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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.

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.

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.

BACKGROUND: Long-term results following liposuction in patients with lipoedema are available only for an average period of 4 years. OBJECTIVE: To find out whether the improvement of complaints persists for a further 4 years. METHODS: In a single-centre study, 85 patients with lipoedema had already been examined after 4 years. A mail questionnaire - often in combination with clinical controls - was repeated after another 4 years (8 years after liposuction). RESULTS: Compared with the results after 4 years, the improvement in spontaneous pain, sensitivity to pressure, oedema, bruising and restriction of movement persisted. The same held true for patient self-assessment of cosmetic appearance, quality of life and overall impairment. Eight years after surgery, the reduction in the amount of conservative treatment (combined decongestive therapy, compression garments) was similar to that observed 4 years earlier. CONCLUSION: These results demonstrate for the first time the long-lasting positive effects of liposuction in patients with lipoedema.

Lipedema is a chronic disorder characterized by abnormal distribution of subcutaneous adipose tissue on the proximal extremities, pain and capillary fragility. Its etiology is unknown but in analogy to central obesity, chronic low-level inflammation in adipose tissue has been suggested. There seems to be an increased propagation of pre-adipocytes into mature adipocytes contributing to the massive enlargement of subcutaneous adipose tissue. We investigated whether tyrosine kinases might be involved. Proteins from adipose tissue harvested during microcannular tumescent liposuction in lipedema and in lipomas were subjected to 10% polyacrylamide-gel, transferred to a polyvinylidenfluorid membrane and immunoblotted with indicated P-Tyr-100 antibody followed by enhanced chemiluminescence reaction. A survey of all blots did not reveal tyrosine-phosphorylated proteins with a molecular weight >100 kD in lipedema tissue and controls. These investigations suggest absence of activated growth factor receptors. Some signals indicating unspecific tyrosine-phosphorylation of smaller proteins were detected in tissue of both lipedema patients and controls. The present data suggest that there is no enduring activation of tyrosine kinase pathways of adipogenesis in lipedema as in lipoma controls.

PURPOSE: Lipoedema is a chronic, progressive adipose disorder of unknown etiology, often underdiagnosed or misdiagnosed as obesity. It manifests itself with accumulation of the fat in lower parts of the body and associated edema and, due to numerous physical and psychological consequences, affects the quality of life (QOL) of those who suffer. The aim of this study was to investigate the psychological factors that might have an impact on the QOL of women with lipoedema from the contextual behavioral viewpoint. METHODS: In an Internet-based cross-sectional study, women suffering from lipoedema (N = 120) were asked to fill in questionnaires assessing: symptom severity, QOL (WHOQOL-BREF), satisfaction with life (SWLS), psychological flexibility (Acceptance and Action Questionnaire-II), social connectedness (Social Connectedness Scale-Revised) and other psychological factors. The majority of participants were from the USA, the UK, and Australia. RESULTS: Multiple hierarchical regression analyses showed that a higher level of QOL was predicted by higher levels of psychological flexibility and social connectedness, while controlling for symptom severity. Higher level of SWL was predicted only by higher level of social connectedness. CONCLUSIONS: Acceptance and Commitment Therapy with psychological flexibility as the target of change and Functional Analytic Psychotherapy with social connectedness as the target of change might be useful in treating women with lipoedema; however, further research in this area is needed. The authors conclude that psychological and biomedical interventions for women with lipoedema and their QOL merit more attention from researchers and the medical community than is currently received.

INTRODUCTION: Liposuction for lymphoedematous limbs is an effective treatment for chronic lymphoedema, with excellent long-term results in well-selected patients. In 2008 NICE produced guidelines 'Liposuction for Chronic lymphoedema', acknowledging this treatment modality. However, there remain very few centers that provide this service in the United Kingdom. We aim to share our experience of our referral system at Ninewells Hospital, Dundee, Scotland. METHODS: A 10 year prospective database from 2005 to 2014 was analysed. Referral sources, patient demographics, diagnosis and treatment offered were examined. RESULTS: There were 221 referrals in total, 190 (86%) female and 31 (14%) male. The mean age was 51 (range 7-86 years). 127 (58%) were referred via their general practitioners, 72 (33%) from a hospital consultant and 22 (10%) from a lymphoedema nurse specialist. 153 (69%) referrals were from Scotland, 61 (28%) from England and 7 (3%) from Northern Ireland. The majority of patients 165 (75%) were referred with lower limb swelling. Following assessment in clinic, 146 (66%) were found to have lymphoedema whilst the rest were deemed to have other non-lymphoedematous diagnoses which include lipoedema (47, 21%), dependent oedema (8, 4%) and obesity (5, 2%). 131 (59%) were offered liposuction- 74 (34%) have received liposuction, 18 (8%) are awaiting their procedure, 3 (1%) have declined surgery, 27 (12%) are awaiting funding approval and 9 (4%) have been declined funding by their primary care trust/clinical commissioning group (PCT/CCG). 4 (2%) are awaiting investigations to further evaluate the cause of their swelling, whilst the remaining 86 (39%) were felt unsuitable for surgery and were treated conservatively. CONCLUSION: Chronic lymphoedema is a challenging condition to treat, with few specialist centers offering surgical treatment. We hereby share our referral process, diagnosis and management.

Background: Lipedema is a poorly known disorder of painful subcutaneous adipose tissue (SAT) likely affecting millions of women worldwide. Stage 1 lipedema has smooth skin with increased underlying fat, Stage 2 has indentations and nodules, and Stage 3 has large extrusions of skin and SAT. Women with lipedema have more SAT below the waist. As this gynoid fat is known to be cardioprotective, we aimed to determine if health declined with increasing stage and extent of lipedema SAT. Methods and Findings: Chart review from June 2012 to February 2013 at a tertiary academic center. Fifty women and one man were included in consecutive order. Fat was assessed in 29 areas for lipomas, size of the depot, and presence of lipedema fat. Pain was assessed by a numerical pain scale. Average age of patients was 50 ± 13 y; average body mass index was 38 ± 12 kg/m2. Median age of development of lipedema was 20 y. Pain occurred daily in 89.7%. None of the patients with Stage 1 lipedema had diabetes, hypertension or dyslipidemia. The amount of lipedema fat differed significantly between Stages of lipedema (p=0.003), with Stage 3 having significantly more. There was no difference in fat depot size or number of lipomas amongst Stages. Only one of 51 patients had type 2 diabetes. There was an increase in shortness of breath, palpitations, urination, and numbness in Stage 3. Conclusions: Lipedema fat can develop in any SAT location and increases in association with increasing signs and symptoms of systemic illness.

Background: Lipedema is a painful, genetically induced, abnormal deposition of subcutaneous fat in the extremities of women. The pathogenesis is unknown. Also unknown is the number of women affected in Germany. This study presents the epidemiology of the disease. There are currently two treatment options available: Complex physical decongestive therapy and liposuction. Liposuction is the only method that removes fat permanently. An additional study proves its effectiveness and highlights its vital role as part of a comprehensive treatment concept.

AIM: Application of microcurrents of bioresonance may allow protein aggregates lysis and a related enhancement of lymphatic drainage. Combining bioresonance with transcutaneous passage of active principles, by means of skin electroporation, microcirculation and clearance of connective tissues may be theoretically activated. A pilot study on an electro-medical device which includes these two technologies (Transponder(®)), has been performed on patients affected by lymphedema (LYM) and/or lipedema (LIP) of the lower limbs. METHODS: Eight patients affected by primary or secondary unilateral LYM or LIP were submitted to six consecutive daily sessions with the medical device; the first two sessions were performed by a trained physiotherapist, whilst the following four sessions were self-administered by the patients themselves at home (who were educated about the technique). Magnesium silicate was delivered transcutaneously by means of the device at each session. Pre-post-treatment assessment included: 1) limb volumetry by means of tape measurement; 2) segmental multifrequency bioimpedance spectroscopy for fluid changes, with L-DEX measurement; 3) visual analogue scale (VAS) (0-10 score) questionnaire for related symptoms. RESULTS: All the patients completed the scheduled treatment. After the treatment the mean volume of the whole limb decreased from 9462.85 (±3407.02) to 9297.37 cc (±3393.20), which accounts for a 165.48 cc (2%) reduction after six days of treatment. The pre/post-treatment VAS mean score changes were: heaviness from 4.57±3.46 to 2.43±2.57 (-47%), dysesthesias from 1.71±2.63 to 0.71±1.50 (-58%), pain from 1.57±2.57 to 0.57±0.79 (-64%). Diuresis VAS measurement passed from 7.43±1.81 to 8.57±0.98 (15% increase). The average L-DEX percentage reduction was 21%. No side effects were reported and a good patients' compliance was recorded. CONCLUSIONS: The preliminary data of this pilot study show that the combination of microcurrents of bioresonance with transdermal delivery of active principles indicate that it could result in edema decrease and symptom improvement in patients affected by LYM and/or LIP of the lower limbs. Self-administered modality of the electrical device is possible and effective; no side effects have been reported.

BACKGROUND: Distinguishing lymphoedema from lipoedema in women with swollen legs can be difficult. Local tissue water content can be quantified using tissue dielectric constant (TDC) measurements. OBJECTIVES: To examine whether TDC measurements can differentiate untreated lower extremity lymphoedema from lipoedema, and to test interobserver agreement. METHODS: Thirty-nine women participated in the study; 10 patients with lipoedema (LipP), nine patients with untreated lymphoedema (U-LP), 10 patients with lymphoedema treated with compression bandaging for ≥ 4 weeks (T-LP) and 10 healthy controls. All subjects were measured at three predefined sites (foot, ankle and lower leg). All groups except U-LP were measured by three blinded investigators. Using a handheld device, a 300-MHz electromagnetic wave is transmitted into the skin via a 2.5-mm depth probe. TDC calculated from the reflected wave is directly proportional to tissue water content ranging from 1 (vacuum) to 78.5 (pure water). RESULTS: Mean ± SD TDC values for U-LP were 48.8 ± 5.2. TDC values of T-LP, LipP and controls were 34.0 ± 6.6, 29.5 ± 6.2 and 32.3 ± 5.7, respectively. U-LP had significantly higher TDC values in all measurement sites compared with all other groups (P < 0.001). A cut-off value of 40 for ankle and lower-leg measurements correctly differentiated all U-LP from LipP and controls. Intraclass correlation coefficients were 0.94 for the ankle and the lower leg and 0.63 for the foot. CONCLUSIONS: TDC values of U-LP were significantly higher than those of T-LP, LipP and controls and may aid in differentiating lymphoedema from lipoedema. Interobserver agreement was high in ankle and lower-leg measurements but low in foot measurements.

OBJECTIVES: Patient-relevant treatment benefit is traditionally measured with health-related quality of life (HRQoL) instruments. The Patient Benefit Index (PBI) methodology allows for a more direct measurement, with the patients rating both importance and achievement of treatment goals. Here, we developed and validated a PBI version specific for the assessment of benefit in lymphedema and lipedema treatment (PBI-L). METHODS: The development included five steps: (1) open item collection; (2) consensus of items in a multidisciplinary expert panel; (3) application of the German PBI-L in a cross-sectional study (n = 301); (4) translation into English; (5) application of the English PBI-L in a randomized clinical trial (n = 82). Subscales were developed using factor analysis. Construct validity was analyzed by correlating PBI-L and convergent criteria such as HRQoL and quality of care. To test for responsiveness, the association to change in HRQoL measures was computed. RESULTS: Floor and ceiling effects were low. There were few missing values. Two well-interpretable subscales were found with Cronbach's alpha >0.8 each. Global and subscale scores correlated with convergent criteria and with change in disease-specific HRQoL, but not with change in generic HRQoL. CONCLUSIONS: The PBI-L is an internally consistent, valid, and responsive instrument for the assessment of patient-relevant benefit of edema treatment.

In 2014 250 women with Lipoedema took part in our survey about their experiences with Lipoedema. The results give a clear picture of what living with Lipoedema is like and reveal that along with the pain and discomfort caused by Lipoedema, many simple tasks that other people regard as straightforward become extremely challenging for people with Lipoedema. Lipoedema UK’s Big Survey 2014 led to the development of the Royal College of GPs’ e-learning course, a half hour course, which enables GPs to recognise Lipoedema and diagnose patients Our survey was created by Lipoedema UK, the Lymphoedema Department at St George’s Hospital, London, and the support of the Lymphoedema Support Network.