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Validation and reliability of the Turkish version of the lipedema screening questionnaire - Turkish Journal of Physical Medicine and Rehabilitation

Background Lipedema is a chronic medical condition primarily affecting women, characterized by bilateral, symmetrical, disproportionate fat deposition in the lower limbs, and sometimes arms and lower trunk. Pharmacological interventions remain limited, but glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs) could provide potential therapeutic benefit due to their effects on weight, metabolism, pain, and inflammation. Methods This was a cross-sectional, patient-reported online survey study comparing self-reported lipedema symptom severity, medication use history, and physical and mental health outcomes across three groups of women with lipedema stratified by GLP-1/GIP receptor agonist medication use status (current users, discontinued users, and never-users). The survey captured demographics, lipedema characteristics, medication use history, and intensity of lipedema symptoms. Additionally, the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health-10 (PROMIS-10) instrument was used to assess physical and mental health. Analyses compared current users, discontinued users, and never-users of GLP-1/GIP RA medications. Results Of 2852 respondents, 2719 met inclusion criteria for analysis. Most participants (99.7%) identified as female, with a mean age of 52.4 years. Approximately 55% were current GLP-1/GIP RA users, most commonly taking tirzepatide. The primary reported reason for medication use was weight management (67.2%), followed by lipedema symptom management (19.3%). PROMIS-10 scores demonstrated higher physical and mental health ratings among current users compared with never-users (median Global Physical Health (GPH): 42.3 vs. 39.1; Global Mental Health (GMH): 44.9 vs. 40.8). Participants recalled improvements in both general health and lipedema symptoms after starting medication. Symptom severity scores for pain, swelling, and functional limitation were consistently lower among current users. Conclusions Self-reported participant responses indicated improved health and symptom severity while using GLP-1/GIP RA medication. These findings support further investigation of GLP-1/GIP RA medications as potential therapeutic options for lipedema.

Lipedema is a chronic disorder characterized by the abnormal and disproportionate accumulation of painful subcutaneous adipose fat, primarily affecting the lower limbs and occurring almost exclusively in women. The aim of this controlled cross-sectional study was to compare body image, psychological distress, and psychological well-being in women with (n = 77) and without lipedema (n = 32). Psychological functioning was assessed using validated measures of depressive symptoms (PHQ-9), eating attitudes (EAT-26), perceived stress (PSS), medically unexplained symptoms (M.U.S.), psychological well-being (WHO-5), life satisfaction (SWLS), psychological flexibility (AAQ-II), pain intensity (VAS), together with measures of body image, lifetime psychological burden, maladaptive cognitive beliefs, symptom severity, and anthropometric parameters. Compared with controls, women with lipedema reported significantly greater body image dissatisfaction, perceived distress, M.U.S., depressive symptoms, disordered eating attitudes, and pain, together with lower psychological well-being, life satisfaction, and psychological flexibility (all p < 0.001). Within the lipedema group, PHQ-9 scores were significantly predicted by M.U.S. scores, maladaptive cognitions, and pain intensity (VAS), whereas EAT-26 scores were predicted by PHQ-9 scores and maladaptive cognitions. These findings indicate that lipedema is associated with a substantial psychological burden and support integrating psychological assessment and intervention into multidisciplinary care.

Background: Lipedema is a chronic disorder of subcutaneous adipose tissue characterized by symmetrical fat accumulation in the extremities, pain, and orthostatic edema. Objectives: This study aimed to assess whether high-resolution cutaneous ultrasound can detect measurable tissue-level changes in subcutaneous tissue over six months. Methods: A retrospective, single-center, real-world longitudinal observational cohort study was conducted in 60 women with lipedema followed at three timepoints (baseline, 3 months, 6 months). High-resolution ultrasound (18–20 MHz) measured subcutaneous and dermal thickness at standardized anatomical sites. Results: All primary ultrasound parameters decreased significantly over six months of conservative multicomponent management, which included individualized nutritional counseling and physical activity. Medial proximal thigh subcutaneous thickness declined by 18.7% (48.2 to 39.2 mm; p < 0.001). Edema prevalence fell from 100% to 55.0%. Echogenicity improved significantly between 3 and 6 months, suggesting a delayed structural remodelling effect distinct from early volumetric reduction. Ultrasound reductions were inversely correlated with weight loss, suggesting that ultrasound captures tissue-level information not fully reflected by anthropometric measures alone. Conclusions: Standardized cutaneous high-resolution ultrasound detected consistent tissue-level modifications over six months of routine clinical follow-up, capturing changes beyond anthropometric measures and representing a candidate monitoring tool warranting evaluation in controlled study designs.

Objective: Lipedema is a chronic adipose tissue disorder characterized by bilateral and symmetrical subcutaneous fat accumulation, predominantly affecting women. Because it is frequently confused with obesity and lymphedema, diagnosis may be delayed. This proof-of-concept study aimed to evaluate the feasibility of LipoAssist, a structured GPT-4–based clinical workflow designed for the preliminary assessment of lipedema under simulated conditions. Methods: Ten simulated clinical scenarios representing lipedema and relevant differential diagnoses were evaluated using LipoAssist. The workflow was designed to obtain a structured medical history, assess clinically relevant symptoms, and generate a standardized case summary. Three board-certified Physical Medicine and Rehabilitation specialists independently evaluated the AI-generated outputs using a 5-point Likert scale across six criteria. A total of 180 ratings were analyzed. Inter-rater agreement was assessed using the intraclass correlation coefficient and Kendall's coefficient of concordance. Results: The overall mean performance score was 3.55 ± 0.64. The highest scores were observed for correct understanding of the clinical condition (4.63 ± 0.49) and identification of the most likely diagnosis (4.53 ± 0.51). Lower scores were recorded for recommendations regarding further diagnostic evaluation (2.17 ± 0.83) and assessment of surgical necessity (1.93 ± 0.64). Case-summary clarity and adequacy of history taking received mean scores of 3.87 ± 0.63 and 3.73 ± 0.64, respectively. Inter-rater agreement was good (ICC = 0.82; 95% CI: 0.68–0.91), and Kendall's W was 0.79. Conclusion: LipoAssist demonstrated promising performance in structured history taking, organization of clinical information, and identification of the most likely diagnosis in simulated lipedema scenarios. However, its performance was limited in advanced diagnostic recommendations and surgical decision-making. These findings support the feasibility of a structured GPT-4–based workflow under simulated conditions but do not establish clinical validity, diagnostic accuracy, or readiness for routine implementation.

BACKGROUND: Lipedema is a chronic disorder characterized by excessive, bilateral, and symmetrical deposition of subcutaneous adipose tissue, predominantly in the lower extremities. Despite its prevalence, lipedema is frequently misdiagnosed as lymphedema, and lymphoscintigraphy is commonly used to differentiate between the two. This systematic review synthesizes the available evidence regarding the most common lymphoscintigraphy findings in patients with lipedema. METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed across the MEDLINE/PubMed, Embase, and Web of Science databases. Studies were included if they reported lymphoscintigraphy findings in patients with lipedema and provided a clear description of the imaging protocol. Extracted data included patient demographics, lymphoscintigraphy protocols, and imaging findings. RESULTS: Seven studies met the inclusion criteria, encompassing 470 patients, of whom 311 had lipedema. The mean age was 47.4 years, and all patients were women. The mean body mass index was 32.6 kg/m2. Lymphoscintigraphy findings were normal in 61.4% of patients with lipedema. Tortuous lymph vessels were the most common abnormality (56.8%), followed by collateral lymph vessels (49.1%) and popliteal node visualization (44.0%). Dermal backflow (3.8%) and secondary lymphedema (11.8%) were less frequent. CONCLUSIONS: Lymphoscintigraphic alterations in patients with lipedema seem to reflect lymphatic overload rather than frank insufficiency. However, significant heterogeneity in study methodologies precluded a quantitative meta-analysis. Future research should focus on establishing standardized, consensus-based imaging protocols to better define the role of lymphoscintigraphy in the diagnosis and staging of lipedema.

A progressive disease, lipedema is characterized by bilaterally symmetrical and disproportional accumulation of subcutaneous adipose tissue (SAT) in the extremities, leading to severe pain, inflammation, and mobility issues. Lipedema predominantly affects women in all stages of life and treatment options are currently limited as patients' conditions can only be improved to a limited extent by diet or exercise. The pathogenesis of lipedema remains poorly understood and a reliable diagnostic marker is currently missing. Disease progression is marked by stage-dependent morphological adipose tissue changes, such as adipocyte hypertrophy and stage-dependent fibrosis, accompanied by an elevated proportion of anti-inflammatory macrophages. The molecular mechanisms regulating these compositional and structural changes in adipose tissue, and to what extent this altered response is cause or consequence of the disease, remain unclear. Therefore, the analysis of disease-related changes, with a focus on the cellular dynamics and tissue composition changes may help to distinguish lipedema more reliably from adiposity-related comorbidities.

Introduction: Lipedema is a chronic adipose tissue disorder characterized by disproportionate accumulation of subcutaneous fat, primarily affecting the lower extremities. The condition occurs almost exclusively in women and is associated with pain, tissue sensitivity, easy bruising, and progressive functional limitations. These symptoms can impair mobility and negatively affect quality of life.

Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with central pain syndromes, weak correlation between structural disease severity and pain intensity, and symptom clustering during reproductive transitions such as puberty, pregnancy, and menopause. Methods: This study aims to synthesize clinical, molecular, neuroimmune, and endocrine evidence on the interrelationship between endometriosis and lipedema, and to propose a hypothesis-generating neuroimmune framework linking both conditions. This integrative narrative review conducted a non-systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science, focusing on mechanisms related to chronic pain, mast cell biology, TRPV1 signaling, CGRP-mediated neurogenic inflammation, intracrine steroidogenesis, and peripheral and central sensitization. Results: The review identifies convergent biological characteristics between the two diseases, including mast cell activation, macrophage polarization, endothelial dysfunction, fibrosis, angiogenesis, intracrine estrogen metabolism, and persistent inflammatory signaling. In endometriosis, direct evidence demonstrates increased sensory innervation, nerve growth factor expression, TRPV1 sensitization, CGRP-positive fibers, and mast cell-nerve interactions. In lipedema, convergent upstream mechanisms, including mast cell infiltration, elevated histamine levels, adipose tissue inflammation, and local estrogen activation, support the plausibility of a functionally analogous neuroimmune organization, despite incomplete direct neural characterization. In this context, the mast cell-TRPV1-CGRP axis is proposed as a biologically plausible framework, directly supported in endometriosis and currently hypothetical in lipedema, connecting peripheral sensitization, neurogenic inflammation, hormonal chronodependence, and central nociceptive amplification. The model further conceptualizes pain crises as transient events of instability within a sensitized neuroimmune network and proposes mechanistic phenotypes that integrate gastrointestinal, inflammatory, central, and hormonal triggers. Conclusion: Endometriosis and lipedema may represent topographically distinct manifestations of a shared neuroimmune process operating within hormone-sensitive tissues. Although the evidentiary basis remains asymmetric, with stronger mechanistic support in endometriosis than in lipedema, this framework provides a biologically plausible and experimentally testable model integrating endocrine, immune, neural, and vascular contributors to chronic pain amplification. This perspective supports coordinated translational investigation across reproductive biology, endocrinology, and pain medicine and may contribute to future mechanism-based stratification and therapeutic development. This work is hypothesis-generating and is not intended to establish causality or to provide clinical recommendations; all proposed mechanistic and therapeutic inferences require prospective experimental validation.

ObjectivesGenerative artificial intelligence (AI) models capable of producing photorealistic medical images are increasingly proposed for patient education, clinical illustration, and trainee instruction. However, their ability to accurately represent anatomically distinct disease subtypes remains unclear. This study evaluated the diagnostic accuracy of a widely used generative AI model in producing images corresponding to the five anatomical lipedema types defined by the Schmeller classification.MethodsIn this prospective audit, ChatGPT’s image-generation interface was prompted to create 60 images for each lipedema type (Types I–V),yielding 300 images. Prompts were standardized and limited to the subtype label without additional descriptors. Two clinicians independently classified each image into one of the five lipedema types or as indeterminate, blinded to the original prompt; disagreements were resolved by a third clinician. Diagnostic performance was assessed using a confusion matrix and per-type sensitivity, specificity, positive predictive value(PPV), negative predictive value (NPV),F1-score,and one-vs-rest receiver operating characteristic area under the curve (ROC AUC). Overall accuracy and Cohen’s κ statistics were also calculated.ResultsAll 300 images were evaluable. The model generated anatomically consistent images for Types I,II, and III (sensitivity = 1.00 for each). Specificity was 1.00 for Types I and II but 0.50 for Type III because all images requested as Types IV and V were classified as Type III. Consequently, the model failed to generate any images consistent with Type IV(arm-predominant) or Type V(calf-isolated) lipedema (sensitivity = 0.00 for both). Overall accuracy was 0.600. Unweighted and quadratic-weighted Cohen’s κ values were 0.500 and 0.667, respectively. Micro- and macro-averaged ROC AUC were both 0.750.ConclusionThe model reproduces severity gradients within lower-extremity lipedema but systematically collapses anatomically distinct subtypes into the dominant Type III phenotype, failing to depict arm-predominant and calf-isolated disease. Current generative AI systems may therefore encode lipedema as a single visual phenotype rather than a distributed anatomical entity, limiting their reliability for medical education and clinical communication.

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: Lipedema is a chronic disorder that predominantly affects women and is characterized by abnormal subcutaneous adipose tissue accumulation, pain, and vascular dysfunction. However, reliable circulating biomarkers that reflect disease-specific pathophysiology are still lacking. This study investigated serum markers associated with adipose tissue, inflammation, and angiogenesis to further elucidate the pathophysiology of lipedema. Methods: In this cross-sectional observational study, fasting serum levels of adiponectin, chemerin, lipopolysaccharide-binding protein (LBP), proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble CD163 (sCD163), and soluble CD137 (sCD137)—proteins associated with obesity and inflammation—were measured in 23 premenopausal women with lipedema and 23 age-matched healthy premenopausal controls. Serum endostatin levels, an angiogenesis inhibitor, and insulin-like growth factor binding protein 2 (IGFBP2), a potent proangiogenic factor, were also assessed. Results: Patients with lipedema and obese controls had comparable body mass index, glucose, and serum lipid profiles. No significant differences were observed between groups in circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 and IGFBP2. In contrast, serum endostatin levels were significantly reduced in patients with lipedema (p = 0.038). Additional analyses demonstrated markedly higher endostatin expression in human subcutaneous adipose tissue than in the liver, suggesting that circulating endostatin levels may be related to adipose tissue mass. However, serum endostatin levels were lower in obese compared with normal-weight women (p < 0.001). Conclusion: Lipedema was not associated with altered circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 or IGFBP2. Reduced serum endostatin levels support a potential role for vascular dysfunction in the pathophysiology of lipedema.

Lipedema is a chronic disorder of subcutaneous adipose tissue characterized by disproportionate fat accumulation, pain, and progressive functional impairment, predominantly affecting women. Research remains fragmented across vascular, hormonal, metabolic, and gynecologic perspectives. Recent contributions have advanced specific axes: an international Delphi consensus, a systematic review of hormonal hypotheses, a stromal-vulnerability narrative, and a focused review of adipose biology; but no prior framework has integrated these domains into a single architecture annotated by level of evidence and capable of generating stratified, falsifiable research hypotheses. Here, we propose a hypothesis-generating translational framework that conceptualizes lipedema as the predominant adipose expression of a hormone-sensitive stromal vulnerability. The framework adds a specific molecular convergence axis, ERα/ERβ signaling imbalance interacting with intracrine steroid metabolism (aromatase, 17β-HSDs, AKR1C1), and resolves the disorder into four interacting biological pathways: (i) hormonal transition sensitivity across the female life course; (ii) metabolic– behavioral amplification; (iii) gynecologic–endocrine comorbidity; and (iv) intrinsic stromal–adipose susceptibility. The framework predicts that lipedema and its cognate expressions in hormone-responsive tissues (including gynecologic disease, connective tissue laxity, microvascular dysfunction, neurosensory amplification, and neuropsychological burden) may share a common stromal-endocrine substrate while preserving phenotypic specificity through dominant-pathway combinations. Four features distinguish this framework from prior syntheses: (a) ERα/ERβ signaling imbalance is articulated as a candidate molecular convergence axis linking adipose, gynecologic, connective-tissue, microvascular, and neuro-immune manifestations; (b) intracrine steroid metabolism (aromatase, 17β-HSDs, AKR1C1) is incorporated as the mechanistic anchor of stromal hormone-responsiveness; (c) per-component evidence-level annotation is applied throughout (Level 1A/1B: direct evidence in lipedema; Level 2: observational association; Level 3: mechanistic extrapolation); and (d) stratified, falsifiable research hypotheses are derived from dominant-pathway phenotypes. Two domains, metabolic burden and steroid signaling, emerge as promising translational research domains. Important limitations apply. Direct mechanistic evidence in lipedema-specific tissues is limited; much of the supporting biology is extrapolated from adipose, gynecologic, and metabolic literatures; and most clinical data derive from observational cohorts in referral centers. This article therefore proposes a hypothesis-generating translational framework, not a clinical guideline or therapeutic recommendation.

Lipedema is a chronic and underrecognized adipose tissue disorder in women, often misdiagnosed as obesity or lymphedema. Diagnosis is challenging due to overlapping clinical features and the lack of standardized imaging criteria. We report a 50-year-old postmenopausal woman, known hypothyroid on thyroxine and currently euthyroid, presenting with a 6-year history of progressive, symmetrical bilateral lower-limb swelling, predominantly involving the thighs and legs with sparing the feet. Body mass index was 37.8 kg/m2 (Class II obesity). Lower-limb Doppler ultrasonography excluded arterial or venous obstruction, and filarial serology was negative. Crucially, lymphoscintigraphy, a cost-effective and readily available nuclear medicine tool, demonstrated normal lymphatic drainage, excluding lymphedema and prompting whole-body dual-energy X-ray absorptiometry (DEXA) for further assessment. Whole-body DEXA revealed obesity with disproportionately increased and symmetrical lower limb fat, elevated fat mass index (16.7 kg/m2), and near-equal trunk-to-leg fat distribution, suggestive of a possible lipedema phenotype (Stage II). Magnetic resonance imaging showed extensive symmetrical fat signal intensity in the subcutaneous layer, supporting the DEXA findings. This case emphasizes the sequential role of nuclear medicine techniques—lymphoscintigraphy for functional lymphatic assessment and DEXA for quantitative body composition analysis—in the accurate diagnosis of lipedema, in an obese postmenopausal woman.

Background:Lipedema is a chronic connective tissue disorder characterized by painful subcutaneous adipose accumulation, mainly in the lower extremities. Pain is a hallmark feature, yet its mechanisms remain poorly defined. Neuropathic components may contribute, but direct comparisons with lymphedema are scarce.Methods:In this exploratory cross-sectional study, 118 female patients with lipedema (n = 62) or bilateral lower extremity lymphedema (n = 56) were assessed. Pain intensity was measured with the Visual Analogue Scale (VAS). Neuropathic pain was evaluated with painDETECT and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). Psychological status was measured using the Hospital Anxiety and Depression Scale (HADS), cognitive–emotional aspects with the Pain Catastrophizing Scale (PCS), and health-related quality of life with the WHOQOL-BREF.Results:Lipedema patients reported higher pain severity (VAS 6.2 ± 1.4 vs. 5.5 ± 1.5, p = 0.02) and greater neuropathic pain prevalence (42% vs. 21%, p < 0.01) than lymphedema. painDETECT and LANSS scores were significantly higher in lipedema (p < 0.001). HADS-Anxiety (10.2 ± 3.8 vs. 7.8 ± 3.5, p = 0.005) and PCS scores (29.5 ± 7.2 vs. 25.4 ± 6.5, p = 0.03) were also elevated, while HADS-Depression was slightly higher in lymphedema without significance. WHOQOL-BREF scores were similarly reduced in both groups compared to population norms. Correlation analyses showed strong associations between pain intensity, neuropathic features, catastrophizing, and anxiety, particularly in lipedema.Conclusions:A substantial proportion of lipedema patients exhibit neuropathic pain features and higher pain severity compared with lymphedema, while anxiety and pain catastrophizing appear to amplify symptom burden; however, quality-of-life impairment is substantial in both conditions, and the findings should be interpreted as hypothesis-generating with implications for more individualized management approaches.

Lipedema is a chronic adipose tissue disorder characterized by disproportionate and often painful enlargement of the extremities, occurring predominantly in women. Despite increasing clinical recognition, the underlying pathophysiology remains incompletely understood and is likely multifactorial. Existing evidence suggests contributions from vascular alterations, adipose tissue remodeling, inflammatory activation, hormonal influences, and lymphatic dysfunction. This review proposes a hypothesis-generating integrative framework in which lipedema may reflect a regenerative imbalance of subcutaneous adipose tissue. Within this model, genetically and hormonally modulated endothelial permeability could promote activation of perivascular adipose-derived stromal/stem-cell niches and stromal vascular fraction signaling pathways, thereby facilitating coupled angiogenesis and adipogenesis. Progressive adipocyte hyperplasia and hypertrophy may subsequently contribute to inflammatory remodeling, pain generation, and secondary impairment of dermal and subdermal lymphatic drainage. The proposed framework attempts to integrate clinical, histological, imaging, molecular, and endocrine observations into a biologically coherent conceptual model. At the same time, the review emphasizes the current limitations of the available evidence, the heterogeneity of lipedema phenotypes, and the ongoing controversies regarding disease progression, obesity overlap, and the relative role of lymphatic dysfunction. Finally, the potential mechanistic rationale of lymphatic-sparing liposuction is discussed in the context of tissue decompression, restoration of lymphatic transport, and interruption of persistent adipose remodeling. The model presented here should be interpreted as a hypothesis-generating conceptual scaffold requiring prospective validation. Importantly, the present framework should be interpreted as a biologically plausible and hypothesis-generating conceptual model rather than a definitive mechanistic doctrine. Several proposed interactions remain associative and require prospective biological validation.