema group (p < 0.001). Among PSQI subcomponents, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, and daytime dysfunction were significantly worse in individuals with lipedema, while sleep medication use was similar between groups (p > 0.05). In the lipedema group, PSQI scores were positively correlated with depressive (r = 0.489, p = 0.006) and anxiety symptoms (r = 0.386, p = 0.035). No significant associations were found between sleep quality and age, anthropometric measurements, education duration, pain severity, lipedema stage, symptom duration, or fatigue severity.ConclusionsThis study demonstrated poorer sleep quality in individuals with lipedema compared to healthy controls. Sleep quality was also associated with depressive and anxiety-related symptoms, highlighting an association between psychological symptoms and sleep problems in individuals with lipedema.

ObjectivesThis study aimed to determine the frequency of probable lipedema among women with lower extremity pain (LEP) using a validated screening questionnaire and to examine its associations with neuropathic pain (NP) characteristics, functional status, psychological symptoms, and health-related quality of life (HRQoL).MethodsThis prospective questionnaire-based case-control study included 133 women, comprising 68 women with LEP and 65 age-matched healthy controls. Participants were evaluated using the Lipedema Screening Questionnaire (LSQ), Lower Extremity Functional Scale (LEFS), Hospital Anxiety and Depression Scale (HADS), PainDETECT questionnaire, and 12-Item Short Form Health Survey (SF-12). An LSQ score of ≥8 was classified as probable lipedema, whereas a score of ≥12 was classified as high-probability lipedema. These categories indicate screening probability rather than a confirmed clinical diagnosis of lipedema. Group comparisons, correlation analyses, and multivariable regression analyses were performed to examine factors associated with LSQ and LEFS scores.ResultsWomen with LEP had significantly higher LSQ scores and a greater proportion of probable lipedema (36.8% vs 12.3%, p = .001) and high-probability lipedema (19.1% vs 3.1%, p = .003) than controls. Compared with controls, women with LEP had poorer lower extremity function, greater anxiety symptoms, more prominent NP characteristics, and lower physical and mental HRQoL scores (all p < .05). Higher LSQ scores were positively correlated with PainDETECT scores (r = 0.446, p < .001), whereas pain intensity was not significantly correlated with the evaluated clinical outcomes. In multivariable linear regression, PainDETECT score was independently associated with LSQ score (β = 0.382, p = .004). For functional status, both the SF-12 physical (β = 0.352, p = .001) and mental component scores (β = 0.362, p = .002) were independently associated with LEFS scores.ConclusionsProbable lipedema was more frequently identified by LSQ among women with LEP than among healthy controls. NP characteristics were independently associated with greater lipedema-related symptom burden, whereas lower extremity function was independently associated with both physical and mental HRQoL. These findings support the use of lipedema and NP screening as complementary components of the clinical assessment of women with LEP. However, LSQ findings should not be interpreted as a clinical diagnosis of lipedema and require confirmation through appropriate clinical assessment.

Background/Objectives: Lipedema is an adipose tissue disorder associated with body-related burden. This study compared orthorexic eating tendencies between women with and without lipedema and examined associations with body-shape concern and psychological symptoms. Methods: This controlled cross-sectional study included 44 women with lipedema and 44 women without lipedema. Participants completed the Düsseldorf Orthorexia Scale (DOS), Body Shape Questionnaire (BSQ), and Hospital Anxiety and Depression Scale (HADS). Associated variables were examined using multiple linear regression. Results: Women with lipedema had higher DOS scores than women without lipedema (25.07 ± 6.55 vs. 20.48 ± 5.05; Cohen's d = 0.79; p < 0.001). BSQ, HADS-Anxiety, and HADS-Depression scores were also higher in the lipedema group (all p ≤ 0.001). DOS and BSQ scores were positively correlated in both groups. In the multivariable model, which included group status, age, BMI, BSQ, HADS-A, and HADS-D scores, BSQ score was independently associated with DOS score (B = 0.067; 95% CI 0.025-0.108; p = 0.002), whereas group status and the other covariates were not. The model's adjusted R2 was 0.234. Conclusions: Women with lipedema exhibited greater orthorexic eating tendencies, body-shape concern, and psychological symptoms than controls. Body-shape concern was independently associated with orthorexic eating tendencies. The group difference in DOS scores is largely explained by the higher BSQ scores accompanying lipedema; this should not be interpreted as indicating that lipedema is unrelated to orthorexic tendencies. These findings support consideration of body image when addressing eating behavior in lipedema care.

OBJECTIVE: To compare the efficacies of extracorporeal shock wave therapy (ESWT) and complex decongestive therapy (CDT) in patients with lipedema. DESIGN: This randomized-controlled-study included 33 patients with lipedema, with 11 patients in each of the three groups. The first group received ESWT alone, the second group received CDT alone, and the third group received ESWT followed by CDT within the session for six treatment sessions. Assessments were performed at baseline and two weeks after treatment completion. Outcome measures included total and lower extremity fat mass assessed using dual-energy X-ray absorptiometry, lower extremity volume, body mass index, pain intensity, pressure pain threshold, and quality of life. RESULTS: Total and lower extremity fat mass decreased significantly only in the ESWT and ESWT+CDT groups (P<0.05), although the magnitude of improvement was small and not superior to that of CDT alone (P>0.05). Additionally, all three groups showed significant improvements in lower extremity volume, pain intensity, pressure pain threshold, and quality of life (P<0.05), with no significant differences between the groups (P>0.05). CONCLUSION: All three treatment approaches are safe and feasible options for the management of lipedema. Considering its low cost, accessibility, and ease of application, ESWT may be preferred over the other treatment modalities.

BackgroundLipedema is a frequently misdiagnosed chronic condition that significantly impacts patients' quality of life. As artificial intelligence (AI)-based large language models (LLMs) become increasingly integrated into healthcare communication, their accuracy and consistency in providing patient-centered information require thorough evaluation, especially in rare diseases like lipedema. Therefore, this study aimed to evaluate the accuracy and reproducibility of responses generated by ChatGPT, DeepSeek, and Gemini to questions frequently asked by patients with lipedema.MethodsThis cross-sectional study assessed the accuracy and reproducibility of responses generated by ChatGPT, DeepSeek, and Gemini to 25 commonly asked lipedema-related questions. Each model was queried twice in separate sessions, and answers were evaluated by three independent experts using a four-point rating scale. To ensure the objectivity and consistency of expert evaluations, inter-rater agreement was assessed using Cohen's kappa coefficient.ResultsDeepSeek achieved the highest proportion of comprehensive and correct responses (72%), followed by Gemini (64%) and ChatGPT (56%). Accuracy varied across content categories, with notable limitations particularly in treatment, follow-up, and maintenance questions. Reproducibility analysis revealed that DeepSeek produced the most consistent responses across sessions, while ChatGPT and Gemini showed more variability, particularly in treatment and quality-of-life questions. Cohen's kappa values indicated high inter-rater agreement overall, with perfect agreement in some categories for ChatGPT and DeepSeek.ConclusionsLLMs can provide generally accurate and consistent responses to patient-centered questions about lipedema, particularly in areas related to general information and diagnosis. However, reduced accuracy and reproducibility in complex clinical domains suggest that expert oversight is essential when using these tools for patient education.

IntroductionAfter unification of diagnostic criteria for lipedema through guidelines and consensus documents as a fat-disproportion between abdomen and extremities with pain in the affected area, reduced by compression, expensive treatment options like liposuction should be reserved to affected women. Whilst the diagnosis of lipedema is obviously clinic, technical investigations or clear cut-offs shall help avoiding misuse of resources. The aim of this study was to find differentiation criteria between lipedema (LIP) controls (CO).MethodsInvestigator initiated exploratory investigation of 20 women per group, with interim analysis after completion of investigation of 10 women per group. 14 LIP and 12 CO were investigated with QOL-questionnaires (CIVIQ and Lymph), Wunstorf-Vein-Office anamnesis questionnaire, Visual Analogue Scale (VAS) of spontaneous pain, Pain under manual investigation, pain under compression cuffs, ultrasound of skin and subcutaneous fat tissue, share-wave-elastography, water content of skin (LymphScanner) and stiffness of skin (FibroScanner).ResultsStatistical evaluation between LIP and CO presented significant differences for all parameters excepting share-wave-elastography, water content and stiffness of the skin. Differences between controls and Lipedema were achieved with p < .0001 for the Wunstorf-Vein-Questionnaire, with p < .001 for CIVIQ (cut-off >40 Points for LIP), compression cuff (cut-off <60mmHG), with p < .01 Skin thickness (skin lateral thigh >2.1 mm in LIP), fat tissue thickness (ankle >18 mm).ConclusionThis first analysis could establish a series of clear cut-off values between lipedema and controls for medical history parameters (existence of pain and compliance with compression garments), pain sensitivity to palpation and pressure, and the results of at least one quality-of-life questionnaire (CIVIQ better than Lymph-QOL) and promising cut-offs for objective, technically measurable parameters, such as skin and subcutaneous fat thickness. The possibility to discriminate between lipedema and lipohypertrophy will be assessed in the second part of the investigation.

A previously healthy 35-year-old woman developed recurrent syncope and dyspnoea two days after extensive thigh liposuction for lipedema. CT pulmonary angiography revealed a large saddle embolus with peripheral emboli. Fat embolism was initially suspected; however, imaging findings and laboratory parameters supported a thromboembolic origin. Treatment with anticoagulation was complicated by postoperative bleeding. This case report highlights the importance of considering both fat embolism and thromboembolic pulmonary embolism after liposuction.

BACKGROUND: Lipedema is a chronic adipose tissue disorder that may involve the upper extremities, particularly in advanced disease stages, leading to pain, heaviness, and functional complaints. While liposuction is an established treatment for symptom relief and volume reduction, its impact on objective upper-limb function-especially shoulder mobility-has not been systematically evaluated. METHODS: A prospective observational cohort study was conducted in female patients with upper-extremity lipedema undergoing circumferential arm liposuction. Active shoulder range of motion (ROM), including abduction, flexion, and external rotation, was assessed preoperatively and at 1, 3, 6, and 12 months postoperatively using standardized digital goniometry. Upper-limb disability (QuickDASH), pain, perceived heaviness, and upper-arm circumference were also recorded. Outcomes were analyzed over time and stratified by lipedema stage. RESULTS: Sixty-eight patients completed the 6-month primary follow-up. Mean active shoulder abduction improved significantly from 132.4° ± 13.8° at baseline to 154.7° ± 11.5° at 6 months and remained stable at 12 months (p < 0.001). Composite shoulder ROM demonstrated a similar progressive improvement. Patients with Stage II and III lipedema exhibited greater absolute functional gains, achieving postoperative ROM values comparable to those observed in earlier stages. QuickDASH scores, pain, and perceived heaviness decreased significantly over time (p < 0.001). Upper-arm circumference reduction correlated moderately with improvements in shoulder abduction (r = 0.42, p < 0.01). Measurement reliability was excellent (ICC ≥ 0.93). CONCLUSIONS: Upper-extremity liposuction for lipedema is associated with significant and durable improvements in shoulder mobility and upper-limb function. Beyond symptom relief and contour improvement, surgical debulking appears to restore functional movement, supporting the concept of upper-extremity lipedema as a functional disorder. Objective assessment of shoulder mobility should be considered an important outcome measure in the surgical evaluation of lipedema. 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 common, female-predominant disorder characterized by disproportionate, painful lower-limb adipose tissue, and it still lacks an objective biomarker, a disease-modifying therapy, or consensus on whether its core lesion is inflammatory. Its molecular literature is openly contradictory, reporting both immune enrichment and immune down-regulation in the same gluteofemoral depot. Because the dominant morbidity is pain rather than adipose mass, this ambiguity carries direct clinical cost. We therefore asked the following three questions: whether the reported molecular hallmarks survive control for cell-type composition, whether pain and adipose volume behave as separable endpoints, and what the germline architecture implies about the primary lesion. MATERIALS AND METHODS: From a theory-neutral standpoint, we reprocessed the largest publicly deposited adipose bulk RNA-seq dataset of lipedema (14 women with lipedema versus seven controls, paired by depot) with Salmon (College Park, MD: University of Maryland) and DESeq2 (Seattle, WA: Bioconductor Project), estimated cell-type composition by single-sample gene-set enrichment (ssGSEA), and refitted differential expression with leukocyte and erythroid composition covariates to test identifiability. We also synthesized published treatment cohorts (pain versus volume) and reviewed the architecture of germline genome-wide association studies (GWAS). RESULTS: There is no transcriptional lipolytic brake (ADRA2A +0.001; lipases unchanged or mildly up). The apparent immune down-regulation is not identifiable from blood content; adjusting for tissue composition reduces genome-wide-significant genes from 1,501 to four, with blood content correlated with disease at r approximately -0.7, so bulk data can neither establish nor exclude immune involvement, including the NLRP3 inflammasome. Pain and adipose volume are dissociable across treatments, so body weight is a confounded endpoint. The germline architecture reported to date (GRB14-COBLL1, VEGFA, RSPO3, ADAMTS9) is adipo-vascular and extracellular-matrix-based rather than immune, although the largest contributing study defined cases by a bioimpedance proxy rather than by clinical diagnosis. CONCLUSIONS: Lipedema's inflammatory status is currently undecidable from composition-confounded bulk tissue rather than settled, which explains the field's contradictory literature; the germline evidence, limited by its case definitions, supports as a hypothesis an adipo-vascular and connective program rather than a primary immune lesion; and pain, not weight, should anchor trials. We specify, but do not perform, the single decisive experiment - paired thigh-versus-abdomen single-nucleus RNA-seq with explicit composition control.

PURPOSE: This study aimed to compare 12-week changes in body composition and anthropometric parameters between standard-dose and lower-dose tirzepatide escalation regimens in women with lipedema, with particular emphasis on changes in fat mass and skeletal muscle mass. PATIENTS AND METHODS: This retrospective observational study included 100 women with lipedema receiving tirzepatide during routine clinical care. Participants were classified into lower-dose (n = 50) and standard-dose (n = 50) groups according to their prescribed dosing regimens, which differed in cumulative drug exposure. Body composition, anthropometric measurements, and skinfold thickness were assessed at baseline and after 12 weeks. An exploratory composite responder criterion was defined as a ≥5% reduction in fat mass combined with a <5% reduction in skeletal muscle mass, as estimated by bioelectrical impedance analysis (BIA). Between-group comparisons were unadjusted. RESULTS: Both regimens were associated with reductions in body weight, fat mass, and body fat percentage (all within-group p < 0.001). No statistically significant between-group differences were detected in these changes. The lower-dose regimen was associated with a smaller reduction in BIA-estimated skeletal muscle mass than the standard-dose regimen (-0.7 vs. -2.0 kg; p < 0.001). The exploratory composite responder criterion was met by 68% (34/50) of participants in the lower-dose group and 22% (11/50) in the standard-dose group (OR = 7.53; 95% CI: 3.08-18.44; p < 0.001). No statistically significant between-group differences were detected in anthropometric measurements or skinfold thickness changes. CONCLUSION: Both tirzepatide dosing regimens were associated with reductions in body weight and adiposity in women with lipedema. The lower-dose regimen was associated with a smaller reduction in BIA-estimated skeletal muscle mass and a higher proportion of participants meeting the exploratory composite responder criterion. These findings require confirmation in prospective controlled studies, given the non-randomized design, differences in cumulative drug exposure, and potential residual confounding.