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Obesity is increasingly recognized not only as a metabolic disorder, but also as a state of chronic low-grade inflammation that predisposes to systemic complications. Within this context, Dercum's disease (DD), or adiposis dolorosa, emerges as a rare yet debilitating disorder characterized by painful subcutaneous lipomas, most commonly affecting middle-aged women. Despite its clinical impact, DD remains underdiagnosed and is often misclassified as lipedema, fibromyalgia, or lipomatosis, complicating prevalence estimates and hindering the development of targeted interventions. Current evidence suggests that DD represents a distinctive model of inflammatory obesity, where adipose tissue actively contributes to pain generation rather than serving as a passive fat reservoir. Histological and molecular findings point to adipose tissue dysfunction, immune cell infiltration, and elevated secretion of pro-inflammatory adipokines, signals which appear to fuel systemic low-grade inflammation, perineural immune interactions, and nociceptor sensitization. Peripheral mechanisms further shape the clinical phenotype. While familial clustering suggests possible genetic contributions, no definitive markers have been identified, and the role of obesity-induced epigenetic modifications remains unexplored. Therapeutic strategies remain largely symptomatic, including analgesics, antidepressants, physical rehabilitation, and surgical excision of lipomas, whereas molecularly targeted and diet-based interventions are still experimental. This article discusses the pathophysiology of DD, current treatments, and future perspectives, emphasizing that advancing patient registries, omics-based analyses, and interdisciplinary clinical trials will be crucial to elucidate disease mechanisms and guide novel therapies. Improved understanding of DD may not only enhance patient care, but also provide broader insights into the interplay between obesity, inflammation, and chronic pain.

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular matrix fibrosis, mitochondrial dysfunction, and sex steroid imbalance, highlighting the need for disease-modifying therapies. This narrative review synthesizes mechanistic, translational, and clinical evidence linking metabolic, inflammatory, and fibrotic pathways to lipedema and tirzepatide's potential therapeutic relevance. Tirzepatide, a dual GLP-1 (Glucagon-Like Peptide-1)/GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor agonist, has demonstrated unprecedented efficacy in obesity and diabetes, alongside pleiotropic actions on inflammation, fibrosis, and adipose remodeling. Mechanistic studies reveal favorable effects on macrophage polarization, cytokine signaling, extracellular matrix turnover, and thermogenesis, suggesting potential relevance to lipedema biology. Translational evidence from related fibro-inflammatory conditions such as steatohepatitis and heart failure further supports its antifibrotic and immunomodulatory plausibility. Although direct clinical evidence in lipedema is lacking, the convergence of mechanistic pathways provides a strong rationale to investigate tirzepatide as a disease-modifying candidate. If future clinical studies confirm these mechanisms, tirzepatide could represent a novel metabolic-hormonal therapy capable of modifying the natural course of lipedema.

Background/Objectives: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation and inflammation, predominantly affecting women. While recent evidence suggests a systemic pro-inflammatory state in lipedema, the role of diet in modulating inflammation remains underexplored. This study assessed the anti-inflammatory potential of a Mediterranean-style ketogenic diet and its effects after 7 months of adherence on systemic inflammation markers (CRP and IL-6) in women with lipedema (n = 24) and a control group with overweight/obesity (n = 24). Methods: The Dietary Inflammatory Index (DII) was used to characterize the inflammatory potential of the diet throughout the intervention. Dietary intake was analyzed pre- and post-intervention, and anthropometric, body composition, and biochemical parameters were measured. Results: Beyond its beneficial effects on body composition (significant reductions in body weight, fat, leg circumferences, and visceral fat), the intervention diet also demonstrated anti-inflammatory potential. In lipedema, baseline diet showed a pro-inflammatory DII profile (DII/day = 3.04), which was reduced by about 1.5 points after the intervention (p = 0.008). When expressed per 1000 kcal, the DII values were markedly lower for both baseline (DII = 0.22) and intervention diet (DII = ~0.01). Following the intervention diet, reduction in CRP (-0.39, p = 0.016) and IL-6 levels (-0.33, p = 0.034) in lipedema were observed. A significant positive association was observed between the intervention diet's DII and CRP (r = 0.55, p = 0.005), and between the baseline diet's DII and IL-6 (r = 0.50, p = 0.013) in lipedema group. Conclusions: These findings suggest that ketogenic diet rich in anti-inflammatory and antioxidant nutrients can reduce systemic inflammation in lipedema patients, independently of caloric restriction.

BACKGROUND: Lipedema is a chronic disorder of adipose tissue that predominantly affects women and is frequently misdiagnosed as obesity or lymphedema. Traditionally associated with the lower extremities, lipedema can also involve the abdominal region, although there are currently no established diagnostic criteria for abdominal lipedema. This study aims to propose a diagnostic algorithm for abdominal lipedema based on clinical features, macroscopic observations, and ultrasound findings. METHODS: This retrospective study analyzed data from 327 patients treated between March 2018 and March 2024 for lipedema, including those with abdominal involvement. Clinical evaluations, ultrasound imaging, and surgical outcomes were examined to assess the prevalence and characteristics of abdominal lipedema. Patients were classified based on lipedema severity, and criteria for abdominal lipedema diagnosis were established through clinical and imaging data. RESULTS: The study identified that abdominal involvement increases with the severity of lipedema, with 31% of patients with stage II lipedema and 70% of those with stage III lipedema exhibiting abdominal manifestations. The proposed diagnostic algorithm includes maximum, major, and minor criteria, such as symmetrical fat deposition, pain, and non-responsiveness to diet and exercise. Specific threshold values for each category were defined to establish the diagnosis. The findings highlight the existence of both ascending (from legs to abdomen) and descending (from arms to abdomen) centripetal progression patterns, challenging traditional notions that limit lipedema to the extremities CONCLUSION: Abdominal lipedema is a significant and underrecognized manifestation of the condition, requiring specific diagnostic criteria to ensure accurate diagnosis and appropriate treatment. The study proposes a diagnostic framework based on clinical and imaging features that can improve the recognition and management of abdominal lipedema. Multidisciplinary treatment approaches, including both conservative measures and surgical interventions such as abdominoplasty and liposuction, are recommended to improve patient outcomes. 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 .

ObjectiveThe incidence of lipedema is poorly described due to its confusion with lymphedema. Patient education is crucial for treatment and prevention strategies but also for improving healthcare outcomes. This study assessed and compared the quality of English and Spanish online resources for patients suffering from lipedema using a multimetric approach.MethodsA deidentified Google search using the terms "lipedema" and "lipedema español" was conducted. The first 10 academic/organizational websites in each language were selected. Quality assessment was performed using the Patient Education and Materials Assessment Tool (PEMAT), Cultural Sensitivity Assessment Tool (CSAT), Simple Measure of Gobbledygook (SMOG), and facticity criteria to evaluate understandability and actionability, cultural sensitivity, readability, and factual quality, respectively.ResultsEnglish webpages scored 73.70% for understandability and 35.0% for actionability, while Spanish webpages scored 75.05% and 21.0%, respectively; no significant differences were found between languages in understandability (p = .970) and actionability (p = .895). A significantly higher proportion of Spanish resources was found to be culturally sensible than English resources (90% vs 70%; p < .001). However, no significant differences were found in the cultural sensitivity score (English 2.87 vs Spanish 3.01; p = .677). The grade reading level for Spanish materials was significantly lower compared to English materials (11.08 vs 13.45; p = .006). Factual quality was low across both languages according to the facticity framework, though English materials scored higher than Spanish (2.20 vs 1.00; p = .051).ConclusionOur results suggest that online English and Spanish materials on lipedema have inadequate actionability, facticity, and reading grade levels for patients. Nonetheless, the levels of understandability and cultural sensitivity are acceptable. Enhancing the quality of online health literature for lipedema patients presents an opportunity to alleviate psychosocial burdens and address misconceptions.

Lipoedema (lipalgia) is a condition that is often underdiagnosed or misdiagnosed as obesity or lymphoedema, which can result in mismanagement of treatment leading to poor mental and physical outcomes. It is a condition that is predominately seen in those assigned female at birth and rarely identified at an early age. Inconsistencies regarding criteria used for diagnosis and staging has led to challenges in the reliability of treatment options available for people with the condition. Poor diagnosis can substantially impact on a person's quality of life in terms of mental health, physical health and finances. Lipoedema has different stages and classifications according to visual characteristics. Recommended developments of practice include the setting up of a diagnostic criteria to identify key symptoms of lipoedema, which can help practitioners consider effective treatment options alongside diet, exercise, compression therapy and skin care as part of the overall treatment plan.

ObjectiveTo assess the relationship between disease severity in lipedema and tissue stiffness measured using shear wave elastography (SWE) concerning pain threshold and quality of life as well as determine differences in subcutaneous tissue stiffness between patients with lipedema and healthy subjects.Methods71 participants were subjected to measurements using subcutaneous tissue elastic modulus with SWE imaging of lower limbs at three anatomical levels. The participants were divided into two groups: those diagnosed with lipedema (Group (1) (n = 35) and healthy subjects (Group (2) (n = 36). Patients with lipedema were categorized into three stages based on disease severity. Pain levels were assessed using the visual analog scale (VAS), pain pressure threshold through algometric measurement within lipedema stages, and quality of life using EQ-5D quality of life scale in all groups.ResultsNo statistically significant differences in age, BMI, right and left three-zone elastic modulus averages were observed between the groups within BMI levels of 25-29.9 and ≥30 kg/m2 (p > .05). Same BMI group, according to lipedema stage, the mean elastic modulus of the right pretibial region in stage 2 cases was significantly higher than in stage 1 cases within BMI levels of 25-29.9 kg/m2 (p < .05). The all-region algometric measurements in Group 1 were significantly lower than those in Group 2, within BMI levels of 25-29.9 kg/m2 and ≥30 kg/m2. The average spontaneous VAS scores in Group 1 were significantly higher than those in Group 2 within the same BMI (p < .05). The VAS palpation scores in Group 1 exceeded those in Group 2 for BMI ≥30 kg/m2 (p < .05). No significant difference in VAS palpation scores was observed for BMI 25-29.9 kg/m2 (p > .05). The EQ-5D VAS scores of the control group were significantly lower than those of stage 1, 2, and 3 cases (p < .05).ConclusionsIn lipedema, pain characteristics may be more distinctive than the elastic properties of adipose tissue. Increased algometric measurements may reflect a specific objective sensation.

BackgroundTo evaluate kinesiophobia and its relationship with disease-related characteristics and quality of life in lipedema patients.MethodsIn this descriptive case-control study, 40 lipedema patients and 40 participants in the control group were included. All participants were evaluated in terms of body mass index (BMI), pain numeric rating scale (NRS) and pain threshold (PT) scores, kinesiophobia (Tampa Scale for Kinesiophobia - TSK), lower extremity functional scores (Lower Extremity Functional Scale - LEFS), and health-related quality of life (Nottingham Health Profile - NHP) scores. Additionally, the lipedema patients were evaluated in terms of extremity volumes, and total and mean lower extremity fat mass by dual-energy X-ray absorptiometry.ResultsHigh kinesiophobia was detected in 78% of the lipedema patients and 55% of the control group (p = .033). TSK (p = .048), NRS (p = .001), and NHP total scores (p = .041) were higher and PT scores (p = .007) were lower in lipedema patients compared to the control group. No difference was found between lipedema patients with high and low kinesiophobia in terms of fat mass or extremity volumes. A positive correlation was found between TSK score, NHP total score (r = 0.356, p = .024), NHP physical activity (ρ = 0.403, p = .010) and NHP energy (ρ = 0.436, p = .005) subscale scores.ConclusionKinesiophobia is highly prevalent in lipedema patients, regardless of disease-related data and affecting the quality of life of the patients, negatively.

BACKGROUND: Lipedema is an adipose tissue disorder involving mostly women. One of the most characteristic lipedema symptoms is painful accumulation of adipose tissue in lower and upper extremities leading to disproportion. Due to the disproportionate body shape, it is recently thought that BMI (Body Mass Index) might not be fully sufficient to identify the weight ratios among lipedema patients and it is suggested to consider replacing BMI with WHtR (Waist-to-height ratio). PURPOSE: The aim of the study is to present the characteristic features of lipedema patients and the usefulness of BMI and WHtR among lipedema patients in reference to symptoms severity, quality of life and body composition. METHODS: Forty-four women with lipedema were asked to rate their symptoms in a scale from 0 to 10, and to complete SF-36 questionnaire affecting quality of life. Participants also had body composition assessment. RESULTS: Participants experienced various lipedema symptoms such as: heaviness in affected areas (97.7%), pain at palpation (100%), spontaneous pain (82%), disproportionate body shape and tendency to bruising (88.6%). The level of pain was strictly correlated with patients' daily functioning (R = 0.79, p = 1.9*10- 10). The quality of life among participants measured with SF-36 was 57.4/100. WHtR enabled the same group of patients to be divided into three nearly equal groups, while BMI only divided them into two groups. Statistically significant differences could be observed both between BMI and WHtR groups. CONCLUSION: Lipedema symptoms have a direct impact on functioning of patients. Quality of life is decreased among women with lipedema. WHtR should be considered as a tool in identification of obesity among lipedema population.

BACKGROUND: Lipedema is a chronic, progressive and underdiagnosed condition characterized by bilateral, disproportionate and painful subcutaneous fat accumulation in extremities. Key symptoms include pain, heaviness and easy bruising. Surgical treatment, particularly liposuction, has shown excellent outcomes in symptom reduction and quality of life improvement. This study evaluates clinical outcomes in symptoms and aesthetic self-perception improvements in patients treated with selective combined liposuction (SCL). PATIENTS AND METHODS: A retrospective review of 126 female patients who underwent surgical treatment over a four-year period was performed. Selective tumescent liposuction combining power-assisted liposuction (PAL) with VASER (ultrasound-assisted liposuction) for proximal areas, especially the thighs. Demographic and clinical data, including BMI, medical history and comorbidities were analyzed. Symptoms such as pain, heaviness and edema, and body image perception were assessed preoperatively and six months postoperatively with a structured questionnaire. RESULTS: The mean patient age was 39 years, with a mean BMI of 27.2. The mean aspirated volume was 3270 mL per procedure. In 25.4% of the cases (n=32), a second procedure was required, with an average total aspirated volume of 5150 mL. Significant symptom improvement was observed: 89% reported reduced pain, 92% reduced heaviness, 82% reduced edema. Mobility limitations improved in 91% of patients, while 60% reported enhanced aesthetic perception of their extremities. Additionally, 68% of patients expanded their wardrobe postoperatively. CONCLUSIONS: Selective combined liposuction is a safe and highly effective technique for lipedema treatment, providing substantial symptom relief, improved body aesthetic self-perception, which leads to an improvement in the quality of life.

Lipoedema is a disease that affects women and is characterised by an abnormal accumulation of fatty tissue, with pain and a feeling of heaviness in the lower limbs. Approximately 30 % of patients also have involvement of the upper limbs. The cause of lipoedema is unknown, but familial clustering of the condition suggests an underlying genetic cause. Oestrogen and hormonal changes appear to be involved, as the condition occurs predominantly in women and is linked to hormonal fluctuations. In Norway, women with lipoedema have had limited access to treatment within the public health service, and the condition is relatively unknown among Norwegian healthcare personnel. Internationally, the diagnosis and treatment of lipoedema are largely based on consensus, as there is a lack of definitive scientific evidence in relation to pathophysiology and treatment. This clinical review presents lipoedema diagnostics and treatment based on clinical experience and international published consensus statements.

Adipose tissue, or “fat”, has become synonymous with obesity. The public discourse frames a desire to reduce or even banish this tissue at almost every turn, with reasons ranging from aesthetics to health improvements. During decades of research into the development of adipose tissue-reducing interventions, there has also been an increasing acknowledgement and understanding of the physiological necessity for adipose tissue. Functional adipose tissue contributes to overall health due to its role in an incredibly diverse array of processes. For that reason, dysfunction in this tissue continues to be linked to a wide variety of pathologies, from infection to cancer and everything in between. In this book, we gather expert input from those currently expanding this field to provide insight into the importance of adipose tissue.

INTRODUCTION: Lipedema is a chronic and progressive disease that predominantly affects women, characterized by a disproportionate increase in subcutaneous adipose tissue (AT), particularly in the lower limbs. It is associated with significant physical disability, chronic pain, thromboembolism, and psychosocial distress. Despite its profound impact on women's health and quality of life, lipedema remains underrecognized and insufficiently studied, with an estimated prevalence of approximately 10% among women worldwide. Although the exact etiology of lipedema remains unclear, emerging evidence suggests a multifactorial origin involving genetic predisposition, hormonal influences, and vascular dysfunction-all contributing to its development and progression. Current therapeutic options provide only partial symptom relief and remain noncurative, highlighting the urgent need for expanded research and improved management strategies. METHODS: A systematic review was conducted to assess the current understanding of lipedema pathophysiology and current treatment options. Research articles were sourced from PubMed, Web of Science, ScienceDirect, and Scopus databases. Over 100 studies were incorporated. RESULTS: This review provides a comprehensive overview of lipedema, encompassing its clinical features, pathophysiological mechanisms, diagnostic challenges, and current treatment modalities. Additionally, the review discusses whether the molecular and metabolic differences between abdominal and femoral AT depots mirror those observed in classical obesity. CONCLUSIONS: Multidisciplinary, research-informed care is essential for managing lipedema, combining conservative therapies, tailored exercise, and liposuction for advanced cases. More research to better understand the underlying pathophysiology is critical to developing targeted treatments, improving diagnostic accuracy, and informing standardized, evidence-based care.

Objectives: This study aimed to examine the effects of a multimodal exercise program on edema, pain, exercise capacity, lower extremity muscle strength, and function in patients with lipedema.Methods: The patients diagnosed with lipedema were randomly assigned to either the exercise (n: 11) or control (n: 11) groups. The exercise group participated in supervised group exercises focusing on aerobic and strengthening, twice a week for 6 weeks. The control group received training on physical activity additionally lipedema management. Sociodemographic and clinical characteristics were recorded. Edema (circumference measurements and local tissue water-LTW%), pain intensity (Visual Analogue Scale-VAS) and pressure pain threshold (Algometer), functional exercise capacity (Six minute walk test-6MWT), lower extremity muscle strength (Handheld dynamometer), lower extremity muscle strength/endurance (Sit-to-stand test) and lower extremity function (Lower Extremity Functional Scale-LEFS) were evaluated.Results: In the exercise group, significant reductions in pain during rest, activity, and nighttime, 6MWT distance, quadriceps and hip muscle strength, lower extremity strength/endurance, and function were observed (p < .05). When comparing the groups, no significant differences were found (p > .05); however, clinically, there were differences in limb volumes, pain reduction, muscle strength, and functional improvements, with medium to large effect sizes.Conclusion: The main findings of this study highlight the benefits of structured multimodal exercises for patients with lipedema to improve pain, limb volumes, exercise capacity, lower extremity muscle strength, endurance, and functionality.Clinical trials number: NCT06811961.

Lipedema is an adipose tissue disorder that principally affects women and is frequently misidentified as obesity or lymphedema. There have been relatively few studies that have precisely defined the pathogenesis, epidemiology, and treatment approaches for lipedema. However, successfully recognizing lipedema as a distinct condition is important for proper management. This review aimed to examine the existing literature on the epidemiology, pathogenesis, clinical presentation, differential diagnosis, and treatments for lipedema. The current research indicates that lipedema appears to be a clinical entity related to genetic factors and fat distribution, although distinct from lymphedema and obesity. Some available treatments include complex decongestive physiotherapy, liposuction, and laser-assisted lipolysis. The management of lipedema is complex and differs from that of lymphedema. Further high-quality randomized controlled trials are urgently needed to continue advancing our understanding of this often neglected disease and exploring optimal medical and surgical treatment regimens tailored specifically for lipedema patients. In summary, despite frequent misdiagnosis, enhanced recognition, and research into customized therapeutic strategies for this poorly characterized but likely underdiagnosed disorder represent promising steps forward. Level of evidence  N/A.

Background: Pain is a prevalent symptom in patients with lipedema predominantly impacting the lower extremities. This study aimed to evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] and vitamin B12 levels and neuropathic pain (NP) in patients diagnosed with lipedema. Methods and Results: A total of 243 patients with lipedema who had 25(OH)D and B12 levels measured in the past 6 months were included in this study. Participants were divided into two groups: Group 1 (N = 78) with NP scores ≥13 and Group 2 (N = 165) with NP scores <13. The Turkish version of the painDETECT questionnaire was used to assess the patients' NP symptoms. Pain levels were measured using the Visual Analog Scale (VAS) and pain threshold through algometric measurement. Group 1 had significantly higher palpation and spontaneous VAS scores, and pain threshold through algometric measurements than Group 2 (p < 0.05). No statistically significant difference was found between the groups regarding vitamin D levels being below 30 ng/mL or vitamin B12 levels being below 400 pg/mL (p > 0.05). Conclusions: No association was found between NP and 25(OH)D or B12 levels in patients with lipedema.