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BACKGROUND: Despite an increased interest in visualising the lymphatic vessels (lymphatics) with Magnetic Resonance Lymphangiography (MRL), there remains little literature describing their appearance in non-lymphoedematous individuals. To determine lymphatic abnormalities, an understanding of how healthy lymphatics appear and behave needs to be established. In this study, MRL of individuals without a history of lymphatic disease was therefore performed. METHODS: A total of 25 individuals (15 female) underwent MRL of their lower limbs using a 3.0T Philips MRI scanner. The first 9 cases were recruited to establish the concentration of Gadolinium-based contrast agent (GBCA) to administer, with the remainder imaged pre- and post-inter-digital forefoot GBCA injections at the optimised dose. Outcomes including lymphatic vessel diameter, tortuosity and the frequency of drainage via particular drainage routes were recorded. RESULTS: Healthy lymphatics following the anteromedial pathway were routinely observed in post-contrast T1 weighted images (average tortuosity = 1.09 ±0.03), with an average of 2.16 ± 0.93 lymphatic vessels, of diameter 2.47 ± 0.50 mm, crossing the anterior ankle. In six limbs, vessels following the anterolateral pathways were observed. No vessels traversing the posterior of the legs were seen. In a subset of ten vessels lymphatic signal, measured at the ankle, peaked 29:50 ± 09:29 mm:ss after GBCA administration. No lymphatic vessels were observed in T2 weighted images. CONCLUSIONS: Contrast-enhanced MRL reliably depicts the lymphatics in the legs of healthy controls. Following inter-digital contrast injection, anteromedial drainage appears dominant. Quantitative measures related to lymphatic vessel size, tortuosity and drainage rate are readily obtainable, and could be beneficial for detecting even subtle lymphatic impairment.

Breast cancer-related lymphedema is currently one of the most serious complications that most affect the quality of life of women undergoing breast cancer. The aim of this study was to explore in-depth the experience of women who suffer from lymphoedema after breast cancer and how does this condition affect corporeality, with no judgements. For this purpose, a qualitative methodology was followed. In-depth interviews, interviewer's field notes and participants' letters were used for data collection. The participants were twenty Spanish women with lymphoedema after overcome a breast cancer in the past. Healthcare specialists with experience in the topic were also included. Results showed 2 main categories: "From cancer to lymphedema, another disease another disease" and "Potential for transition and transformation towards a new way of life". As a conclusion, the difficulty in accessing adequate treatment, the need for greater awareness of lymphedema and the importance of the emotional and psychological dimension of this chronic disease. Highlighting the attitudes that these women develop for self-care and the concept of new corporeality. After breast cancer, women with lymphedema experience a drastic change that affects all areas of their lives. The adaptation process, and the search for resources and aid, play a fundamental role in overcoming this process.

Body mass index (BMI) is seen as a predictor of cardiovascular disease (CVD) in lipedema patients. A valid predictor of CVD is increased aortic stiffness (IAS), and previous research described IAS in lipedema. However, it is not known if this applies to all patients. In this cross-sectional single-center cohort study, peripheral pulse wave velocity (PWV) as a non-invasive indicator of aortic stiffness was measured in 41 patients with lipedema, irrespective of stage and without pre-existing cardiovascular conditions or a history of smoking and a maximum body mass index (BMI) of 35 kg/m2. Automatically electrocardiogram-triggered oscillometric sensor technology by the Gesenius-Keller method was used. Regardless of the stage of lipedema disease, there was no significant difference in PWV compared to published standard values adjusted to age and blood pressure. BMI alone is not a predictor of cardiovascular risk in lipedema patients. Measuring other anthropometric factors, such as the waist-hip ratio or waist-height ratio, should be included, and the existing cardiovascular risk factors, comorbidities, and adipose tissue distribution for accurate risk stratification should be taken into account. Automated sensor technology recording the PWV represents a valid and reliable method for health monitoring and early detection of cardiovascular risks.

Lipedema, a chronic and painful disorder primarily affecting women without a definitive cure, has traditionally been managed with conservative therapy, notably complete decongestive therapy, across many countries. Recently, liposuction has been explored as a potential surgical treatment, prompting this study to evaluate its effectiveness as possibly the first-line therapy for lipedema. Through extensive literature searches in databases such as CrossRef, Web of Science, PubMed, and Google Scholar up to December 2023, and using the Newcastle-Ottawa Scale for quality assessment, the study selected seven studies for inclusion. Results showed significant post-operative improvements in spontaneous pain, edema, bruising, mobility, and quality of life among lipedema patients undergoing liposuction. However, over half of the patients still required conservative therapy after surgery. Despite these promising results, the study suggests caution due to lipedema's complexity, significant reliance on self-reported data, and limitations of the studies reviewed. Thus, while liposuction may offer symptomatic relief, it should be considered an adjunct, experimental therapy rather than a definitive cure, emphasizing the need for a comprehensive approach to care.

Background: Complex decongestive therapy (CDT) is the standard and basic therapy for lymphedema. The central component of CDT is manual lymphatic drainage (MLD). In addition to CDT, other measures such as intermittent pneumatic compression therapy (IPCT) (active compression machine therapy) are available. In this prospective research study, the objective and subjective effects of MLD and IPCT on lymphedema of the lower extremity were investigated and both therapies were directly compared. Furthermore, the patients' body mass index (BMI) and stage of lymphedema were tested for their effect on the respective therapy. Methods: Patients participating in the study received both therapies (MLD and IPCT) on the same lymphedema-affected limb at an interval of two days. The objective volumetric therapy effect was measured by the digital volume measurement of the affected limb. The subjective effects of the therapies were measured using two specially designed questionnaires. Results: A total of 40 patients were included in the study. There was no significant difference in the volume differences between the interventions, BMI categories, lymphedema, or treatment order regarding the immediate and two-day effect. Conclusions: No significant difference was found in the subjective or objective therapy efficacy of the two methods. Intermittent pneumatic compression therapy is considered a comparable therapeutic procedure when properly indicated.

We conducted a comparative study involving 39 female patients with lipedema and group-matched controls at a ratio of 1:5. The primary survey tool was the German Health Update (GEDA 2019/2020-EHIS) questionnaire, which was developed by the Robert Koch Institute (RKI), Germany. The secondary survey tool was the German Pain Questionnaire. The prevalence of hypertension (p = 0.041) and high blood lipids (p = 0.024) was lower in the lipedema group compared to the control group. General health and well-being indicators demonstrated lower overall health ratings (p < 0.001) and higher physiotherapy use in patients with lipedema (p = 0.016). Mental health assessment revealed higher depression prevalence and severity (p = 0.001), together with a lower number of close contacts (p = 0.032). Furthermore, patients with lipedema experienced higher levels of pain (p < 0.001) and more significant pain-related disability in daily activities (p < 0.001) than controls. Correlation analysis among patients with lipedema showed a positive correlation between pain severity and depressive symptoms (ρ = 0.612, p < 0.001) and a moderate positive correlation with impaired health-related quality of life (ρ = 0.418, p = 0.010). In summary, our findings highlight significant differences in health and well-being between patients with lipedema and matched controls, especially in overall, metabolic, and mental health, as well as pain perception. The findings emphasize the need for a validated lipedema-specific questionnaire and a multidisciplinary treatment approach with a combination of physical therapies, lifestyle adjustments, and psychological strategies.

BACKGROUND: Lipedema is characterized by the painful abnormal deposition of adipose tissue in the lower limbs and is often misdiagnosed as obesity. Considering the numerous bothersome physical symptoms of lipedema, women with lipedema may have greater disability and emotional problems than women with lifestyle-induced obesity. OBJECTIVES: Our study aims to assess disability, anxiety and depression symptoms in women with lipedema compared to women with overweight/obesity. MATERIAL AND METHODS: Women with lipedema (n = 45, with a mean age of 41 years) and women who are overweight/obese (n = 43, with a mean age of 44.95 years) were asked to complete the following questionnaires: The World Health Organization Disability Assessment Schedule (WHO-DAS II), Beck's Depression Inventory - II (BDI-II), and The Hospital Anxiety and Depression Scale (HADS). RESULTS: Despite the higher BMI in the overweight/obesity group, the group with lipedema was more disabled in numerous domains of the WHO-DAS II questionnaire, including Life activities - domestic, work and school responsibilities and Participation in society When the influence of BMI was adjusted, a difference in the domain of Mobility was also present. The study groups did not differ in anxiety and depression symptoms. CONCLUSIONS: We showed that behavioral impairment was the main factor affecting functioning in women with lipedema. Emotional symptoms did not differentiate the study groups. Leg volumes and adipose tissue pain intensity were associated with greater disability in women with lipedema, and should be considered in managing women with this condition and in future research estimating the effectiveness of lipedema treatment.

We analyzed the medical condition of 360 women affected by lipedema of the lower limbs in stages 1, 2, and 3. The data were assessed for the whole population and compared between different clinical stages, distinguishing between obese and non-obese patients. The most frequent clinical signs were pain when pinching the skin, subcutaneous nodules, and patellar fat pads. The most frequently painful site of the lower limbs was the medial lower third of the thigh. The pain score obtained on lower limb points increased progressively with the clinical stage. In all points evaluated, the thickness of the subcutaneous tissue increased with the clinical stage. Analyzing the data on the lower medial third of the leg and considering only patients with type 3 lipedema, the difference between stages was statistically significant after correction for age and BMI. We found higher levels of C-reactive protein at more severe clinical stages, and the difference was significant after correction for age and BMI between the stages. Overall, the prevalence of alterations of glucose metabolism was 34%, with a progressive increase in prevalence with the clinical stage. The most frequent comorbidities were vitamin D insufficiency, chronic venous disease, allergies, dyslipidemia, headache, and depression of mood. Interestingly, in comparison with the general population, we found higher prevalence of chronic autoimmune thyroiditis and polycystic ovary syndrome. Finally, the clinical stage and the involvement of the upper limbs or obesity suggest a worse clinical, anthropometric, and endocrine–metabolic profile.

Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema's underlying mechanisms.

Introdução: O lipedema, recentemente introduzido na 11ª revisão da Classificação Internacional de Doenças. Estima-se que metade das pessoas acometidas pelo lipedema, estejam em sobrepeso ou com obesidade, sendo uma associação de comorbidades que dificulta o diagnóstico. O diagnóstico errôneo é preocupante, pois atrasa o tratamento da doença permitindo a sua progressão. Objetivo: Trata-se de uma revisão integrativa da literatura (RIL) com objetivo de analisar o que se tem construído em pesquisas anteriores relacionadas ao lipedema. Metodologia: A busca dos artigos científicos foram os disponibilizados nos Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Os artigos constassem os Descritores em Ciências da Saúde (DeCS) com as palavras: lipedema and procedimento and cirurgia and mulher, e que fossem revisados por pares, nas línguas inglesa e portuguesa. a partir da aplicação dos critérios previamente definidos O período de busca foi realizado nos meses de maio a agosto de 2023. Resultados e Discussão: Foram elegíveis 12 artigos. A análise dos artigos encontrados possibilitou a evidente necessidade de conhecimento e clareza no diagnóstico do lipedema. As mulheres são as mais afetadas pela doença. A área afetada pode incluir os quadris, as pernas bilateral e simetricamente. E uma das principais características distintivas do lipedema é a preservação dos pés, o que pode criar um degrau distinto no tornozelo. Assim, a importância do diagnóstico diferencial. O procedimento cirúrgico como tratamento apresentou melhores resultados. Entretanto, a associação de todos os tratamentos sobressaiu na qualidade de melhora dos aspectos do lipedema. Conclusão: Essa revisão apontou para o complexo&nbsp; diagnóstico do lipedema.&nbsp; Esse assunto persiste como um desafio e deve instigar mais pesquisadores na busca para um diagnóstico preciso, opções de tratamento e até mesmo no sentido de prevenção para satisfazer a população assistida, no caso a maioria são as mulheres.&nbsp; A melhor opção indicada pelos estudos analisados foi o tratamento cirúrgico realizado pela lipoaspiração.

OBJECTIVE: Lipedema is a debilitating chronic condition predominantly affecting women, characterized by the abnormal accumulation of fat in a symmetrical, bilateral pattern in the extremities, often coinciding with hormonal imbalances. PATIENTS AND METHODS: Despite the conjectured role of sex hormones in its etiology, a definitive link has remained elusive. This study explores the case of a patient possessing a mutation deletion within the C-terminal region of Aldo-keto reductases Member C2 (AKR1C2), Ser320PheTer2, that could lead to heightened enzyme activity. A cohort of 19 additional lipedema patients and 2 additional affected family members14 were enrolled in this study. The two additional affected family members are relatives of the patient with the AKR1C1 L213Q variant, which is included in the 19 cohorts and described in literature. RESULTS: Our investigation revealed that AKR1C2 was overexpressed, as quantified by qPCR, in 5 out of 21 (24%) lipedema patients who did not possess mutations in the AKR1C2 gene. Collectively, these findings implicate AKR1C2 in the pathogenesis of lipedema, substantiating its causative role. CONCLUSIONS: This study demonstrates that the activating mutation in the enzyme or its overexpression is a causative factor in the development of lipedema. Further exploration and replication in diverse populations will bolster our understanding of this significant connection.

BACKGROUND: Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic investigations have uncovered potential contributors to its pathogenesis, including somatic mutations, which are nonheritable genetic alterations that can play a pivotal role in the development of this disease. AIM: This review aims to elucidate the role of somatic mutations in the etiology of lipedema by examining their implications in adipose tissue biology, inflammation, and metabolic dysfunction. RESULTS: Studies focusing on leukocyte clones, genetic alterations like TET2 and DNMT3A, and the intricate interplay between adipose tissue and other organs have shed light on the underlying mechanisms driving lipedema. From the study of the scientific literature, mutations to genes correlated to three main pathways could be involved in the somatic development of lipedema: genes related to mitochondrial activity, genes related to localized disorders of subcutaneous adipose tissue, and genes of leukocyte clones. CONCLUSIONS: The insights gained from these diverse studies converge to highlight the complex genetic underpinnings of lipedema and offer potential avenues for therapeutic interventions targeting somatic mutations to alleviate the burden of this condition on affected individuals.

BACKGROUND: Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema. OBJECTIVE: Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema. METHODS: Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks. RESULTS: Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity. CONCLUSION: Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.

This study aimed to assess the potential benefits of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to overweight or women with obesity. The study included 113 female participants, 56 with lipedema and 57 with overweight/obesity (BMI >25 kg/m2) without lipedema. All subjects were prescribed a low-carbohydrate, high-fat (LCHF) diet with anti-inflammatory properties to adhere to for a duration of 7 months. Measurements of anthropometry, body weight, composition, and pain (VAS) were conducted at the study’s commencement and conclusion. 52 participants completed the study. Both groups experienced a similar weight reduction, amounting to 12.9% compared to the baseline (−10.8 kg vs. −11.9 kg; p = 0.14, for lipedema and women with overweight/obesity, respectively). The most reduction was in body fat mass. Improvements in various parameters were observed, except for ankle circumferences, which decreased more in the lipedema group. Lipedema participants showed significantly reduced pain levels following the LCHF diet (4.6 ± 2.6 vs 3.0 ± 2.3; ). The LCHF diet holds promise for weight loss, body fat reduction, leg volume management, and pain alleviation in women with lipedema. These findings provide valuable insights into potential therapeutic strategies for lipedema management.

PURPOSE OF REVIEW: This review aims to provide an overview of the current evidence on the efficacy, also considering the anti-inflammatory properties and safety of very low-calorie ketogenic diet (VLCKD) as a potential treatment for lipedema, particularly in the context of obesity. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal and painful fat buildup on the legs and/or arms. It is often misdiagnosed as obesity or lymphedema. However, although lipedema and obesity can coexist, unlike obesity, lipedema usually affects the legs and thighs without affecting the feet or hands, and the abnormal deposition of adipose tissue in lipedema is painful. The current lifestyle interventions are often unsuccessful in the management of lipedema. There is no consensus on the most effective nutritional approach for managing lipedema. Recent studies have suggested that VLCKD may be an effective treatment for lipedema, demonstrating that it is also superior to other nutritional approaches such as Mediterranean diet or intermittent fasting. Lipedema is a chronic and debilitating disease characterized by abnormal and painful accumulation of adipose tissue in the legs. VLCKD has been shown to be an effective treatment for lipedema, especially in the context of obesity, due to its anti-inflammatory properties. However, further research is needed to determine the long-term safety and efficacy of VLCKD as a treatment for lipedema.

BACKGROUND: Lipedema is a chronic inflammatory subcutaneous adipose-rich connective tissue disease affecting millions of women worldwide. Disproportionate fat accumulation on the extremities characterized by heaviness, tenderness, and swelling can affect function, mobility, and quality of life. Treatments include conservative measures and lipedema reduction surgery (LRS). Here, we report lipedema comorbidities and surgical techniques, outcomes measures, and complications after LRS. METHODS: This is a single outpatient clinic retrospective chart review case series of comorbidities and complications in 189 women with lipedema. Bioelectrical impedance analyses, knee kinematics, gait, physical examinations, Patient-Reported Outcomes Measurement Information System, and RAND Short Form-36 questionnaires collected before and after LRS were analyzed for 66 of the 189 women. Hemoglobin levels were measured by transdermal hemoglobin monitor (Masimo noninvasive hemoglobin monitoring; Irvine, Calif.). RESULTS: Common comorbidities in 189 women were hypermobile joints (50.5%), spider/varicose veins (48.6/24.5%), arthritis (29.1%), and hypothyroidism (25.9%). The most common complication in 5.5% of these women after LRS was lightheadedness with a 2-g reduction or more in hemoglobin. After conservative measures and LRS in 66 women, significant improvements (P ≤ 0.0009) were found for: (1) knee flexion (10 degrees); (2) gait; (3) Patient-Reported Outcomes Measurement Information System T-score (16%); (4) mobility questions: gait velocity, rising from a chair, stair ascent; (5) RAND Short Form-36 scores: physical functioning, energy/fatigue, emotional well-being, social function, general health; (6) and Bioelectrical impedance analyses total and segmental body fat mass. CONCLUSION: LRS provided significant improvements to women with lipedema using direct physical measurements and validated outcome measures, comparable to those seen after total knee replacement.