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Liposuction is a procedure commonly performed in the UK usually with a low incidence of serious sequelae; however with larger patients and increased volumes of lipoaspirate, complications have been reported more frequently. One of the rare but very serious complications postliposuction is fat embolism syndrome (FES), a life-threatening condition difficult to diagnose and limited in treatment. The authors present the case of a 45-year-old woman who was admitted to the intensive care unit postelective liposuction for bilateral leg lipoedema. She presented with the triad of respiratory failure, cerebral dysfunction and petechial rash requiring a brief period of organ support. This case highlights that with the recent increase in liposuction procedures worldwide, FES is a differential to always consider. Although still a rare condition this article emphasises the importance of thinking outside the box and how to identify and manage such a lifethreatening complication.

Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

BACKGROUND: Lipedema is a condition consisting of painful bilateral increases in subcutaneous fat and interstitial fluid in the limbs with secondary lymphedema and fibrosis during later stages. Combined decongestive therapy (CDT) is the standard of care in most countries. Since the introduction of tumescent technique, liposuction has been used as a surgical treatment option. The aim of this study was to determine the outcome of liposuction used as treatment for lipedema. METHODS: Twenty-five patients who received 72 liposuction procedures for the treatment of lipedema completed a standardized questionnaire. Lipedema-associated complaints and the need for CDT were assessed for the preoperative period and during 2 separate postoperative follow-ups using a visual analog scale and a composite CDT score. The mean follow-up times for the first postoperative follow-up and the second postoperative follow-up were 16 months and 37 months, respectively. RESULTS: Patients showed significant reductions in spontaneous pain, sensitivity to pressure, feeling of tension, bruising, cosmetic impairment, and general impairment to quality of life from the preoperative period to the first postoperative follow-up, and these results remained consistent until the second postoperative follow-up. A comparison of the preoperative period to the last postoperative follow-up, after 4 patients without full preoperative CDT were excluded from the analysis, indicated that the need for CDT was reduced significantly. An analysis of the different stages of the disease also indicated that better and more sustainable results could be achieved if patients were treated in earlier stages. CONCLUSIONS: Liposuction is effective in the treatment of lipedema and leads to an improvement in quality of life and a decrease in the need for conservative therapy.

BACKGROUND AIMS: Lipedema is a hormone-related disease of women characterized by enlargement of the extremities caused by subcutaneous deposition of adipose tissue. In healthy patients application of autologous adipose tissue-derived cells has shown great potential in several clinical studies for engrafting of soft tissue reconstruction in recent decades. The majority of these studies have used the stromal vascular fraction (SVF), a heterogeneous cell population containing adipose-derived stromal/stem cells (ASC), among others. Because cell identity and regenerative properties might be affected by the health condition of patients, we characterized the SVF cells of 30 lipedema patients in comparison to 22 healthy patients. METHODS: SVF cells were analyzed regarding cell yield, viability, adenosine triphosphate content, colony forming units and proliferative capacity, as well as surface marker profile and differentiation potential in vitro. RESULTS: Our results demonstrated a significantly enhanced SVF cell yield isolated from lipedema compared with healthy patients. In contrast, the adipogenic differentiation potential of SVF cells isolated from lipedema patients was significantly reduced compared with healthy patients. Interestingly, expression of the mesenchymal marker CD90 and the endothelial/pericytic marker CD146 was significantly enhanced when isolated from lipedema patients. DISCUSSION: The enhanced number of CD90(+) and CD146(+) cells could explain the increased cell yield because the other tested surface marker were not reduced in lipedema patients. Because the cellular mechanism and composition in lipedema is largely unknown, our findings might contribute to a better understanding of its etiology.

The present, revised guidelines on lipedema were developed under the auspices of and funded by the German Society of Phlebology (DGP). The recommendations are based on a systematic literature search and the consensus of eight medical societies and working groups. The guidelines contain recommendations with respect to diagnosis and management of lipedema. The diagnosis is established on the basis of medical history and clinical findings. Characteristically, there is a localized, symmetrical increase in subcutaneous adipose tissue in arms and legs that is in marked disproportion to the trunk. Other findings include edema, easy bruising, and increased tenderness. Further diagnostic tests are usually reserved for special cases that require additional workup. Lipedema is a chronic, progressive disorder marked by the individual variability and unpredictability of its clinical course. Treatment consists of four therapeutic mainstays that should be combined as necessary and address current clinical symptoms: complex physical therapy (manual lymphatic drainage, compression therapy, exercise therapy, and skin care), liposuction and plastic surgery, diet, and physical activity, as well as psychotherapy if necessary. Surgical procedures are indicated if - despite thorough conservative treatment - symptoms persist, or if there is progression of clinical findings and/or symptoms. If present, morbid obesity should be therapeutically addressed prior to liposuction.

Lymphedema is a chronic, progressive, and common but often unrecognized condition. The diagnosis of lymphatic disease on clinical grounds alone remains a challenge. Without proper diagnosis, therapy is often delayed, allowing disease progression. There is a need for a practical diagnostic algorithm and its imaging technique to guide clinical decision-making. The aim of this topical review is to provide a practical approach for assessing patients with suspected lymphedema and to give a critical appraisal of currently available imaging modalities that are applied in clinical practice to diagnose and map lymphatic disease.

Das Lipödem ist eine sehr komplexe, unvermutet häufig anzutreffende Erkrankung des Fettsystems der Extremitäten. Es handelt sich hier um ein lymphologisches Krankheitsbild, wobei besonders das Baufett betroffen ist. Nur in wenigen Fällen ist es auch mit metabolischen Symptomen assoziiert. Das Lipödem ist eine Sonderform der Adipositas, die weder in der Medizin noch in der Bevölkerung als bewegungs- und diätresistent wahrgenommen wird. Die betroffenen Patienten sind in ihrem seelischen Gleichgewicht äußerst betroffen. Aufgrund unserer anatomischen Untersuchungen kann man durchaus von einer ernsthaften, progressiven Erkrankung des subkutanen Fettgewebes und der benachbarten, assoziierten Strukturen sprechen. Es ist nicht nur die Klinik, sondern auch die duplexsonographische Evaluierung und impedanzanalytische Exploration sind zur Diagnosefindung und zur postoperativen Verlaufskontrolle notwendig. Auch bestätigt ein besonderes Verhalten der Stammzellen den Pathomechanismus. Durch Ausdünnung der Dermis und Verlust der elastischen Fasern sind dermatologische Problemstellungen wie Trockenheit, Infektneigung, Vulnerabilität und Neigung zu Ekchymosen erklärbar. Hier dürfte v. a. die Funktion des dermalen Fettes beeinträchtigt sein. Aus unseren Beobachtungen geht hervor, dass insbesondere die frühzeitige operative Therapie mittels Liposuktion einen nachhaltigen Wert für Patienten im Frühstadium hat und den Patienten eine deutliche Verbesserung der Lebensqualität bringt.

This study aimed to explore patients' perceptions regarding the impact that lower limb chronic oedema has on their quality of life (QoL). A quantitative descriptive design was used to collect data from patients with lower limb chronic oedema. A condition-specific validated questionnaire was distributed to a purposive sample (n = 122) through manual lymphatic drainage/vascular/health clinics in Ireland. Results indicated that patients with lower limb chronic oedema experience a wide range of physical problems such as limb heaviness (74%, n = 66), weakness (44%, n = 40) and pain (38%, n = 34). Additionally, difficulties with walking (53%, n = 48), standing (51%, n = 46) and bending (45%, n = 40) were reported. Concerns regarding poor body image were strongly evident (76%, n = 68). Difficulties finding clothing/footwear to fit oedematous limb(s) were reported (59%, n = 53), in addition to finding clothes that participants would like to wear (64%, n = 58). Emotional symptoms of irritability (42%, n = 38), anxiety (41%, n = 37) and tension (40%, n = 36) were reported. Over half of the participants (55%, n = 49) stated that their chronic swelling affected their social functioning and their ability to engage in leisure activities. This study has identified that lower limb chronic oedema has significant psychological, social and physical implications for persons' QoL.

An audit of 100 new patients attending a specialist lymphoedema clinic revealed 52% presented with chronic oedema. More than half (58%) of the chronic oedema group presented with skin changes whereas 14% of those with lipoedema, 4% with lymphoedema of the arm, and 8% with lymphoedema of the leg developed skin changes. None of the primary lymphoedema group developed skin changes. Chronic venous disease (CVD) was significantly more prevalent in the chronic oedema group. More patients with bilateral chronic oedema suffered from cellulitis (41%) compared to unilateral (27%). Skin changes, CVD and red leg syndrome (RLS) also occur more often in bilateral leg swelling. Incidence of cellulitis is highest in the chronic oedema group (36.5%), closely followed by the primary lymphoedema group (33.3%). 85% of the patients who were weighed (n=93) were overweight, 39% obese, and 29% morbidly obese. The findings from this audit highlight the importance of skin care training for community nurses managing chronic oedema patients.

Lymphedema is a complex and burdensome medical problem and requires continuous specific therapy. The aim of this cross-sectional study of community lymphedema care in the metropolitan area of Hamburg, Germany, was to evaluate health-related quality of life (QoL) in lymphedema patients. Generic as well as disease-specific health-related QoL was assessed using EQ-5D and FLQA-LK, respectively. Pain was assessed using a visual analogue scale (VAS). About 301 patients (median age of 60.5 years, 90.8% female) with lymphedema of any origin were included. About 66.4% had lymphedema, 24.1% combined lipolymphedema, and 9.5% lipoedema. Mean disease-specific QoL (FLQA-LK) was 2.4 (range 0 = no to 4 = maximum burden). The highest impairment values were observed in subscales for physical complaints, everyday life, and emotional well-being. Mean EQ-5D VAS was 70.4, mean EQ-5D score 63.3. Lymphedema was associated with major impairments in QoL, which differed for subgroups of pain, clinical severity, and comorbidity. Pain as a common problem for lymphedema patients seemed to be underestimated and undertreated. Early diagnosis and structured treatment strategies are urgently needed.

Introduction Lipedema is a chronic, progressive condition that can result in considerable disability. In 2011, the Dutch Society of Dermatology and Venereology organized a task force to create guidelines on lipedema, using the International Classification of Functioning, Disability and Health of the World Health Organization. Guideline development Clinical questions on significant issues in lipedema care were proposed, involving (1) making the diagnosis of lipedema; (2) clinimetric measurements for early detection and adequate follow-up; and (3) treatment. A systematic review of literature published up to June 2013 was conducted. Based on available evidence and experience of the task force, answers were formed and recommendations were stated. The guidelines define criteria to make a medical diagnosis of lipedema, a minimum data set of (repeated) clinical measurements that should be used to ensure early detection and an individually outlined follow-up plan, pillars on which conservative treatment should be based and recommendations on surgical treatment options. Conclusions Little consistent information concerning either diagnostics or therapy can be found in the literature. It is likely that lipedema is frequently misdiagnosed or wrongly diagnosed as only an aesthetic problem and therefore under- or mis-treated. Treatment is divided into conservative and chirurgic treatment. The only available technique to correct the abnormal adipose tissue is surgery. Recommendations To ensure early detection and an individually outlined follow-up, the committee advises the use of a minimum data set of (repeated) measurements of waist circumference, circumference of involved limbs, body mass index and scoring of the level of daily practice and psychosocial distress. Promotion of a healthy lifestyle with individually adjusted weight control measures, graded activity training programs, edema reduction, and other supportive measures are pillars of conservative therapy. Tumescent liposuction is the treatment of choice for patients with a suitable health profile and/or inadequate response to conservative and supportive measures.

Background: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD)., Methods and Results: Measurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T1-weighted and T2-weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately following MLD. Normative control and BCRL T2 values were quantified and a signed Wilcoxon Rank-Sum test was applied (significance: two-sided p < 0.05). Non-MRI measures yielded significant capacity for discriminating between arms with versus without clinical signs of BCRL, yet yielded no change in response to MLD. Alternatively, a significant increase in deep tissue T2 on the involved (pre T2 = 0.0371 ± 0.003 seconds; post T2 = 0.0389 ± 0.003; p = 0.029) and contralateral (pre T2 = 0.0365 ± 0.002; post T2 = 0.0395 ± 0.002; p < 0.01) arms was observed. Trends for larger T2 increases on the involved side after MLD in patients with stage 2 BCRL relative to earlier stages 0 and 1 BCRL were observed, consistent with tissue composition changes in later stages of BCRL manifesting as breakdown of fibrotic tissue after MLD in the involved arm. Contrast consistent with relocation of fluid to the contralateral quadrant was observed in all stages., Conclusion: Quantitative deep tissue T2 MRI values yielded significant changes following MLD treatment, whereas non-MRI measurements did not vary. These findings highlight that internal imaging measures of tissue composition may be useful for evaluating how current and emerging therapies impact tissue function.

BACKGROUND: People with lipedema or Dercum's disease (DD) can have a similar distribution of excess painful nodular subcutaneous adipose tissue (SAT), making them difficult to differentiate. METHODS: Case series of 94 patients with DD, 160 with lipedema and 18 with both diagnoses (Lip+DD) from a single clinic in an academic medical center to improve identification and differentiation of these disorders by comparison of clinical findings, prevalence of type 2 diabetes (DM2), hypermobility by the Beighton score and assessment of a marker of inflammation, Total complement activity (CH50). RESULTS: Differences between groups were by Student's t-test with α of 0.05. The Lipedema Group had significantly greater weight, body mass index (BMI), gynoid distributed nodular SAT and fibrotic and heavy tissue than the DD Group. Hypermobility was significantly higher in the Lipedema (58±0.5%) than DD Group (23±0.4%; P<0.0001). DM2 was significantly greater in the DD (16±0.2%; P=0.0007) than the Lipedema Group (6±0.2%). Average pain by an analog scale was significantly higher in the DD (6±2.5%) than the Lipedema Group (4±2.1%; P<0.0001). Fatigue and swelling were common in both groups. Easy bruising was more common in the Lipedema Group, whereas abdominal pain, shortness of breath, fibromyalgia, migraines and lipomas were more prevalent in the DD Group. The percentage of patients with elevated CH50 was significantly positive in both groups. CONCLUSIONS: The significantly lower prevalence of DM2 in people with lipedema compared with DD may be due to the greater amount of gynoid fat known to be protective against metabolic disorders. The high percentage of hypermobility in lipedema patients indicates that it may be a comorbid condition. The location of fat, high average daily pain, presence of lipomas and comorbid painful disorders in DD patients may help differentiate from lipedema.

The lymphatic system regulates tissue fluid homeostasis, intestinal fat absorption, and immune cell trafficing. Lymphedema is soft tissue swelling secondary to lymphatic dysfunction, which results in the accumulation of tissue fluid in the interstitial space. This might occur as a primary disorder of the developing lymphatic system, or alternatively lymphedema might be an acquired disorder secondary to lymphatic injury. For example, secondary lymphedema is a common problem following cancer and cancer treatments such as lymph node surgery and radiotherapy, resulting in significant morbidity. Radiotherapy is an established risk factor for lymphedema, and in addition to causing direct injury to the lymphatic vessel, it is possible that alternative mechanisms might also contribute to radiation-induced lymphatic dysfunction, such as localized ischemia of the lymphatic wall. It is also likely that predisposing genetic risk factors are at play, as not all individuals exposed to the same risk factors will develop secondary lymphedema. Lipoedema is a different form of soft tissue swelling due to the abnormal accumulation of adipose tissue. Lipoedema and lymphatic dysfunction appear to be linked, as individuals frequently develop a degree of lymphedema, particularly as the condition progresses in severity, where it may be decribed as lipo-lymphedema. The cause of lipoedema and the genetic basis of the condition are currently unknown. This thesis aims to discover and define alternative mechanisms for lymphtic dysfunction in the context of secondary lymphedema, particularly focussing on the supply of oxygenated blood to the lymphatic vessel wall. We also aim to describe inheritance patterns and the genetic factors involved in lipoedema and lipo-lymphedema. Such knowledge might uncover therapeutic targets and facilitate the development of treatments for lymphedema and lipoedema, including gene therapy.

Das Lipödem ist gekennzeichnet durch eine dispropor tionale Vermehrung des subkutanen Fettgewebes an Hüf ten, Beinen und Armen. Von der asymptomatischen Lipo hypertrophie unterscheidet es sich durch das Vorhandensein der typischen Symptome (Spontan und Berührungsempfindlichkeit, Ödeme). Auch wenn die Pathogenese des Lipödems immer noch weitgehend unbe kannt ist, deutet vieles darauf hin, dass neben hormonel len Faktoren entzündliche Prozesse eine wesentliche Rolle spielen. Dabei ist nicht geklärt, ob und in welcher Weise diese selbst ursächlich für das Auftreten des Lipödems sind oder Folge anderer körperlicher Veränderungen wie Adipositas oder hormoneller Dysbalancen. Der Circulus vitiosus aus Adipositas, die bei über der Hälfte der Patientinnen vorliegt, und der sich hierdurch entwickelnden Hyperinsulinämie bewirkt nicht nur eine weitere Fettgewebszunahme, sondern wirkt über die Zyto kine des viszeralen Fettgewebes auch proinflammatorisch und ödemfördernd,

EXECUTIVE SUMMARY Lipedema is a chronic condition that occurs almost exclusively in women and manifests as symmetrical buildup of painful fat and swelling in the limbs, sparing the hands and feet. A critical issue is the poorly understood disease biology, which for diagnosed patients results in limited treatment options that, at best, ameliorate the symptoms of lipedema. Individuals who suffer from the disease are further impacted by the absence of diagnostic tools, the lack of public and medical awareness of lipedema, and the stigma associated with weight gain. As a result, the true number of women with lipedema, or its epidemiology, is unknown. Braving these challenges is an active, numerous, and engaged patient community eager to participate in lipedema research. Supported by equally devoted caregivers and researchers, the lipedema field presents an immense opportunity for scientific and medical advancements. To capitalize on this potential, the Lipedema Foundation and the Milken Institute’s Center for Strategic Philanthropy convened leading stakeholders to discuss the current state of lipedema science and identify the key philanthropic research opportunities to advance the field. Little is known about how and why lipedema develops in a patient. Although the disease is reported to occur during puberty and other periods of hormonal changes, why this happens is not understood. The painful fat and swelling in some patients can be so debilitating that their mobility is impaired; yet what drives these symptoms is unknown. Psychosocial issues are also prevalent in women with lipedema, contributing to health burden and complexity of disease management. Furthermore, many patients develop the disease alongside obesity; however, diet, exercise, and weight loss surgery have limited effect on lipedema fat. Although the lack of disease biology is staggering, philanthropic investments in research can leverage the desire of patients to participate in studies to improve their and the entire field’s understanding of lipedema. The convergence of multiple scientific topics around lipedema indicates that addressing these gaps in research will also improve the understanding of hormone, pain and edema, mental health, and metabolic biology. There are no diagnostic tools or tests for lipedema. Diagnosis of lipedema involves a clinical assessment and discussion of the individual’s medical history, a process that is difficult to scale within the current healthcare system. The absence of diagnostic tools to streamline or confirm a clinical diagnosis is a key unmet need, which if addressed by philanthropy, has the potential to dramatically change the trajectory of the disease. Investing in research efforts to advance novel imaging technologies to diagnose lipedema is a promising research avenue that would simultaneously benefit individuals who suffer from the disease and healthcare providers unfamiliar with the condition. The public and medical community are not aware of lipedema. Lipedema was initially described in 1940, yet little knowledge about the disease has permeated the general public, with a concomitant lack of mention in the educational curriculum of medical trainees. Addressing this challenge will require philanthropic efforts to define the disease from a basic, clinical, and diagnostic perspective. A key philanthropic opportunity is support for a lipedema patient registry linked to a tissue biorepository. This effort has the potential to generate and support the needed disease research, while engaging patients as partners in understanding the science of lipedema.