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Lipedema is a disease with unknown etiology presenting as bilateral and symmetric enlargement of the lower extremities due to subcutaneous deposition of the adipose tissue. Here we describe the histopathological features of the lipedema tissue and nonaffected adipose tissue obtained from a typical patient with severe lipedema. Immunohistochemical analyses indicated degenerative and regenerative changes of the lipedema tissue, characterized by crown-like structures (necrotizing adipocytes surrounded by infiltrating CD68+ macrophages; a feature commonly seen in obese adipose tissue) and proliferation of adipose-derived stem/progenitor/stromal cells (Ki67+CD34+ cells), respectively. These findings suggested increased adipogenesis in the lipedema tissue, which may further lead to hypoxia similar to that seen in obesity, resulting in adipocyte necrosis and macrophage recruitment. The confinement to the lower extremities and the difference from systemic obesity warrants further elucidation in future studies.

We report a familial Sotos syndrome in two children, boy and girl, aged 17 and 8 years, and in their 44 year old mother, who displayed normal intelligence at adult age, but suffered from insulin dependent diabetes mellitus, bronchial asthma, and severe lipedema. The underlying missense mutation, C2175S, occurred in a conserved segment of the NSD1 gene. Our findings confirm that familial cases of SS are more likely to carry missense mutations. This case report may prove useful to avoid underestimation of the recurrence rate of SS, and to demonstrate that the developmental delay may normalize, enabling an independent life and having an own family.

Einleitung: Bei einem Lipödem liegt eine anlagebedingte Fettgewebsvermehrung vor, bei der es zu einer symmetrischen Verdickung der Extremitäten kommt. Klinisch ist für das Lipödem eine Druckschmerzhaftigkeit charakteristisch. Bei länger bestehendem Lipödem kann man beobachten, dass bei einem Teil der Patientinnen zusätzliche Beschwerden auftreten. Die betroffenen Frauen erleben auf Grund der massiven Schwellungen dann, neben einem ausgeprägten Spannungs- und Schweregefühl der Beine, physische und psychische Belastungen, wodurch Sportangebote häufig nicht wahrgenommen werden und die soziale Interaktionen eingeschränkt ist. Studiendesign: Die vorliegende prospektive randomisierte Studie wurde zur Evaluation der Wirksamkeit eines vibrationsgestützten Krafttrainings mit dem Galileo-System im Vergleich zu einem herkömmlichen Training zur Aktivierung der Beinmuskelpumpe bei Patientinnen mit Lipödem durchgeführt. Die Probanden beider Gruppen erhielten 12 Anwendungen in einem Zeitraum von sechs Wochen. Zur Beurteilung des Therapieverlaufs wurde die Druckschmerzschwelle im Beinbereich mithilfe der visuellen Analogskala (VAS) und der Dolorimetrie an definierten Messpunkten erfasst. Nebenzielkriterien waren die Volumenreduktion und die Verbesserung funktioneller Parameter sowie der Lebensqualität. Die Erhebung der Outcomeparameter erfolgte vor der Intervention (U1), vor der letzen Trainingseinheit (U2) und 6 Wochen nach Therapieende (U3). Ergebnisse: Das Vibrationstraining (n=27) und die Venengymnastik (n=17) zeigten bezüglich der Schmerzlinderung signifikante Verbesserungen im Therapieverlauf. Die Druckschmerzschwelle konnte erhöht werden. Die Auswertung der Fragebögen zu Hämatomneigung und Schmerzempfinden ergab in der Interventionsgruppe eine signifikante Beschwerdelinderung im Therapieverlauf. In beiden Gruppen konnte eine subjektive Verbesserung der Mobilität und ein positiver Einfluss auf die Lebensstiländerung verzeichnet werden. Die im Gehtest beurteilte Ausdauerleistung verbesserte sich ebenfalls. Diskussion: Es konnte gezeigt werden, dass sowohl mit herkömmlicher Krankengymnastik als auch durch ein gerätegestütztes Vibrationstraining zwei wesentliche Symptome des Lipödems, nämlich Druckschmerzhaftigkeit und Hämatomneigung, positiv beeinflusst werden können. Somit lässt sich die Notwendigkeit unterstreichen, dass eine Therapie des Lipödems durch eine Bewegungstherapie ergänzt werden sollte.

OBJECTIVE: To evaluate methods to assess peripheral edema for reliability, feasibility and correlation with the classic clinical assessment of pitting edema. DESIGN: Cross-sectional observational study. SETTING: Large primary care clinic in Marshfield, Wisconsin, USA. PARTICIPANTS: Convenience sample of 20 patients with type 2 diabetes and a range of edema severity, including patients without edema. METHODS: Eight methods of edema assessment were evaluated: (1) clinical assessment of pit depth and recovery at three locations, (2) patient questionnaire, (3) ankle circumference, (4) figure-of-eight (ankle circumference using eight ankle/foot landmarks), (5) edema tester (plastic card with holes of varying size pressed to the ankle with a blood pressure cuff), (6) modified edema tester (edema tester with bumps), (7) indirect leg volume (by series of ankle/leg circumferences), and (8) foot/ankle volumetry by water displacement. Patients were evaluated independently by three nurse examiners. RESULTS: Water displacement and ankle circumference had high inter-examiner agreement (intraclass correlation coefficient 0.93, 0.96 right; 0.97, 0.97 left). Agreement was inconsistent for figure-of-eight (0.64, 0.86), moderate for indirect leg volume (0.53, 0.66), and low for clinical assessments at all locations. Agreement was low for the edema testers but varied by the pressure administered. Correlation with the classic, subjective clinical assessment was good for the nurse-performed assessments and patient questionnaire. Ankle circumference and patient questionnaires each took 1 minute to complete. Other tools took >5 minutes to complete. CONCLUSIONS: Water displacement and ankle circumference showed excellent reliability; however, water displacement is a time-consuming measure and may pose implementation challenges in the clinical and clinical trial environments. Patient-reported level and frequency of edema, based on an unvalidated questionnaire, was generally well correlated with the physician assessment of edema severity and may prove to be another reliable and accurate method of assessing edema. Additional study is needed to evaluate the validity and responsiveness of these methods.

OBJECTIVE: To assess for the first time the morphology of the lymphatic system in patients with lipedema and lipo-lymphedema of the lower extremities by MR lymphangiography. MATERIALS AND METHODS: 26 lower extremities in 13 consecutive patients (5 lipedema, 8 lipo-lymphedema) were examined by MR lymphangiography. 18 mL of gadoteridol and 1 mL of mepivacainhydrochloride 1% were subdivided into 10 portions and injected intracutaneously in the forefoot. MR imaging was performed with a 1.5-T system equipped with high-performance gradients. For MR lymphangiography, a 3D-spoiled gradient-echo sequence was used. For evaluation of the lymphedema a heavily T2-weighted 3D-TSE sequence was performed. RESULTS: In all 16 lower extremities (100%) with lipo-lymphedema, high signal intensity areas in the epifascial region could be detected on the 3D-TSE sequence. In the 16 examined lower extremities with lipo-lymphedema, 8 lower legs and 3 upper legs demonstrated enlarged lymphatic vessels up to a diameter of 3 mm. In two lower legs with lipo-lymphedema, an area of dermal back-flow was seen, indicating lymphatic outflow obstruction. In the 10 examined lower extremities with clinically pure lipedema, 4 lower legs and 2 upper legs demonstrated enlarged lymphatic vessels up to a diameter of 2 mm, indicating a subclinical status of lymphedema. In all examined extremities, the inguinal lymph nodes demonstrated a contrast material enhancement in the first image acquisition 15 min after injection. CONCLUSION: MR lymphangiography is a safe and accurate minimal-invasive imaging modality for the evaluation of the lymphatic circulation in patients with lipedema and lipo-lymphedema of the lower extremities. If the extent of lymphatic involvement is unclear at the initial clinical examination or requires a better definition for optimal therapeutic planning, MR lymphangiography is able to identify the anatomic and physiological derangements and to establish an objective baseline.

Lipoedema is a fat distribution disorder causing massive, bilaterally symmetrical enlargement of the lower and in some cases the upper extremities in women. The atraumatic, anatomically appropriate procedure of water jet-assisted liposuction available today represents a promising treatment for these patients who generally suffer from severe subjective and objective impairment. Liposuction treatment can bring long-term improvement if the operative technique focuses on lymph vessel preservation. Immunohistologic analyses show minimal evidence of lymph vessel structures in lipoaspirates. The histologic analysis of the aspirates documents a relatively specific removal ("apheresis") of primarily intact lipocytes with low vascular amount.

BACKGROUND Many surgeons consider liposuction using tumescent local anesthesia (TLA) to be a safe technique, but when TLA has been combined with other techniques, such as general anesthesia or intravenous medication, or when the guidelines associated with TLA have been violated, serious complications and deaths have occurred. This has resulted in uncertainty concerning the safety of liposuction using TLA, which this article seeks to resolve. OBJECTIVE To investigate whether liposuction using TLA is a safe procedure. METHODS The same surgeon performed liposuction using exclusively TLA in 3,240 procedures. Detailed records were kept of the complications that occurred. RESULTS In a series of 3,240 procedures, no deaths occurred, and no complications requiring hospitalization were experienced. In nine cases, complications developed that needed further action. CONCLUSIONS Liposuction using exclusively TLA is a proven safe procedure provided that the existing guidelines are meticulously followed.

Lipedema is a disproportional obesity featuring frequent hematoma formation due to even minor traumatic injuries. On the basis of clinical observations, complete decongestive physiotherapy diminishes the incidence of hematomas due to minor injuries beyond leg volume reduction. Hematoma development may be caused by altered capillary resistance (CR) or altered capillary fragility (CF). We measured capillary fragility (CF) before and after complex decongestive physiotherapy (CDP) to examine, whether CDP could reduce CF. 38 women with lipedema were included in the study. Twenty-one (21) patients were treated with CDP and 17 using exclusively moisturizers as the control group. CDP comprised once daily manual lymph drainage, intermittent pneumatic compression and multilayered short-stretch bandaging performed throughout a 5-day-course. CF was evaluated with the vacuum suction method (VSM) using Parrot's angiosterrometer in both groups. Decongestive therapy resulted in a significant reduction of the number of petechiae while no change was detected within the control group. Complete decongestive physiotherapy significantly reduced CF in patients with lipedema and this reduction may lead to reduced hematoma formation.

Lipedema is a disproportional obesity for which evidence-based treatment is not currently available. We studied whether complete decongestive physiotherapy (CDP) alone or combined with intermittent pneumatic compression (IPC) could improve the treatment outcome in women with lipedema using a prospective, randomized trial. Eleven patients received CDP (60 min) and thirteen CDP (30 min) plus IPC (30 min) once daily in a 5-day-course. Subsequent to drainage, all subjects received multilayered compression bandaging, physical exercise and skin care. Treatment efficacy was evaluated by limb volume reduction. Both groups achieved significant reductions in mean lower extremity volume (p < 0.05). The addition of IPC is safe, although it provides no synergistic benefit to CDP in leg volume reduction under these study conditions.

Introduction: Complaints of lipoedema are mainly referred to as pressure pain or tension in the scientific literature. Objective: The objective was to enable a further differentiation of the quality of the perceived discomfort and provide a preliminary quantification of pain severity. Methods: 50 patients with Stage II lipoedema were asked to complete a questionnaire containing 30 items corresponding to sensory and affective pain sensations. For these items, they could choose between “completely applicable”, “largely applicable”, “somewhat applicable”, or “not applicable”. The patients were also asked to describe their complaints in their own words. Results: The items pressing and dull were specified most frequently. The following were indicated to a lesser extent: severe, tearing, nagging, unnerving, fierce, unbearable, exhausting, and sharp. Compared to patients with chronic pain, the mean values of all the patients’ sensory and affective scores yielded an average pain severity. However, when the patients used their own formulations, the complaints were often described as being very pronounced. Conclusion: Only a small portion of the adjectives offered was suitable for characterising the sensations of lipoedema. There were considerable inter-individual variations in how the pain was perceived. The severe symptoms, which are partially subjective, should be considered when characterising lipoedema.

In 10 patients, lymphatic drainage was studied before and after liposuction of the legs, employing dynamic lymph scintigraphy. The data (comparison of right/left, stress/rest, before/after liposuction) were well reproducible. Lymphatic drainage was not altered significantly after liposuction as compared to the pretherapeutic status. Particularly, no relevant disturbance of lymphatic drainage became evident. Our limited data indicate that liposuction does not cause relevant damage to lymph vessels.

OBJECTIVE: Many investigations and treatments exist for lower limb lymphoedema. We undertook a survey on the management of this condition by vascular surgeons and the resources available for its treatment in the UK. DESIGN: A questionnaire was designed to assess the management of lymphoedema. MATERIALS AND METHOD: A postal questionnaire was sent to all members of the The Vascular Society of Great Britain and Ireland. RESULTS: 251/440 (57%) consultant surgeons returned a completed questionnaire comprising 45.3% teaching hospital and 54.7% district general hospital (DGH) consultants. 77.9% of the consultants saw less than 10 patients annually with lymphoedema. The commonest causes of lymphoedema were primary lymphoedema (99.3%) and malignancy (37.1%). Lipoedema, a cause of limb swelling was only seen or recognised by 46.2% of the consultants. The commonest investigations performed were a duplex scan, lymphoscintigram, full blood count and urea and electrolytes. The common methods of confirming lymphoedema were either by lymphoscintigram (54.5%) or from a diagnosis of exclusion (33.7%). Lymphoedema physiotherapy was available only to 53.8% of the consultants. Surgery was performed by 10.5% of consultants. 73.4% of the consultants believed that lymphoedema is managed inadequately and 72.9% believed that resources are insufficient in the UK for this condition. CONCLUSION: In the UK the majority of vascular consultants see less than 10 patients annually with lymphoedema. Very few patients undergo confirmation of this diagnosis with non-invasive investigation and very few consultants perform surgery. Management of this condition is perceived by the consultants to be poor, with a lack of resources and particular shortage of lymphoedema physiotherapists. Centralisation of these services may be a way of improving this condition.

BACKGROUND: Lipedema is a rare and painful disease in women. Until recently, it could be treated only by conservative methods (combined physical therapy). OBJECTIVE: To determine the efficacy and safety of surgery (liposuction) concerning appearance and associated complaints. METHODS: Twenty-eight patients, who had undergone conservative therapy over a period of years, were treated by liposuction under tumescent local anesthesia with vibrating microcannulas. Twenty-one could be reevaluated after an average of 12.2 (1-26) months. RESULTS: All showed great improvement, with normalization of body proportions. Additionally, spontaneous pain, sensitivity to pressure, and bruising either disappeared completely or improved markedly. Other than minor swelling for a few days, no complications could be observed following surgery. All patients reported a tremendous increase in their quality of life. Physical therapy had to be continued to a much lower degree. CONCLUSION: Tumescent liposuction has proved to be a safe and effective treatment for lipedema.

In vivo measurements in 26 female patients with lipedema and cellulite parameters were carried out before and after therapy by means of complex physical decongestive therapy (CPDT) including manual lymph drainage and compression as main components and/or shock wave therapy (SWT). Oxidative stress parameters of blood serum and biomechanic skin properties/smoothening of dermis and hypodermis surface were evaluated. Oxidative stress in lipedema and cellulite was demonstrated by increased serum concentrations of malondialdehyde (MDA) and plasma protein carbonyls compared with healthy control persons. Both MDA and protein carbonyls in blood plasma decreased after serial shock wave application and CPDT. The SWT itself and CPDT itself lead to MDA release from edematous tissue into the plasma. Obviously both therapy types, SWT and CPDT, mitigate oxidative stress in lipedema and cellulite. In parallel SWT improved significantly the biomechanic skin properties leading to smoothening of dermis and hypodermis surface. Significant correlation between MDA depletion of edematous and lipid enriched dermis and improvement of mechanic skin properties was demonstrated. From these findings it is concluded, that a release of lipid peroxidation (LPO) products from edematous dermis is an important sclerosis-preventing effect of SWT and/or CPDT in lipedema and cellulite. Expression of factors stimulating angiogenesis and lymphangiogenesis such as VEGF was not induced by SWT and/or CPDT and, therefore, not involved in beneficial effects by SWT and/or CPDT.

Aim: In pathophysiology of lipoedema, almost exclusively seen in women, lymphatic insufficiency might play a significant role. However, little is known about the pathophysiology of these abnormal localized depositions of body fat. We studied the involvement of the lymphatic system in lipoedema of the type Allen-Hines as well as of Typus Rusticanus Moncorps. Patients, methods: The standard (epifascial pathway) and a modified method (subcutaneous pathway) of lymphoscintigraphy was carried out with 28 patients suffering from lipoedema. Uptake percentages normalized to the injected dose were used as functional quantitative parameters. Visual assessment of both studies were done and scored. Patients with oedema of the legs because of venous insufficiency (Widmer stage II) served as a control group. Results: All patients of the control group and all patients with lipoedema of Typus Rusticanus Moncorps showed a normal standard lymphoscintigraphic study by visual scoring as well as by quantitative outcome. Lymph transport from the subcutaneous fat tissue was significant higher (p <0.012) in the group of patients with lipoedema diagnosed as type Allen-Hines than in Typus Rusticanus Moncorps. Conclusion: Epifascial lymph drainage in patients with lipoedema is not significantly disturbed. However, subcutaneous lymphatic drainage significantly differed in patients with lipoedema of type Rusticanus Moncorps in comparison with type AllenHines hinting at a differing lymphatic pathophysiology.

PURPOSE: To evaluate the accuracy of computed tomography (CT) scan imaging in distinguishing lymphedema from deep venous thrombosis (DVT) and lipodystrophy (lipedema) in patients with swollen legs. MATERIAL AND METHODS: CT scans of the lower limbs were performed in 55 patients with 76 swollen legs (44 lymphedemas, 12 DVT and 20 lipedemas). Thirty-four normal contralateral legs were also similarly evaluated. Primary lymphedema was verified by lymphography or lymphoscintigraphy, whereas secondary lymphedema was documented by a typical clinical history. DVT was established by ultrasound Doppler imaging. The diagnosis of lipedema was made with bilateral swollen legs where lymphoscintigraphy and Doppler examination were both unremarkable. Qualitative CT analysis was based on skin thickening, subcutaneous edema accumulation with a honeycombed pattern, and muscle compartment enlargement. RESULTS: Sensitivity and specificity of CT scan for the diagnosis of lymphedema was 93 and 100%, respectively; for lipedema it was 95 and 100%, respectively; andfor DVT it was 91 and 99%, respectively. Skin thickening was found in 42 lymphedemas (95%), in 9 DVT (75%), and in 2 lipedemas (16%). Subcutaneous edema accumulation was demonstrated in 42 legs (95%) with lymphedema and in 5 (42%) with DVT but in none with lipedema. A honeycombed pattern was present only in lymphedema (18 legs or 41%); muscle enlargement was present in all patients with DVT, in no patient with lipedema, and in 4 (9%) with lymphedema. CONCLUSION: Edema accumulation is readily demonstrated with plain CT scan and is not present in lipedema. Specific CT features of the subcutaneous fat and muscle compartments allow accurate differentiation between lymphedema and DVT.

"Lipedema," a special form of obesity syndrome, represents swelling of the legs due to an increase of subcutaneous adipose tissue. In 12 patients with lipedema of the legs and in 12 healthy subjects (controls), fluorescence microlymphography was performed to visualize the lymphatic capillary network at the dorsum of the foot, at the medial ankle, and at the thigh. Microaneurysm of a lymphatic capillary was defined as a segment exceeding at least twice the minimal individual diameter of the lymphatic vessel. In patients with lipedema, the propagation of the fluorescent dye into the superficial lymphatic network of the skin was not different from the control group (p > 0.05). In all 8 patients with lipedema of the thigh, microaneurysms were found at this site (7.9 +/- 4.7 aneurysms per depicted network) and in 10 of the 11 patients with excessive fat involvement of the lower leg, multiple microlymphatic aneurysms were found at the ankle region. Two obese patients showed lymphatic microaneurysms in the unaffected thigh and in only 4 patients were microaneurysms found at the foot. None of the healthy controls exhibited microlymphatic aneurysms at the foot and ankle, but in one control subject a single microaneurysm was detected in the thigh. Multiple microlymphatic aneurysms of lymphatic capillaries are a consistent finding in the affected skin regions of patients with lipedema. Its significance remains to be elucidated although its occurrence appears to be unique to these patients.

The role of operative management of "symptomatic" varicose veins in patients with lower extremity lymphedema or lipedema is controversial. We reviewed the clinical outcome of 261 patients between 1989-1997 at the Földiclinic with lower extremity lymphedema (68 patients), lipo-lymphedema or lympho-lipedema (103 patients) or lipedema (90 patients) who had undergone operation for varicose veins. In each group, the results were dismal as leg swelling worsened or was unchanged in greater than 90% whereas symptoms such as heaviness, fatigue, cramps (termed varicogenic symptomatology) were improved in less than 10%. These findings support that operations for varicose veins in the legs of patients with lymphedema, lipedema, or combinations of these disorders should be undertaken only if there is an absolute indication present (ascending phlebitis and/or bleeding). Otherwise, complete decongestive physiotherapy is still the best treatment approach for these groups of patients.

In order to develop further the criterias of the ultrasonographic diagnosis of the lip- and lymphedema, also in the demarcation of the phlebedema, we examined 100 patients in our practice. In addition to the specific “sonomorphology”of the lip- and lymphedema we found a different reaction of the subcutaneous tissue of the lower leg in painful and not painful lipedemas examined with compression-sonography. A more precise demarcation of the cutis from the subcutis was made possible with a new 13 MHz linear probe. The spontaneous painful lipedema shows a thickened subcutis with increased echogenity and is only compressible at 10 to 20 percent, while the not painful lipedema is compressible at about 50 percent. In patients with lymphedema the typical echoless gaps showed no colour coding and were also not compressible. Especially because of the low time needed, the non-invasive method and the lack of radiation the ultrasonographic description, measurement and compression of the subcutaneous tissue of the lower leg is useful for diagnosis, the objective control of therapeutic strategies and the estimation of the clinical symptoms – especially in cases of lipedema – and also for the etiology – especially in cases of lymphedema. The sonography is superior to the clinical examination and should be the second step in diagnosis of all nonsystemic forms of edemas of the legs.