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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.

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.

Lipedema an often overlooked but treatable disease Lipedema is a painful disease that affects some women between puberty and menopause through a subcutaneous fat accumulation especially in the lower extremities. Patients suffer from pain and pressure tenderness. The larger fat accumulation, especially on the inside of the thighs and knees, causes walking difficulties. This can successfully be treated by liposuction with good long-term results in terms of pain reduction and prevention of osteoarthritis development in the knee and ankle joints.

Lipoedema is a disorder of adipose tissue that occurs almost exclusively in women; the pathophysiology and aetiology are yet not well understood (Wold et al, 1951; Child et al, 2010; Fife et al, 2010). The condition was originally described in 1943 by Allen and Hines (Wold et al, 1951). The exact prevalence of lipoedema in women is unknown; its presence in the general female population has been estimated at 11% (Földi and Földi, 2012). It is a chronic, progressive condition that is associated with considerable morbidity, including discomfort, easy bruising and tenderness of the disproportionately enlarged legs, which may progress to highintensity pain and limited mobility, along planus, and complaints about general fatigue and physical impairment are often observed. In later stages, body mass index (BMI) ≥30 kg/m2 (obesity) may also develop. Clinical characteristics of lipoedema include swelling and symmetrical enlargement of the lower limbs due to abnormal deposition of subcutaneous fat, with a sharp transition area of affected to unaffected tissue occasionally accompanied by over-hanging lipoedema tissue (Box 1). This is recognised as the typical ‘cuff-sign’, also called as ‘inverse shouldering’ or the ‘bracelet effect’. Lipoedema often co-exists with obesity, and obesity may be misdiagnosed, although Abstract

Lipoedema is a chronic progressive adipose disorder that affects mainly women and presents as symmetrical enlargement of the buttocks and legs. It is commonly misdiagnosed as obesity or lymphoedema, but careful assessment will reveal a disproportionate enlargement below the waist which is resistant to dieting, sparing of the feet, legs are tender or painful to touch and bruise easily, there is occasional orthostatic oedema, and there is often significant psychological morbidity. Lipoedema is a oestrogen-regulated condition with onset around puberty in 78% of women, and there is often a strong family history. The condition is exacerbated by weight gain and there is increasing anecdotal evidence that women who are obese are seeking a diagnosis of lipoedema, either to procure NHS funded manual lymphatic drainage, or to medicalise their obesity and avoid acknowledging that the responsibility for their weight gain is lifestyle orientated. Management of lipoedema consists of accurate diagnosis, psychological care, management of orthostatic oedema, and prevention of progression through skin care and weight management.

Lipedema, or adiposis dolorosa, is a common adipose tissue disorder that is believed to affect nearly 11% of adult women worldwide. It is characterized most commonly by disproportionate adipocyte hypertrophy of the lower extremities, significant tenderness to palpation, and a failure to respond to extreme weight loss modalities. Women with lipedema report a rapid growth of the lipedema subcutaneous adipose tissue in the setting of stress, surgery, and/or hormonal changes. Women with later stages of lipedema have a classic "column leg" appearance, with masses of nodular fat, easy bruising, and pain. Despite this relatively common disease, there are few physicians who are aware of it. As a result, patients are often misdiagnosed with lifestyle-induced obesity, and/or lymphedema, and subjected to unnecessary medical interventions and fat-shaming. Diagnosis is largely clinical and based on criteria initially established in 1951. Treatment of lipedema is effective and includes lymphatic support, such as complete decongestive therapy, and specialized suction lipectomy to spare injury to lymphatic channels and remove the diseased lipedema fat. With an incidence that may affect nearly 1 in 9 adult women, it is important to generate appropriate awareness, conduct additional research, and identify better diagnostic and treatment modalities for lipedema so these women can obtain the care that they need and deserve.

Lipoedema is a long-term, progressive condition, usually presenting as symmetrical enlargement of the legs and buttocks, and mainly affecting women. Distinct from obesity or lymphoedema, lipoedema is associated with an unusual distribution and proliferation of diet-resistant inflammatory fat tissue. This article provides background to lipoedema diagnosis and discusses self-care support for women with lipoedema.

Compression therapy is a key component in the effective management of people with lower limb problems associated with venous, lymphatic and fat disorders such as lipoedema. Individuals with lymphoedema, venous ulceration and lipoedema often require long-term compression therapy to prevent and manage problems such as chronic ulceration and skin changes, persistent swelling and shape distortion. Challenges remain in achieving acceptable, safe, effective and cost-efficient compression therapy choices. Adjustable compression wrap devices using hook and loop fasteners, commonly called VELCRO brand fasteners, present new opportunities for improving treatment outcomes, supporting patient independence and self-management in the use of compression therapy. This paper reports the findings of an evidence review of adjustable compression wrap devices in people with lymphoedema, chronic oedema, venous ulceration and lipoedema. DECLARATION OF INTEREST: The authors have no conflict of interest to declare.

While there is no proven cure for lipoedema, early detection is key as specialist treatments, complemented by self-management techniques, can improve symptoms and prevent progression. There is no universal approach as the correct treatment or treatments will depend on each patient's particular circumstances; however, when chosen early and appropriately, interventions can provide huge benefits. The most common treatments in the management of lipoedema include compression, manual lymphatic drainage (MLD), tumescent liposuction, intermittent pneumatic compression therapy (IPC), kinesio taping, deep oscillation therapy, and cognitive behavioural therapy (CBT).

Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g. , magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention.

Lymphoscintigraphy has emerged as the diagnostic test of choice differentiating lymphoedema from other causes of extremity swelling in adult and paediatric patients with a high clinical suspicion of impaired lymphatic function. In paediatric patients who present with lymphoedema, primary lymphoedema accounts for the majority of the cases, with prevalence estimates that approximate 1.15/100,000 persons aged less than 20 years. Other causes of lymphoedema include combined lymphatic vascular diseases and to a lesser extent, secondary lymphoedema due to surgical and non-surgical trauma to the lymphatic system. Lymphoscintigraphy plays an important role in the direction of clinical management in these patients with lymphoedema and proper recognition of lymphoscintigraphic patterns in this population is essential. Sentinel lymph node localization and biopsy has become standard of care in adult patients with melanoma and breast cancer. It is recommended in paediatric and adolescent patients with melanoma, peripheral rhabdomyosarcomas, and several specific soft tissue sarcomas.

Lipedema is an uncommon disorder characterized by localized adiposity of the lower extremities, often occurring in females with a family history of the condition. The adiposity extends from hips to ankles and is typically unresponsive to weight loss. In addition to the aesthetic deformity, women also describe pain in the lower extremities, particularly with pressure, as well as easy bruising. Although the condition is well described, it is relatively rare and often misdiagnosed. The purpose of this review is to describe the initial evaluation and diagnosis of lipedema and discuss treatment options.

At present, there is no proven cure for lipoedema. Nevertheless, much can be done to help improve symptoms and prevent progression. Many of these improvements can be achieved by patients using self-management techniques. This article describes the range of self-management techniques that community nurses can discuss with patients, including healthy eating, low-impact exercise, compression garments, self-lymphatic drainage, and counselling.

Lipedema is a disorder of adipose tissue that primarily affects females and is often misdiagnosed as obesity or lymphedema. Relatively few studies have defined the precise pathogenesis, epidemiology, and management strategies for this disorder, yet the need to successfully identify this disorder as a unique entity has important implications for proper treatment. In this review, we sought to review and identify information in the existing literature with respect to the epidemiology, pathogenesis, clinical presentation, differential diagnosis, and management strategies for lipedema. The current literature suggests that lipedema appears to be a clinical entity thought to be related to both genetic factors and fat distribution. While distinct from lymphedema and obesity, there are some existing treatments such as complex decongestive physiotherapy, liposuction, and laser-assisted lipolysis. Management of lipedema is complex and distinct from lymphedema. The role of newer randomized controlled studies to further explore the management of this clinical entity remains promising.

Lipedema is a poorly understood clinical entity that is frequently under-diagnosed and neglected or else confused with lymphoedema. However, in most cases, diagnosis is simple and does not usually necessitate laboratory examinations. There is an extremely high demand for therapy since the condition causes major morbidity and affects quality of life. The aim of treatment is to reduce patient weight; although weight loss does not affect the morphology of the lower limbs, it optimises patient mobility while reducing related complaints and improving quality of life. Conservative surgical measures, of which tumescent liposuction is the most frequent, provide improvement of certain symptoms. A better understanding of this entity will result in improved therapy.