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Lipohyperplasia dolorosa (LiDo), also known as lipedema, is a painful subcutaneous adipose tissue disorder. While the characteristic bilateral accumulation of adipocytes in extremities sparing hands and feet is investigated, an objective characterization of pain and the sensory system of LiDo patients is missing. Accordingly, progress to overcome the unsatisfying response to pain-therapeutics of patients of this widespread, lifelong, and severe disease is missing. We characterized the sensory detection profile of painful and non-painful stimuli in 20 non-obese LiDo patients and 20 waist-to-height-ratio matched controls using the clinically approved QST-protocol of the German Research Association on Neuropathic Pain (DFNS e.V.). Further, pain-reports and participants’-psychometry was assessed using the German Pain Questionnaire. LiDo patients showed no overt psychometric abnormalities. LiDo pain appeared as somatic rather than neuropathic or psychosomatic aversive. All QST measurements were normal with the selective exception of two: The pressure pain threshold (PPT) was strongly reduced and the vibration detection threshold (VDT) was strongly increased selectively at the affected thigh. In contrast, sensory profiles at the dorsum of the hand were normal. ROC-analysis of the combination of PPT and VDT of thigh versus hand shows high sensitivity and specificity, categorizing correctly 96.5% of the measured participants as LiDo patients or healthy controls, respectively. Thus, we propose to assess both, PPT and VDT, at the painful thigh and the pain-free hand as basis to develop a combined PVTH-score for differential diagnosis as a fast and convenient bedside test for the identification of non-obese LiDo patients.

In blog posts and other documents, the Lipedema Foundation sometimes presents data on growth in a number of publications in Lipedema research. For example, a statistic we often like to cite is that 50% of primary data papers on Lipedema have been published in the past 5 years. This information can b

Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses.

Introduction: Lipedema is a bilateral enlargement of the legs due to abnormal depositions of subcutaneous fat. Recent studies using lymphoscintigraphy documented that lipedema associates with lymphatic alterations. It is still not known, whether non-lipedema obesity also leads to similar lymphoscintigraphic changes within lower legs. Clinically, both, lipedema and obesity may progress to secondary lymphedema. The aim of the study was to evaluate lymphoscintigraphy of lower limbs in women with lipedema in comparison to overweight/obese women. Methods: 51 women (in the mean age of 43.3 ± 13.56) with the diagnosis of lipedema and 31 women (in the mean age of 44.7 ± 13.48) with overweight/obesity were enrolled into the study. Women in both study groups had no clinical signs of lymphedema. The groups were matched by mean volume of their legs, calculated using the formula for a truncated cone. Lymphoscintigraphy was evaluated in every women qualitatively. Body composition parameters were assessed using bioelectric impedance analysis (BIA). Results: Lymphoscintigraphic alterations within lower extremities were similar in both, lipedema and overweight/obese groups and were present in majority of women in both study groups. The most common lymphoscintigraphic alteration in both groups were additional lymphatic vessels (in the lipedema group observed in 76.5% of patients and in the overweight/obesity group – in 93.5%). Visualization of popliteal lymph nodes and dermal backflow were observed respectively in 33% and in 5.9% in the group with lipedema and in 45.2% and in 9.7% in the overweight/obesity group. There were significant relationships between severity of lymphoscintigraphic alterations and weight, lean body mass (LBM), total body water (TBW), volume of both legs and thigh circumference in the lipedema group. Such relationships were absent in the overweight/obesity group. Discussion: Our study indicates that lymphatic alterations are present before development to clinically visible secondary lymphedema in both conditions, lipedema and overweight/obesity. In majority of women from both study groups they indicate rather an overload of the lymphatic system than insufficiency. Lymphoscintigraphic alterations are similar in both groups, therefore, lymphoscintigraphy is not a diagnostic tool that might distinguish lipedema from overweight/obesity.

Lipoedema is an adipose tissue disorder almost exclusively affecting women. Evidence shows lipoedema is both poorly recognised and misdiagnosed which results in many women struggling to get a diagnosis and to gain access to specialist NHS services. This article aims to raise awareness of lipoedema and highlight the main role that community and primary care nurses can play in identifying this long-term condition earlier. It provides detail on the condition to help signpost, refer for diagnosis and initiate conservative management for those individuals with this challenging condition.

Abstract Lipedema is a wide-spread disease with painful accumulations of subcutaneous fat in legs and arms. Often obesity co-occurs. Many patients suffer from impairment in mobility and mental health. Obesity and mental health in turn can be positively influenced by physical activity. In this study we aimed to examine the interrelations between pain and physical activity on mental health in lipedema patients. In total, 511 female lipedema patients (age M = 40.16 ± 12.45 years, BMI M = 33.86 ± 7.80 kg/m 2 ) filled in questionnaires measuring pain (10-point scale), physical activity (7 Items; units per week), and mental health (PHQ-9; WHOQOL-BREF with subscales mental, physical, social, environmental, and overall health). Response surface analyses were calculated via R statistics. Explained variance was high for the model predicting depression severity (R 2  = .18, p < .001) and physical health (R 2  = .30, p < .001). Additive incongruence effects of pain and physical activity on depression severity, mental, physical, and overall health were found (all p < .001). In our study, physical activity and pain synergistically influenced physical, mental, and overall health. Pain did not only lead to low mental health but also interfered with the valuable potential of engaging in physical activity in lipedema patients.

Background: To define the usefulness of three-dimensional (3D) ultrasound diagnostics for lipedema. Methods and Results: In this study, starting in May 2021, it was decided to apply 3D ultrasound diagnostics in the evaluation of the tissue in 40 patients affected with lipedema (stage I-II-III) who arrived at the Pianeta Linfedema Study Centre. Furthermore, subjects with lipohypertrophy were also included in this study to evaluate the structural features of the adipo-fascia and eventual structural similarity with lipedema. With an adequate instrument (SonoScape 20-3D ultrasound) and probe (17 MHz) on bilateral symmetric marker points, the epidermis-dermis complex and subcutaneous tissue were evaluated. In all patients with lipedema, a normal ultrasound representation of the epidermis-dermis complex, the thickness of subcutaneous tissue, due to hypertrophy of the adipose lobules and of interlobular connective septa, the thickness of the fibers that connect the derma to superficial fascia, and the thickness of the superficial fascia itself as well as of the deep fascia have been highlighted; moreover, fibrotic connective areas in the connective septa that correspond to the palpable nodules has been highlighted. The structural feature, present in all the clinical stages, unexpectedly, was the presence along the superficial fascia of anechogenicity due to the presence of fluid. In lipohypertrophy, structural characteristics similar to those in the initial stage of lipedema have been highlighted. Conclusion: 3D ultrasound diagnostics have led to the discovery of important features of adipo-fascia in lipedema not previously highlighted by two-dimensional ultrasound diagnostic studies.

OBJECTIVE: Symmetrical bilateral lower extremity edema (BLEE) needs to be treated effectively. Finding the cause of this condition increases the success of treatment. Fluid increase in the interstitial space (FIIS) is always present as a cause or a result. Subcutaneously administered nanocolloid is transported by uptake by lymphatic pre-collectors, and this uptake takes place in the interstitium. We aimed to evaluate the interstitium with labeled nanocolloid and contribute to the differential diagnosis in cases with BLEE. METHODS: Our retrospective study included 74 female patients who underwent lymphoscintigraphy for bilateral lower extremity edema. Technetium 99m (Tc-99m) albumin colloid (nanocolloid), a marked colloidal suspension, was applied subcutaneously to two different areas on the dorsum of both feet with a 26 gauge needle The dose volume administered intradermally is approximately 0.2-0.3 ml, and each injector has 22-25MBq of activity. Siemens E-Cam dual-headed SPECT gamma camera was used for imaging. Dynamic and scanning images were taken with a high-resolution parallel hole collimator. Ankle images were re-evaluated by two nuclear medicine specialists, independent of physical examination and scintigraphy findings. RESULTS: 74 female patients with bilateral lower extremity edema were divided into two groups based on physical examination and lymphoscintigraphy findings. There were 40 and 34 patients in Groups I and II, respectively. In the physical examination, patients in Group I were evaluated as lymphedema, and patients in Group II were evaluated as lipedema. The main lymphatic channel (MLC) was not observed in any of the patients in Group I in the early images, and the MLC was observed at a low level in the late imaging in 12 patients. The sensitivity of the presence of distal collateral flows (DCF) in the presence of significant MLC in early imaging in demonstrating increased fluid in the interstitial space (FIIS) was calculated as 80%, specificity as 80%, PPV 80%, and NPV 84%. CONCLUSIONS: While MLC is present in early images, concomitant DCF occurs in cases of lipoedema. The transport of increased lymph fluid production in this group of patients can be covered by the existing MLC. Although MLC is evident, the presence of significant DCF supports the presence of lipedema. It can be used as an important parameter in the diagnosis in early cases where physical examination findings are not evident.

Abstract Background and Aim: Chronic lower extremity edema has been associated with postural impairment, sacroiliac joint dysfunction (SIJD), and abnormal gait. Lymphedema and lipedema are important chronic lower extremity causes. This study aimed to detect the presence of SIJD and postural disorders in patients with lower extremity edema and the relationship between them. Methods: This is a comparative, prospective cohort study. Fifty-three patients with lower extremity edema and 53 healthy subjects were included in the study. Pain provocation tests were used to determine SIJD. Postural analysis was conducted with PostureScreen® Mobile 11.2 (PostureCo, Inc., Trinity, FL) software. The life quality of participants was determined by the Lymphedema Quality of Life (LYMQOL) scale. The functional status of the patients was determined by the Oswestry Disability Index and Lower Extremity Functional Scale. Results: SIJD (18.9%) was more common in the edema group. There was a positive correlation between volume differences, percentages, and the development of SIJD. We found deviations in the head, shoulder, and hip angulations in the edema group. Q angle and lateral shoulder angulation were significantly higher in patients with SIJD in the edema group. In the edema group, LYMQOL-leg total score was higher in patients with SIJD. Conclusion: Chronic lower extremity edema was found to be associated with postural deviations and SIJD. Besides edema control, postural disorders and SIJD should also be considered in these patients.

Lipedema is still a little-known disease, and the internet and social networks have been increasing the identification of many people with the condition, its characteristics, and diagnostic criteria. It is a disease of the adipose tissue that causes changes in body shape in the regions of the body's extremities, hips, and thighs. Classification of lipedema is based on the distribution of adipose tissue and severity of the disease (stages I, II, III, and IV) [ [1] ]. Lymphedema, venous disease, and hypermobile joints are co-morbidities [ [2] ]. Its overlap with overweight and obesity is common. Also, weight fluctuations and metabolic changes stem from body dissatisfaction commonly affecting women.

BACKGROUND: Lipedema is a progressive disease, diagnosed most often in women, which is characterized by the unproportionate and symmetrical distribution of adipose tissue primarily in the extremities. Despite numerous results from in vitro and in vivo studies, many questions regarding the pathology and genetic background of lipedema have remained unanswered. METHODS: Adipose tissue-derived stromal/stem cells (ASCs) were isolated from lipoaspirates derived from non-obese and obese lipedema and non-lipedema donors. Growth/morphology, metabolic activity, differentiation potential and gene expression were evaluated using quantification of lipid accumulation, metabolic activity assay, live-cell imaging, RT-PCR, quantitative PCR and immunocytochemical staining. RESULTS: The adipogenic potential of lipedema and non-lipedema ASCs did not rise in parallel with the donors' BMI and did not differ significantly between groups. However, in vitro differentiated adipocytes from non-obese lipedema donors showed significant upregulation of adipogenic gene expression compared to non-obese controls. All other genes tested were equally expressed in lipedema and non-lipedema adipocytes. The ADIPOQ/LEP ratio (ALR) was significantly reduced in adipocytes from obese lipedema donors compared to their non-obese lipedema counterparts. Increased stress fiber-integrated SMA was visible in lipedema adipocytes compared to non-lipedema controls and appeared enhanced in adipocytes from obese lipedema donors. CONCLUSIONS: Not only lipedema per se but also BMI of donors impact adipogenic gene expression substantially in vitro. The significantly reduced ALR and the increased occurrence of myofibroblast-like cells in "obese" lipedema adipocyte cultures underlines the importance of attention towards the co-occurrence of lipedema and obesity. These are important findings towards accurate diagnosis of lipedema.

Expert representatives from 11 professional societies, as part of an autonomous work group, researched and developed appropriate use criteria (AUC) for lymphoscintigraphy in sentinel lymph node mapping and lymphedema. The complete findings and discussions of the work group, including example clinical scenarios, were published on October 8, 2022, and are available at https://www.snmmi.org/ClinicalPractice/ content.aspx?ItemNumber=42021. The complete AUC document includes clinical scenarios for scintigraphy in patients with breast, cutaneous, and other cancers, as well as for mapping lymphatic flow in lymphedema. Pediatric considerations are addressed. These AUC are intended to assist health care practitioners considering lymphoscintigraphy. Presented here is a brief overview of the AUC, including the rationale and methodology behind development of the document. For detailed findings of the work group, the reader should refer to the complete AUC document online.

Lipoedema is characterized by disproportionate painful fat accumulation mostly in the lower limbs. The presence of lymphoedema in lipoedema remains controversial. This study aimed to assess the presence or absence of lymphoedema in the lower limbs of women with lipoedema using indocyanine green (ICG) lymphography. A cross-sectional retrospective study was undertaken in women with a clinical diagnosis of lipoedema whose lower limbs were examined with ICG lymphography. MD Anderson Cancer Center (MDACC) ICG staging was used to determine lymphoedema presence and severity. Patient characteristics, ICG lymphography findings, Stemmer sign, body mass index, waist-to-hip ratio, limb volume and bioimpedance spectroscopy measures were recorded. Forty women with lipoedema underwent ICG lymphography for the lower limbs from January 2018 to July 2022. Thirty-four women (85.0%) were determined by ICG lymphography as MDACC ICG Stage 0 representing normal lymphatics. Of the six women who demonstrated dermal backflow on ICG lymphography, all were determined as ICG Stage 1, four had localized traumatic dermal backflow area at their ankles, one had previously diagnosed with primary lymphoedema and one was classified as lipoedema stage 4. ICG lymphography findings suggested the absence of lymphoedema in a clear majority of women with lower limb lipoedema.

Liposuction plays an important role as a surgical treatment option for lipoedema. This document serves to critically review the evidence in the literature, as well as explain the differences between the lipoedema population compared to the aesthetic surgery population undergoing liposuction. It is not a comprehensive text on lipoedema management but serves to guide surgeons. This guidance was produced on behalf of the British Association of Aesthetic Plastic Surgeons (BAAPS) and British Association of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS) by the expert liposuction group. The guidance is based on evidence available in the literature along with specialist expert opinion on liposuction for lipoedema to provide plastic surgeons with consensus recommendation for surgical treatment. The aim is to identify best practice to maximise the safety of patients. This article summarises current practises and safety considerations and outlines recommendations covering various aspects of patient care.

OBJECTIVE: This study examines the role of MTHFR gene polymorphism (rs1801133) in women with lipedema (LIPPY) body composition parameters compared to a control group (CTRL). SUBJECTS AND METHODS: We carried out a study on a sample of 45 LIPPY and 50 women as a CTRL. Body composition parameters were examined by Dual-energy X-ray Absorptiometry (DXA). A genetic test was performed for the MTHFR polymorphism (rs1801133, 677C>T) using a saliva sample for LIPPY and CTRL groups. Mann-Whitney tests evaluated statistically significant differences between four groups (carriers and non-carriers of the MTHFR polymorphism for LIPPY and CTRL groups) on anthropometric/body composition parameters to identify patterns. RESULTS: LIPPY showed significantly higher (p<0.05) anthropometric parameters (weight, BMI, waist, abdominal, hip circumferences) and lower waist/hip ratio (p<0.05) compared to the CTRL group. The association between the polymorphism alleles related to the rs1801133 MTHFR gene and the body composition values LIPPY carriers (+) showed an increase in fat tissue of legs and fat region of legs percentage, arm’s fat mass (g), leg’s fat mass (g), and leg’s lean mass (g) (p<0.05) compared to CTRL (+). Lean/fat arms and lean/fat legs were lower (p<0.05) in LIPPY (+) than in CTRL (+). In the LIPPY (+), the risk of developing the lipedema disease was 2.85 times higher (OR=2.85; p<0.05; 95% confidence interval = 0.842-8.625) with respect to LIPPY (-) and CTRL. CONCLUSIONS: The presence or absence of MTHFR polymorphism offers predictive parameters that could better characterize women with lipedema based on the association between body composition and MTHFR presence.

The disease "Lipedema", which has been known since 1940, is increasingly better understood. Dimpled edema in particular is not significant in women with fat distribution disorders on the arms and legs. These and other scientific findings are "work in progress" with the aim of renaming the disease. A "proper name" is "Lipohyperplasia dolorosa" (LiDo). With LiDo, the increase in volume is genetically fixed, but the pain is dynamically progressive. A LiDo must be distinguished from other symmetrical, painless fat distribution disorders on the arms and legs at first sight and after palpatory examination, especially from the occasionally coincident obesity. Obesity is never comorbid, but often coincident with LiDo. Although physical activity and a change in diet can reduce obesity, they cannot eliminate the disproportionate increase in fat tissue on the extremities that is exclusively caused by LiDo. In LiDo patients coincident with obesity, gastric surgery has no effect on the obligatory pain. There are both conservative and surgical treatment options for LiDo. A procedure that has been established since 1997 is surgical treatment using lymphological liposculpture. As part of this operation, large wounds are created under the skin, which, according to the "Rules of Nine" when treating both arms in one session and the suction of the legs in 2 sessions per operation, correspond to an area of ​​18% of the body surface. However, with adequate postoperative management and the administration of antibiotics and antithrombotics, local complications associated with the operation are rare. The most important result of consistent surgical treatment of lipohyperplasia dolorosa is the impact on quality of life: "It ruined her life" becomes "It improves her life".

(1) Background: Although lipedema has gained more interest among researchers, specific treatment methods are still unknown. This study aims to identify the effects of compression therapy combined with exercises compared to exercising only. Moreover, the aim is to assess the methodology and outcome measurements before conducting a larger study. (2) Methods: Six women with lipedema were enrolled in the study; three were undergoing exercise program and compression therapy using compression leggings, and the remaining three were undergoing exercises only. During the first 4 weeks, intervention was under the supervision of a physiotherapist, and in the remaining weeks, participants were exercising independently. Measurements of circumference, weight, thickness of the skin and adipose tissue, symptom severity, and quality of life were taken at baseline, after 4 weeks and after 6 weeks; (3) Results: There was a significant decrease in the subjectively reported tendency for bruising and pain at palpation among patients that received compression therapy. Additionally, there was a tendency to reduce or maintain the circumference of the legs in patients using compression, while it tended to increase in patients without compression. (4) Conclusions: Preliminary results indicate that compression therapy, combined with exercises, could improve the quality of life and decrease the severity of lipedema symptoms. Further studies on a large clinical group are advisable.

Lipedema is a chronic adipose tissue disorder affecting approximately 11% of women worldwide. The illness is often misdiagnosed as obesity, and because of this, women often struggle in meetings with healthcare providers. Few studies have assessed these encounters of younger women with lipedema. The aims of this qualitative study were to explore women’s experiences in meetings with healthcare providers and the importance of social support and belonging, with a focus on younger women. Fifteen women with lipedema between the ages of 21 and 47 years (mean age 36.2 years) were interviewed. The results indicated that women felt stigmatized by healthcare providers and that younger women in their 20s and early 30s struggled more often than women of higher age when receiving their diagnosis. The feeling of shame and stigma were also dependent on the woman’s resources in handling the illness. The younger women reported that their self-confidence and romantic relationships were challenging. Social support and the feeling of belonging through romantic relationships or support groups were important resources for managing the illness. Highlighting the experiences of women may aid in increasing recognition and knowledge of lipedema. This in turn may reduce the stigma and lead to equitable healthcare services.

When studying the current literature, one might get the impression that lipedema is a “modern” disease, with increasing incidence and augmenting prevalence throughout Western countries during the last decade. However, a quick look into older textbooks shows that disproportionate accumulation of fat in female bodies has long been known without being recognized as an independent disease. Nevertheless, it was not until 1940 that Allen and Hines described a “syndrome characterized by fat legs and orthostatic edema” in a seminal publication. The mere awareness that people who have lipedema are not just overweight but suffer from a yet poorly defined pathological condition, may be considered a decisive leap forward in the understanding of lipedema. A number of comprehensive publications have since dealt with the clinical presentation of lipedema and have provided the first clues towards the potential pathological mechanisms underlying its initiation and progression. Nevertheless, despite all effort that has been undertaken to unravel lipedema pathology, many questions have remained unanswered. What can be deduced with certainty from all experimental and medical evidence available so far is that lipedema is neither a cosmetic problem nor is it a problem of lifestyle but should be accepted as a serious disease with yet undetermined genetic background, which makes women’s lives unbearable from both a physical and psychological point of view. To date, results from clinical inspections have led to the categorization of various types and stages of lipedema, describing how the extremities are affected and evaluating its progression, as demonstrated by skin alterations, adipose tissue volume increase and physical and everyday-behavioral impediments. There is accumulating evidence showing that advanced stages of lipedema are usually accompanied by excessive weight or obesity. Thus, it is not unreasonable to assume that the progression of lipedema is largely driven by weight gain and the pathological alterations associated with it. Similarly, secondary lymphedema is frequently found in lipedema patients at advanced stages. Needless to say, both conditions considerably blur the clinical presentation of lipedema, making diagnosis difficult and scientific research challenging. The present literature review will focus on lipedema research, based on evidence fromex vivo and in vitro data, which has accumulated throughout the last few decades. We will also open the discussion as to whether the currently used categorization of lipedema stages is still sufficient and up-to-date for the accurate description of this enigmatic disease, whose name, strangely enough, does not match its pathologic correlate.