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

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

Lipoedema used to be a rather unknown disease. In the past five years, it has gained increasing awareness, especially through media attention. Besides non-surgical treatment by complex conservative decongestion, there are an increasing number of studies pointing out the potential of liposuction for a successful treatment of lipoedema. As a result, an increasing number of affected patients present to plastic surgeons and request correction and pain relief.As the German Federal Joint Committee (Gemeinsamer Bundesausschuss (G-BA)) has not positively acknowledged liposuction as a treatment for lipoedema so far, coverage of the procedure by the statutory health insurance is still a decision on a by-case basis. Therefore, patients seeking liposuction treatment must apply for prior cost approval from the statutory health insurance in cooperation with their plastic surgeon. The review at hand provides a summary of the current prevailing legal norms and gives advice on how to apply for prior cost approval.

In case of an acute leg swelling a deep leg vein thrombosis needs to be excluded. In order to do this, compression sonography and the D-dimer-test are applied in the framework of an established diagnostic algorithm. The ensuing therapy consists in anticoagulation and compression.In case of a chronic leg swelling anamnesis and a clinical check-up often lead to a differential diagnosis. Chronic venous insufficiency is a generic term for a disturbed venous backflow. It is caused by an obstruction or an antegrade or retrograde flow insufficiency. Most common diseases in this context are varicosis or a post-thrombotic syndrome. Sonography and special function tests provide a diagnosis. The basic therapy consists in regular exercise, normalization of weight and compression therapy. In case of a hemodynamically relevant varicose vein surgery or endovascular treatment is advisable. The post-thrombotic syndrome must be treated consistently with the basic therapy.A lymphedema may be hereditary or acquired. In a first step diseases like neoplasia need to be excluded. The initial therapy consists in manual lymph drainage in combination with special compression bandages. Flat knit stockings should be prescribed. Surgical treatment is reserved for special circumstances.A lipedema is clinically diagnosed. It is characterized by lipohypertrophia, pressure sensitivity of the tissue and susceptibility to hematomas. Treatment options include weight reduction, regular exercise, lymph drainage and compression therapy, in some cases liposuction.

Lipedema is a chronic disabilitating disease affecting the subcutaneous adipose tissue of the extremities in females during or after puberty. The disease is characterized by bilateral swelling of legs and/or arms, bruising, and pain. In contrast to lymphedema, the most distal parts remain unaffected. In contrast to obesity, patients with lipedema have a lower risk of diabetes mellitus. The pathogenesis is not well understood. However, hormonal factors seem to play a vital role, as it is an exclusively female disorder. The recent advantages in understanding and treating lipedema are reviewed.

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

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

<p>Um das Lipödem ranken sich zahlreiche Mythen! In diesem vierten Beitrag unserer Artikelserie setzen wir uns mit dem Stellenwert der Liposuktion beim Lipödem auseinander. Wir diskutieren das von vielen die Liposuktion durchführenden Ärzten verbreitete Statement: „Die Liposuktion führt zu ausgeprägter und dauerhafter Verbesserung des Lipödems“. Wir konnten zeigen, dass zwischen den oft euphorischen Versprechungen der chirurgisch tätigen Kollegen und der aktuellen Studienlage zur Liposuktion eine erhebliche Lücke klafft. Sowohl Studienqualität als auch Studiensetting weisen erhebliche Mängel auf, Mängel, die Zweifel an diesem verbreiteten Statement aufkommen lassen. Eine ähnliche Lücke klafft darüber hinaus zwischen den Empfehlungen der S1-Leitlinie Lipödem und der tatsächlichen „Absaugpraxis“ bei adipösen Lipödempatientinnen. Die in den Leitlinien empfohlene „kritische Indikationsstellung“ bei gleichzeitigem Auftreten von Lipödem und Adipositas findet kaum Gehör. Es kann daher nicht genug betont werden, dass Liposuktion keine Methode ist, um Adipositas zu behandeln. Gleichwohl kann die Liposuktion durchaus zu einer Verbesserung des Lipödems beitragen. Entscheidend für den Therapieerfolg ist die Auswahl der Patientinnen, die aufgrund – medizinischer – Kriterien erfolgen muss. Darüber sollte die Liposuktion in ein Gesamtkonzept eingebunden werden, welches psychosoziale, ernährungs- und sportmedizinische Gesichtspunkte berücksichtigt.</p>

Methemoglobinemia is characterized by an increased level of methemoglobin (MetHb) in the peripheral blood. MetHb levels increase after tumescent anesthesia and need to be monitored. If a patient becomes symptomatic and/or the MetHb levels increase >10%, intravenous injection of an antidote is recommended. Toluidine blue is twice as effective as methylene blue in this respect.A 27-year-old woman with advanced lipedema underwent her third liposuction under tumescent anesthesia. After surgery, her MetHb levels increased and needed injection of toluidine blue. She developed an acute and painful edema after extravasation of some toluidine blue due to a bursting vein. This is the first report in the recent medical literature. Clinical presentation, course, and treatment are described.

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

Advanced lymphedema is associated with a number of adverse skin changes including color, thickening of the epidermis, dryness, and hyperkeratosis. These changes are related to prolonged lymph stasis and contribute to an increased risk of infection. Similarly, lipedema is associated with skin thickening and appearance of nodular adipose deposition. Skin care is essential in both conditions. We examined whether inclusion of targeted skin products for 2 weeks to an established pre-surgical conservative treatment program was associated with beneficial effects on the skin condition in 150 patients with lymphedema and lipedema. Patients were randomly assigned to control or one of two treatment groups. All three groups (and for both lymphedema and lipedema) demonstrated a significant reduction in softness. Dimpling/ redness was significantly reduced in the targeted skin product groups for both patients with lymphedema or lipedema. Only patients with lipedema demonstrated a significant reduction in dryness/ hyperkeratosis following targeted skin product treatment. This study demonstrates that short-term use of targeted skin products in both patients with lymphedema and lipedema can be of benefit and further studies are needed to replicate these results and explore possible mechanisms.

Lipedema is a chronic fat disorder with disproportional fat distribution, especially around the legs, hips, and sometimes arms, and it affects women almost exclusively. The major symptoms and complaints include pain in the soft tissue and the feeling of “heavy legs.” The perception of pain depends to a high degree on the psychological condition of the patient. Obesity is the major comorbidity and can worsen lipedema. In combination with impaired levels of physical activity, there is an increase in interstitial filtration, and noninfectious inflammation with capillary leakage can occur. Eventually, chronic edema develops due to the dynamic insufficiency of the lymphatic system. However, edema is not a pathognomonic aspect of lipedema. There are many controversies and myths about the condition lipedema, and no objective diagnostic tool is available to confirm the diagnosis. Therapeutic approaches in lipedema are multimodal and focus on the biomedical, psychological, and functional aspects involved with the disorder. A lifestyle change is often part of the therapeutic program, along with other therapeutic interventions, such as exercise, compression, weight management, and nutritional and psychological support. Clinimetrics with validated techniques in all fields of human functioning of a lipedema patient are mandatory to objectively evaluate the improvements that are due to the treatment program. Liposuction is a technique to remove fat and is therefore introduced to treat lipedema. Some doctors who offer the procedure state that “liposuction leads to comprehensive and long-term improvements in lipedema and cures the disease.” These statements are often too optimistic and lead to high costs for the patient and disappointment in the end. However, liposuction can lead to improvements in lipedema when offered within a therapeutic program that includes other nonoperative modalities for the correct selection of patients according to their medical criteria. It cannot be emphasized enough that liposuction is not a method that should be used to treat obesity.

Subcutaneous adipose tissue diseases involving adipose tissue and its fascia, also known as adipofascial disorders, represent variations in the spectrum of obesity. The adipofascia diseases discussed in this chapter can be localized or generalized and include a common disorder primarily affecting women, lipedema, and four rare diseases, familial multiple lipomatosis, angiolipomatosis, Dercum disease, and multiple symmetric lipomatosis. The fat in adipofascial disorders is difficult to lose by standard weight loss approaches, including lifestyle (diet, exercise), pharmacologic therapy, and even bariatric surgery, due in part to tissue fibrosis. In the management of obesity, healthcare providers should be aware of this difficulty and be able to provide appropriate counseling and care of these conditions. Endocrinologists and primary care providers alike will encounter these conditions and should consider their occurrence during workup for bariatric surgery or hypothyroidism (lipedema) and in those that manifest, or are referred for, dyslipidemia or diabetes (Dercum disease). People with angiolipomas should be worked up for Cowden’s disease where a mutation in the gene PTEN increases their risk for thyroid and breast cancer. This chapter provides details on the pathophysiology, prevalence, genetics and treatments for these adipofascial disorders along with recommendations for the care of people with these diseases. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

Lymphedema has always been a neglected global health care problem. A central requirement for the development of any chronic disease is the clear use of public health definitions that can be used internationally to define populations. The term ‘‘lymphedema’’ has historically been defined as either primary, resulting from failure of lymphatic development, or secondary, following damage to the lymphatics (e.g., cancer treatment, injury, or filariasis). Attempts to integrate causes of edema arising from damage to the venous system or the effects of gravity, immobility, and systemic disease have rarely been integrated. More recently, the prominent role of the lymphatics in tissue fluid homeostasis in all forms of chronic edema has been recognized. These advances led to the development of the term: ‘‘Chronic edema: a broad term used to describe edema, which has been present for more than three months.’’ It can be considered an umbrella term that includes not only conventional ‘‘lymphedema’’ but also chronic swelling, which may have a more complex cause. This definition has been adapted in the international epidemiology study (LIMPRINT) that identified people throughout the health and social care systems in participating countries. Clearer definitions will allow for examination of this important public health problem that is likely to escalate given the projections of an aging population with multiple comorbidities. It will be possible to define both the hidden mortality and morbidity associated with complications, such as cellulitis and the impact on health-related quality of life. This evidence is urgently required to lobby for increased resource and effective health care in an increasingly competitive health care arena in which more established conditions have greater priority and funding.

Venous ulcers are chronic transcutaneous wounds common in the lower legs. They are resistant to healing and have a 78% chance of recurrence within 2 years. It is commonly accepted that venous ulcers are caused by the insufficiency of the calf muscle pump, leading to blood pooling in the lower legs, resulting in inflammation, skin oedema, tissue necrosis and eventually skin ulceration. However, the detailed physiological events by which inflammation contributes to wound formation are poorly understood. We therefore sought to develop a model that simulated the inflammation, using it to determine the internal stresses and pressure on the skin that contribute to venous ulcer formation. A three-layer finite-element skin model (epidermis, dermis and hypodermis) was developed to explore the roles in wound formation of two inflammation identifiers: glycosaminoglycans (GAG) and sodium. A series of parametric studies showed that increased GAG and sodium content led to oedema and increased tissue stresses of 1.5 MPa, which was within the reported range of skin tissue ultimate tensile stress (0.1–40 MPa). These results suggested that both the oedema and increased fluid pressure could reach a threshold for tissue damage and eventual ulcer formation. The models presented here provide insights to the pathological events associated with venous insufficiency, including inflammation, oedema and skin ulceration.

Obesity is a clinical condition that affects millions of people around the world and is associated with inflammatory processes. The aim of the present study was to report the association between obesity, lipedema, and systemic fluid retention, characterizing subclinical systemic lymphedema with aggravating factors. A 50-year-old female patient weighing 150 kilograms (body mass index: 60.2 kg/m2) reported being obese since childhood, but more located on the hips. She had a family history of this body configuration. Electrical bioimpedance analysis revealed generalized edema, constituting systemic lymphedema. Subclinical systemic lymphedema is caused by obesity and lipedema is also associated with this condition.