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Einleitung: Die Diagnostik des Lipödems basiert bislang auf rein klinischen Befunden, objektive Parameter fehlen bislang. Ziel dieser Studie ist es, einen möglichen Zusammen-hang zwischen einer standardisierten, sonographisch gemessenen Kompressibilität der subkutanen Fettschicht sowie dem Vergleich der Hautfettfalten an Abdomen und Oberschenkel und der klinischen Diagnose Lipödem aufzuzeigen. Material und Methode: Das Grundkollektiv zur Probandinnen-Auswahl bestand aus 1100 Patientinnen und Patienten. Davon wurden 1016 Patientinnen und Patienten wegen zutreffender Ausschlusskriterien ausgeschlossen. Die verbliebenen 84 Patientinnen wurden auf die klinische Diagnose „Lipödem der Beine“ untersucht. Die klinische Diagnose „Lipödem“ war bei 71 Patientinnen positiv und bei 13 Patientinnen negativ. Insgesamt haben drei Patientinnen die Teilnahme verweigert (eine mit negativer Diagnose, zwei mit positiver Diagnose); damit wurden 69 Patientinnen in der Gruppe der Lipödempatientinnen und zwölf Patientinnen in der Kontrollgruppe untersucht. Zudem wurden als weitere Kontrollgruppe sieben männliche „gesunde“ Probanden mit derselben Technik vermessen und verglichen. An Daten wurden für alle Probandinnen und Probanden das Alter, BMI, Verhältnis von Abdomen- zu Oberschenkelhautfettfalte (nur rechts), Subkutisdicke am Oberschenkel unkomprimiert und komprimiert auf beiden Seiten erhoben. Resultate: Die Annahme, dass die Subkutis bei Lipödempatientinnen deutlich geringer kompressierbar ist, konnte an 69 Lipödempatientinnen, die keinerlei Lymphödemsymptomatik zeigten, verifiziert werden. Die Kontrollgruppen (sieben Männer, zwölf Frauen) verhielten sich diesbezüglich negativ. Der Mittelwert dieser Kompressibilität lag in der Lipödemgruppe bei 7 %, in den Kontrollgruppen bei 22 % (Männer) bzw. 16 % (Frauen ohne Lipödem). Das Verhältnis der Hautfettfalten an Abdomen und Oberschenkel war bei Lipödempatientinnen mit im Mittel 0,43 signifikant unter den anderen Gruppen (Männer: 1,45; Frauen ohne Lipödem: 1,16). Diskussion: Die sonographisch gemessene Kompressibilität der Subkutis stellt einen wichtigen, objektiven Parameter zur Diagnostik des Lipödems dar. Eine zusätzliche positive Aussage liefert zudem der Vergleich der Hautfettfaltendicke an Abdomen und Oberschenkel mit statistisch signifikanten Unterschieden.

BACKGROUND: Although a large number of adult women worldwide are affected by lipedema, the physiologic conditions triggering onset and progression of this chronic disease remain enigmatic. In the present study, a descriptive epidemiologic situation of postoperative lipedema patients is presented. METHODS: The authors developed an online survey questionnaire for lipedema patients in Germany. The survey was conducted on 209 female patients who had been diagnosed with lipedema and had undergone tumescent liposuction. RESULTS: Most of the participants (average age, 38.5 years) had noticed a first manifestation of the disease at the age of 16. It took a mean of 15 years to accomplish diagnosis. Liposuction led to a significant reduction of pain, swelling, tenderness, and easy bruising as confirmed by the majority of patients. Hypothyroidism [n = 75 (35.9 percent) and depression [n = 48 (23.0 percent)] occurred at a frequency far beyond the average prevalence in the German population. The prevalence of diabetes type 1 [n = 3 (1.4 percent)], and diabetes type 2 [n = 2 (1 percent)] was particularly low among the respondents. Forty-seven of the lipedema patients (approximately 22.5 percent) suffered from a diagnosed migraine. Following liposuction, the frequency and/or intensity of migraine attacks became markedly reduced, as stated by 32 patients (68.1 percent). CONCLUSIONS: Quality of life increases significantly after surgery with a reduction of pain and swelling and decreased tendency to easy bruising. The high prevalence of hypothyroidism in lipedema patients could be related to the frequently observed lipedema-associated obesity. The low prevalence of diabetes, dyslipidemia, and hypertension appears to be a specific characteristic distinguishing lipedema from lifestyle-induced obesity.

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.

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.

Background: Although lipedema is often clinically distinguished from lymphedema, there is considerable overlap between the 2 entities. The purpose of this study was to evaluate lymphoscintigraphic findings in patients with lipedema to better characterize lymphatic flow in this patient population. Methods: This is an updated 4 year experience containing significant new information of patients with lipedema receiving lymphoscintigraphy at our institution between January 2015 and October 2017. Patient demographics, clinical characteristics, and lymphoscintigraphic findings were extracted. Klienhan’s transport index (TI) was utilized to assess lymphatic flow in patient’s lower extremities (LEs). Scores range from 0-45, with values >10 denoting pathologic lymphatic transport. Results: 19 total patients with lipedema underwent lymphoscintigraphic evaluation. Mean age was 54.8 and mean BMI was 35.9 kg/m2. Severity of lipedema was classified as stage 1 in 5 patients (26.3%), stage 2 in 4 patients (21.1%), stage 3 in 4 patients (21.1%), and stage 4 in 6 patients (31.6%). The mean TI for all extremities was 12.5. 24 (63.2%) LEs had a pathologic TI , including 7 LEs with stage 1 (29.2%), 3 LEs with stage 2 (12.5%), 6 LEs with stage 3 (25.0%), and 8 LEs with stage 4 lipedema (33.3%). The mean TI was significantly greater for extremities with severe (stage 3/4) lipedema than those with mild or moderate (stage 1/2) lipedema (15.1 vs. 9.7, p=0.049). Mean difference in TI scores between each LE for individual patients was 6.43 (SD 7.96). Conclusions: Our results suggest that patients with lipedema have impaired lymphatic transport, and more severe lipedema may be associated with greater lymphatic transport abnormalities.

BACKGROUND: Lipedema is characterized by localized accumulation of fat in the extremities, which is typically unresponsive to dietary regimens or physical activity. Although the disease is well described and has a high incidence, little is known regarding the molecular and cellular mechanisms underlying its pathogenesis. The aim of this study was to investigate the pathophysiology of lipedema adipose cells in vitro. METHODS: Adipose-derived stem cells were isolated from lipoaspirates derived from lipedema and nonlipedema patients undergoing tumescent liposuction. In vitro differentiation studies were performed for up to 14 days using adipogenic or regular culture medium. Supernatants and cell lysates were tested for adiponectin, leptin, insulin-like growth factor-1, aromatase (CYP19A1), and interleukin-8 content at days 7 and 14, using enzyme-linked immunosorbent assays. Adipogenesis was evaluated by visualizing and measuring cytoplasmic lipid accumulation. RESULTS: Lipedema adipose-derived stem cells showed impeded adipogenesis already at early stages of in vitro differentiation. Concomitant with a strongly reduced cytoplasmic lipid accumulation, significantly lower amounts of adiponectin and leptin were detectable in supernatants from lipedema adipose-derived stem cells and adipocytes compared with control cells. In addition, lipedema and nonlipedema cells differed in their expression of insulin-like growth factor-1, aromatase (CYP19A1), and interleukin-8 and in their proliferative activity. CONCLUSIONS: The authors' findings indicate that in vitro adipogenesis of lipedema adipose-derived stem cells is severely hampered compared with nonlipedema adipose-derived stem cells. Lipedema adipose cells differ not only in their lipid storage capacity but also in their adipokine expression pattern. This might serve as a valuable marker for diagnosis of lipedema, probably from an early stage on.

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.

INTRODUCTION: Lipedema is a barely recognized and poorly diagnosed, but common disease affecting almost exclusively female patients. The pathomechanism of lipedema is not known, and clinically, it is a bilateral, symmetrical, disproportional fatty enlargement of the lower half of the body, the disease does not affect the feet, and the upper extremities are often involved. Since lipedema is associated with increased aortic stiffness and altered left ventricular (LV) rotational mechanics, the present study was designed to compare the size and function of the mitral annulus (MA) between lipedema patients and controls by three-dimensional speckle-tracking echocardiography (3DSTE). METHODS: Twenty-four patients with stage 2 lipedema and 48 age-, gender-, and body mass index-matched healthy control patients were included in the study. Each person from the lipedema and the control groups underwent two-dimensional Doppler echocardiography and 3DSTE. RESULTS: Significantly enlarged left atrial diameter, LV end-diastolic diameter and volume, and LV end-systolic volume could be detected in lipedema patients as compared to controls. None of the lipedema patients and controls showed ≥grade 1 mitral or tricuspid regurgitation. Dilated end-systolic and end-diastolic MA diameter, area, and perimeter could be demonstrated in lipedema patients as compared to controls, and these changes were accompanied by impaired MA fractional area change at rest. Following 1-hour use of compression stockings, no significant improvement was seen in these parameters. CONCLUSIONS: Lipedema is associated with MA enlargement and functional impairment. The use of compression stockings does not improve these alterations.

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.

Background: Metastatic tumor cells spread through lymphatic vessels and colonize draining lymph nodes (LNs). It is known that tumors induce lymphangiogenesis to enhance lymphatic metastasis and that metastatic cancer cells are carried by lymph flow to LNs. Methods and Results: Here, we investigated the molecular and cellular regulation of collecting lymphatic vessel contraction in vessels draining a metastatic tumor using intravital microscopy. In tumor-draining collecting lymphatic vessels, we found vessel contraction was suppressed. The infiltration of peritumor tissue by inducible nitric oxide synthase positive and CD11b+Gr1+ myeloid cells played a critical role in the suppression of lymphatic contraction. Depletion of Gr1+ cells with an anti-Gr1 antibody improved contraction of tumor-draining lymphatic vessels. In addition, inducing tumor cell death restored lymphatic contraction in nude mice. Conclusions: These findings indicate that tumors contribute to regulation of lymphatic transport in a reversible manner, warranting further investigation into the role of impaired lymphatic transport in cancer progression.

Background: Lymphedema and chronic edema is a major health care problem in both developed and nondeveloped countries The Lymphoedema Impact and Prevelance - International (LIMPRINT) study is an international health service-based study to determine the prevalence and functional impact in adult populations of member countries of the International Lymphoedema Framework (ILF). Methods and Results: A total of 1051 patients from eight centers in Turkey were recruited using the LIMPRINT study protocol. Data were collected using the core and module tools that assess the demographic and clinical properties as well as disability and quality of life (QoL). Most of the Turkish patients were recruited from specialist lymphedema services and were found to be women, housewives, and having secondary lymphedema because of cancer treatment. The duration of lymphedema was commonly <5 years and most of them had International Society of Lymphology (ISL) grade 2 lymphedema. Cellulitis, infection, and wounds were uncommon. The majority of patients did not get any treatment or advice before. Most of the patients had impaired QoL and decreased functionality, but psychological support was neglected. Although most had social health security access to lymphedema centers, nevertheless access seemed difficult because of distance and cost. Conclusion: The study has shown the current status and characteristics of lymphedema patients, treatment conditions, the unmet need for the diagnosis and treatment, as well as burden of the disease in both patients and families in Turkey. National health policies are needed for the prevention, diagnosis, and treatment in Turkey that utilize this informative data.

Obese adipose tissue expansion is an inflammatory process that results in dysregulated lipolysis, increased circulating lipids, ectopic lipid deposition, and systemic insulin resistance. Lymphatic vessels provide a route of fluid, macromolecule, and immune cell clearance, and lymphangiogenesis increases this capability. Indeed, inflammation-associated lymphangiogenesis is critical in resolving acute and chronic inflammation, but it is largely absent in obese adipose tissue. Enhancing adipose tissue lymphangiogenesis could, therefore, improve metabolism in obesity. To test this hypothesis, transgenic mice with doxycycline-inducible expression of murine vascular endothelial growth factor (VEGF)-D under a tightly controlled Tet-On promoter were crossed with adipocyte-specific adiponectin-reverse tetracycline-dependent transactivator mice (Adipo-VD) to stimulate adipose tissue-specific lymphangiogenesis during 16-week high-fat diet-induced obesity. Adipose VEGF-D overexpression induced de novo lymphangiogenesis in murine adipose tissue, and obese Adipo-VD mice exhibited enhanced glucose clearance, lower insulin levels, and reduced liver triglycerides. On β-3 adrenergic stimulation, Adipo-VD mice exhibited more rapid and increased glycerol flux from adipose tissue, suggesting that the lymphatics are a potential route of glycerol clearance. Resident macrophage crown-like structures were scarce and total F4/80+ macrophages were reduced in obese Adipo-VD s.c. adipose tissue with evidence of increased immune trafficking from the tissue. Augmenting VEGF-D signaling and lymphangiogenesis specifically in adipose tissue, therefore, reduces obesity-associated immune accumulation and improves metabolic responsiveness.

Background: Chronic edema/lymphedema is defined as edema present for more than 3 months. It is underrecognized and undertreated. The International Lymphedema Framework developed an international study, Lymphedema Impact and Prevalence International (LIMPRINT), to estimate the prevalence and impact of chronic edema in heterogeneous populations. Canada participated in this study. Methods and Results: Participants were recruited from an outpatient chronic wound management clinic. At a study visit, the following tools were administered: The Core Tool, Demographics and Disability assessment (WHODAS 2.0), Quality-of-life assessment (LYMQOL + EQ-5D), Details of swelling, Wound assessment, and Cancer. Data were entered into an international database (Clindex), and country-specific data were analyzed. Sixty-eight subjects were enrolled. Fifty-seven percent were males and 43% females. More than 90% were older than 45 years. Only 7.35% had primary lymphedema. Most had lower extremity edema (65 of 68). Over half (47.06%) were morbidly obese with body mass index of >40. The most common underlying condition was venous disease. Only 8 of 68 had a history of cancer. While 72.06% had a history of cellulitis, only 10.2% had been hospitalized in the past year. 39.71% had an open wound. More than 75% had received multilayer bandaging, compression garments, wound dressings, and extensive counseling. Few had received manual lymphatic drainage, which is not funded. Disability was less than expected. Conclusion: Chronic edema/lymphedema is an underrecognized condition. These data and the wider LIMPRINT study are important tools to advocate for wider recognition and funding of treatment by health care systems.

Lipedema is a painful disease of subcutaneous adipose tissue leading to bilateral increase of leg and/or arm volume, but sparing hands and feet. Although conservative treatment with complex decongestive therapy has been considered as the fundamental treatment, micro-cannular liposuction in tumescent anesthesia has become a surgical option. We report on 111 patients mostly with advanced lipedema treated by this technique in our center between 2007 and 2018. The median age of the patients was 44 years. Eighty percent of patients had at least one comorbidity. There was an association of longstanding and advanced disease to obesity and diseases of the metabolic syndrome-spectrum. The median total amount of lipoaspirate was 4,700 ml, with a range of 950-14,250 ml. The median reduction of limb circumference was 6 cm. The median pain level before treatment was 7.8 and 2.2 at the end of the treatment. An improvement of mobility could be achieved in all patients. Bruising was also reduced. Serious adverse events were observed in 1.2% of procedures, the infection rate was 0% and the bleeding rate was 0.3%. Liposuction is an effective treatment for painful lipedema. The procedure should be performed in specialized centers.

Current clinical methods for the evaluation of lymphatic vessel function, crucial for early diagnosis and evaluation of treatment response of several pathological conditions, in particular of postsurgical lymphedema, are based on complex and mainly qualitative imaging techniques. To address this unmet medical need, we established a simple strategy for the painless and quantitative assessment of cutaneous lymphatic function. We prepared a lymphatic-specific tracer formulation, consisting of the clinically approved near-infrared fluorescent dye, indocyanine green, and the solubilizing surfactant Kolliphor HS15. The tracer was noninvasively delivered to the dermal layer of the skin using MicronJet600 hollow microneedles, and the fluorescence signal decay at the injection site was measured over time using a custom-made, portable detection device. The decay rate of fluorescence signal in the skin was used as a direct measure of lymphatic vessel drainage function. With this method, we could quantify impaired lymphatic clearance in transgenic mice lacking dermal lymphatics and distinguish distinct lymphatic clearance patterns in pigs in different body locations and under manual stimulus. Overall, this method has the potential for becoming a noninvasive and quantitative clinical "office test" for lymphatic function assessment.

Background and Aim: Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women. Methods: Forty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to <30 kg/m2) and Obese (BMI 30 to <40 kg/m2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF. Results: Non-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p < 0.005) and Obese (p < 0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p < 0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p < 0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls. Conclusion: Hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.