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Summary Lipedema is a painful, chronically progressive disease that is characterized by a symmetrical increase in subcutaneous fat with fluid accumulation on the legs and / or arms. Due to ignorance of the clinical picture, the disease is often not recognized or misinterpreted. Correct diagnosis and treatment are important, however, as the prognosis of the disease can be influenced. A causal therapy for lipedema is not known because the exact etiology is not yet fully understood. A hereditary component is suspected on the basis of a family history of the disease. Since lipedema occurs almost exclusively in women and the onset of the disease is often associated with the onset of hormonal changes (puberty, pregnancy, menopause), In addition, the estrogen is assigned a decisive role in the development. In the present work we present an overview of the symptoms and clinical features of lipedema, its differential diagnoses, treatment options and, lastly, the current hypotheses on the pathogenesis of lipedema.

IN JUNE 2020, the Lipedema ICD-10-CM Committee, with support from the American Vein & Lymphatic Society (AVLS), submitted an application to the US Centers for Disease Control and Prevention to establish new ICD-10-CM codes for lipedema and lipolymphedema, two related adipose tissue disorders. Currently,

Patients with obesity-associated lipoedema minimize by diet only the regular fat especially in the lower leg area. The pathological lipoedema with a possible secondary lymphodynamic oedema remains and causes skin irritation, discomfort and pain wearing the compression elements. The dorsal lower leg lift with previous liposuction is a useful therapeutic strategy to overcome these difficulties. A 37-year-old female patient after post-bariatric surgery and massive weight loss (MWL) presented with a lower leg lipoedema and lymphodynamic oedema. She underwent a liposuction removing lipoedema of the lower leg followed by a calf lift procedure on both sides. With sufficient surgical experience in skin tightening surgery after MWL, a significant improvement in day-to-day problems in patients with lipoedema can be achieved by dorsal lift of the lower leg after liposuction.

Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.

Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.

Lipedema is a painful fat disease of loose connective tissue usually misdiagnosed as lifestyle-induced obesity that affects ~10% of women of European descent as well as other populations. Lipedema is characterized by symmetric enlargement of the buttocks, hips, and legs due to increased loose connective tissue; arms are also affected in 80% of patients. Lipedema loose connective tissue is characterized by hypertrophic adipocytes, inflammatory cells, and dilated leaky blood and lymphatic vessels. Altered fluid flux through the tissue causes accumulation of fluid, protein, and other constituents in the interstitium resulting in recruitment of inflammatory cells, which in turn stimulates fibrosis and results in difficulty in weight loss. Inflammation and excess interstitial substance may also activate nerve fibers instigating the painful lipedema fat tissue. More research is needed to characterize lipedema loose connective tissue structure in depth, as well as the form and function of blood and lymphatic vessels. Understanding the pathophysiology of the disease will allow healthcare providers to diagnose the disease and develop treatments.

Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.

Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.

BACKGROUND: Adipose-derived Stem Cells (ASCs) present great potential for reconstructive procedures. Currently, isolation by enzyme digestion and culturing using xenogenic substances remain the gold standard, impairing clinical use. METHODS: Abdominal lipo-aspirate and blood samples were obtained from healthy patients. A novel mechanical isolation method for ASCs was compared to (the standard) collagenase digestion. ASCs are examined by flowcytometry and multilineage differentiation assays. Cell cultures were performed without xenogenic or toxic substances, using autologous plasma extracted from peripheral blood. After eGFP-transfection, an in vivo differentiation assay was performed. RESULTS: Mechanical isolation is more successful in isolating CD34+/CD31-/CD45-/CD13+/CD73+/CD146- ASCs from lipo-aspirate than isolation via collagenase digestion (p <0 .05). ASCs display multilineage differentiation potential in vitro. Autologous plasma is a valid additive for ASCs culturing. eGFP-ASCs, retrieved after 3 months in vivo, differentiated in adipocytes and endothelial cells. CONCLUSION: A practical method for human ASC isolation and culturing from abdominal lipo-aspirate, without the addition of xenogenic substances, is described. The mechanical protocol is more successful than the current gold standard protocol of enzyme digestion. These results are important in the translation of laboratory-based cell cultures to clinical reconstructive and aesthetic applications.

Background: Sonographic findings differ in patients with primary lipedema from those with lymphedema. This project was designed to quantify those differences and objectively characterize findings of lipedema and lymphedema in the lower extremity. Methods and Results: Patients with a clinical diagnosis of ISL stage I-II lipedema or lower extremity lymphedema that received ultrasound evaluation were included in this study. Thickness and echogenicity of the skin and subcutaneous fat layer were measured at the level of the ankle, calf, and thigh in each patient. The cohort analyzed included 12 patients with lipedema (12 lower extremities) and 10 patients with unilateral lymphedema (10 lower extremities with lymphedema and 8 lower extremities used as controls). Mean skin thickness of the ankle and calf was greatest in the lymphedema group compared to those with lipedema or controls (p < 0.01 and p < 0.01, respectively). The mean thickness of the subcutaneous fat layer of the thigh was greatest in those with lipedema (p < 0.01). Mean dermal to subcutaneous fat echogenicity ratio was decreased in those with lymphedema (ankle, 0.91; calf, 1.05; thigh, 1.19) compared to lipedema (ankle, 1.36; calf, 1.58; thigh, 1.54) and control (ankle, 1.26; calf, 1.54; thigh, 1.56) (p < 0.01, p < 0.01, and p = 0.02, respectively). Conclusions: Lymphedema appears to be associated with increased skin thickness and dermal hypoechogenicity, particularly in the distal lower extremity, compared to lipedema or controls. Conversely, lipedema may be associated with increased thickness and hypoechogenicity of the subcutaneous fat. Overall, these findings suggest that ultrasound may be an effective tool to differentiate these diseases and potentially guide treatment.

Syndromes with localized accumulation of subcutaneous fatty tissue belong to a group of genetically and phenotypically heterogeneous disorders. These diseases may show some common signs, such as nodular fat, symmetrical fat masses, obesity, fatigue, lymphedema and symmetrical lipomas (painful or otherwise). Other symptoms may be specific for the different clinical entities, enabling correct differential diagnosis. Disorders belonging to this spectrum are lipedema, generalized diffuse or nodular forms of Dercum disease, localized nodular Dercum disease and multiple symmetric lipomatosis. Here we summarize the genes involved in syndromes with localized accumulation of subcutaneous fat and the test we use for genetic analysis.

Lipoedema is a progressive disorder that is characterized by an abnormal distribution of subcutaneous adipose tissue, which results in a disproportion between the extremities and the trunk. This vascular/dermatological disease might have a detrimental impact on psychosocial wellbeing and quality of life. In this article, we report on a patient with morbid obesity that had a Roux en-Y Gastric bypass with sufficient weight loss. However, due to this weight loss, an abnormal disproportion came to light. A dermatologist diagnosed lipoedema five years after the surgery. Eventually, she had a dermolipectomy of the upper arms, of which reimbursement was initially rejected by her insurance.

640 patients from a specialist clinic for operative lymphology were surveyed with the help by a questionnaire issued by the German Society of Pain Therapy (Deutsche Schmerzgesellschaft e. V.). This survey collected responses to questions about pain and pain characteristics as well as demographic data. It revealed that only a little more than 50 % of respondents were genuine cases of obesity. Lipoedema and obesity must therefore be regarded as clinical pictures unrelated to one another. The pain was mostly described as pressing and tearing in nature. Attributes such as throbbing or pulsing, consistent with acute inflammation, were rated as "not applicable". Symptoms were independent of the BMI, which is only useable to a limited extent in lipohyperplasia dolorosa. On the whole, the main symptom "pain" is multi-faceted. The study initiated by the German Federal Joint Committee (G-BA) must therefore be viewed critically. Congenital (as opposed to acquired) lipoedema fat on the extremities significantly impairs a person's ability to undertake activities in general as well as leisure activities. Since no objectively verifiable findings in lipoedema can be ascertained thus far, the diagnosis should be based on a careful patient survey.

OBJECTIVE: The aim of this qualitative review is to provide an update on the current understanding of the genetic determinants of lipedema and to develop a genetic test to differentiate lipedema from other diagnoses. MATERIALS AND METHODS: An electronic search was conducted in MEDLINE, PubMed, and Scopus for articles published in English up to March 2019. Lipedema and similar disorders included in the differential diagnosis of lipedema were searched in the clinical synopsis section of OMIM, in GeneCards, Orphanet, and MalaCards. RESULTS: The search identified several genetic factors related to the onset of lipedema and highlighted the utility of developing genetic diagnostic testing to help differentiate lipedema from other diagnoses. CONCLUSIONS: No genetic tests or guidelines for molecular diagnosis of lipedema are currently available, despite the fact that genetic testing is fundamental for the differential diagnosis of lipedema against Mendelian genetic obesity, primary lymphedema, and lipodystrophies.

Background: The Stemmer sign is a physical examination finding used to diagnose lymphedema. If the examiner cannot pinch the skin of the dorsum of the foot or hand then this positive finding is associated with lymphedema. The purpose of the study was to determine the accuracy of the Stemmer sign to predict lymphedema. Methods: All patients referred to our Lymphedema Program between 2016 and 2018 were tested for the Stemmer sign and underwent lymphoscintigraphy to define the patient’s lymphatic function. Patient age, lymphedema type (primary and secondary), disease location (arm and leg), lymphoscintigraphy findings, stage, severity, and body mass index were recorded. Comparison of predictive variables and Stemmer sign result was performed using Fisher’s exact test and Student’s t test. Results: One hundred ten patients were studied: patients with a positive Stemmer sign (n = 87) exhibited abnormal (n = 80) or normal (n = 7) lymphatic function by lymphoscintigraphy (sensitivity = 92%). False-positive Stemmer signs included individuals with obesity (n = 6) or spinal muscle atrophy (n = 1). Subjects with a negative Stemmer sign (n = 23) had normal (n = 13) or abnormal (n = 10) lymphatic function by imaging (specificity = 57%). Patients with a false-negative Stemmer sign were more likely to have a normal body mass index (P = 0.02) and Stage 1 disease (P = 0.01). Conclusions: A positive Stemmer sign is a sensitive predictor for primary and secondary lymphedema of the arms or legs and, thus, is a useful part of the physical examination. Because the test exhibits moderate specificity, lymphoscintigraphy should be considered for patients with a high suspicion of lymphedema that have a negative Stemmer sign.