Search

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.

Lower extremity edema is extremely common among patients seen across multiple specialties. The differential diagnosis is broad and ranges from simple dependent edema to more complex conditions such as chronic venous disease and lymphedema. Several key features from the history and physical exam can assist with the diagnosis. Imaging is rarely necessary at the initial visit unless venous thromboembolism is suspected. Treatment is specific to the etiology of the edema, but compression stockings, elevation, exercise, and weight loss remain the cornerstone in most cases.

Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, impairs lymphatic development. LECs use fatty acid β-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid β-oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 to acetylate histones at lymphangiogenic genes. PROX1-p300 interaction facilitates preferential histone acetylation at PROX1-target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. Notably, blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl coenzyme A by supplementing acetate rescues this process in vivo.

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.

Eat to starve lymphedema and lipedema by having foods that fight these conditions (and cancer) and avoiding foods that contribute to symptoms or related conditions. Learn how food choices affect both conditions and how better nutrition can improve symptoms (including pain) and delay changes associated with progression to more advanced stages. Intended for anyone with, or at risk for, lymphedema or lipedema, caregivers, lymphedema therapists, and other health care providers. Signs of lymphedema and lipedema (painful fat syndrome) include swelling (edema), abnormal fat accumulation, pain, skin changes, and infections (cellulitis, wounds or ulcers) in affected areas. Lymphedema and lipedema are progressive conditions that can be depressing, disfiguring, disabling, and (potentially) deadly, without treatment. This guide explains why nutrition is an essential part of treatment and self-care for these conditions, what to eat, and how to change your eating pattern. It also covers vitamins, minerals, and supplements that may be beneficial. You may be at risk for lymphedema if you have chronic venous insufficiency, other venous disorders, heart disease, obesity, a cancer diagnosis (especially breast cancer, reproductive system cancers, or melanoma), or a family history of lymphedema or swollen legs. Eating wisely and maintaining a healthy body weight can help reduce your risk of developing lymphedema symptoms

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.

Lipedema is a disproportional obesity featuring spontaneous or light pressure-induce pain and frequent hematoma formation due to even minor traumatic injuries. It is generally distinguished from general obesity primarily based on clinical hallmarks; however, this becomes difficult when appearing in a concomitant form (combination of obesity and lipedema). Our study group has recently demonstrated that lipedema-associated bruising is correlated with increased capillary fragility (CF) and also that CF could be significantly improved by complex decongestive physiotherapy (CDP). In this study, we measured CF in female subjects with lipedema (15) or non-complicated obesity (15) who were body mass index (BMI) and waist-to-hip ratio (WHR) matched. CF was evaluated with the vacuum suction method (VSM) using Parrot's angiosterrometer in both groups. Application of VSM resulted in a significantly higher number of petechiae in subjects with lipedema. Capillary fragility measurement appears to be a useful differential diagnostic tool between lipedema and obesity under these trial parameters.

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

The invention provides carbazole derivatives for the treatment of fibrotic diseases (pathological collagen deposition) in tissues and organs, and related symptoms, and conditions thereof.