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The term lipedema is misleading, although it is true that there is an alteration of the fatty tissue, there is little evidence regarding edema. It is considered a disease since the last ICD‑11 (2019), included in the section of pathologies of skin, fat and subcutaneous cellular tissue. However, there are still doubts about whether it should be considered a disease or whether it is an aesthetic disorder. The diagnosis of lipedema can present challenges, since it is often confused with other nosological entities; especially with lymphedema. The aim of this task is to determine the basis for a correct differential diagnosis that helps to recognize lipedema as an entity with its own characteristics in order to facilitate its early identification. Clinical manifestations, plus the anamnesis and detailed examination of each patient, may be sufficient to reach a correct diagnosis. In case of doubt, there are tests capable of differentiating between lipedema and lymphedema. Differential diagnosis between lipedema and lymphedema should be made thoroughly and early in order to offer early advice and specific treatment to patients.

Lipedema is a chronic and progressive disease characterized by a symmetrical and bilateral swelling of the lower extremities. In general, the feet are not involved. Lipedema is believed to affect nearly 1 in 9 adult women worldwide. Despite this relatively common disease, lipedema is often confused with primary lymphedema or obesity. In clinically advanced lipedema stages, fat continues to build up and may block the lymphatic vessels causing a secondary lymphedema (Lipo-Lymphedema). We consecutively evaluated 54 women with a clinical diagnosis of lower limbs lipedema. Two doses of 99mTc-nanocolloid were injected intradermally at the first intermetatarsal space and in the lateral malleolar area. Two static planar scans were taken at rest immediately following the intradermal injection. Subsequently, all patients were asked to perform an isotonic muscular exercise (stepping) for 2 min. Then, post exercise scans were performed to monitor the tracer pathway. Subsequently, the patient was asked to take a 30-40 min walk (prolonged exercise) and delayed scans were acquired. In early clinical stages, the lymphatic flow is usually preserved and the rest/stress intradermal lymphoscintigraphy may visualize a normal lymphatic drainage with a frequent pattern (tortuous course) of the leg lymphatic pathway. In clinically advanced stages, lymph stagnation areas were observed. Unlike obesity, lipedema fat storage is resistant to dietary regimen, bariatric surgery, and physical activity. Surgical treatment (tumescent liposuction and reductive surgery) is the most effective treatment to remove adipose tissue. Complex decongestive therapies are helpful in reducing the lymph stagnation, especially in patients with advanced lipolymphedema.

Lipedema (LI) is a common yet misdiagnosed condition, often misconstrued with obesity. LI affects women almost exclusively, and its painful and life-changing symptoms have long been thought to be resistant to the lifestyle interventions such as diet and exercise. In this paper, we discuss possible mechanisms by which patients adopting a ketogenic diet (KD) can alleviate many of the unwanted clinical features of LI. This paper is also an effort to provide evidence for the hypothesis of the potency of this dietary intervention for addressing the symptoms of LI. Specifically, we examine the scientific evidence of effectiveness of adopting a KD by patients to alleviate clinical features associated with LI, including excessive and disproportionate lower body adipose tissue (AT) deposition, pain, and reduction in quality of life (QoL). We also explore several clinical features of LI currently under debate, including the potential existence and nature of edema, metabolic and hormonal dysfunction, inflammation, and fibrosis. The effectiveness of a KD on addressing clinical features of LI has been demonstrated in human studies, and shows promise as an intervention for LI. We hope this paper leads to an improved understanding of optimal nutritional management for patients with LI and stimulates future research in this area of study.

Multiple associated comorbidities have been described for lipedema patients. Disease diagnosis still remains challenging in many cases and is frequently delayed. The purpose of this study was to determine the most common comorbidities in lipedema patients and the impact of surgical treatment onto disease progression. A retrospective assessment of disease-related epidemiologic data was performed for patients who underwent liposuction between July 2009 and July 2019 in a specialized clinic for lipedema surgery. All patients received a standardized questionnaire regarding the clinical history and changes of lipedema-associated symptoms and comorbidities after surgery. 106 patients who underwent a total of 298 liposuction procedures were included in this study after returning the questionnaire fully filled-in. Multiple comorbidities were observed in the assessed collective. The prevalence for obesity, hypothyroidism, migraine, and depression were markedly increased in relation to comparable nonlipedema populations. Despite a median body mass index (BMI) of 31.6 kg/m2 (IQR 26.4-38.8), unexpected low prevalence of diabetes (5%) and dyslipidemia (7%) was found. Diagnosis and initiation of guideline-appropriate treatment were delayed by years in many patients. After surgical treatment (medium follow-up 20 months, IQR 11-42), a significant reduction of lipedema-associated symptoms was demonstrated. Lipedema occurs with a diversity of associated comorbidities. Therefore, on the basis of available data, the authors suggest the necessity of a multimodal therapy concept for a comprehensive and holistic treatment. Despite a commonly increased BMI, lipedema patients appear to have an advantageous metabolic risk profile.

<b><i>Introduction:</i></b> Lipoedema is characterized as subcutaneous lipohypertrophy in association with soft-tissue pain affecting female patients. Recently, the disease has undergone a paradigm shift departing from historic reiterations of defining lipoedema in terms of classic edema paired with the notion of weight loss-resistant leg volume towards an evidence-based, patient-centered approach. Although lipoedema is strongly associated with obesity, the effect of bariatric surgery on thigh volume and weight loss has not been explored. <b><i>Material and Methods:</i></b> In a retrospective cohort study, thigh volume and weight loss of 31 patients with lipoedema were analyzed before and 10–18 and ≥19 months after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Fourteen patients, with distal leg lymphoedema (i.e., with healthy thighs), who had undergone bariatric surgery served as controls. Statistical analysis was performed using a linear mixed-effects model adjusted for patient age and initial BMI. <b><i>Results:</i></b> Adjusted initial thigh volume in patients with lipoedema was 23,785.4 mL (95% confidence interval [CI] 22,316.6–25,254.1). Thigh volumes decreased significantly in lipoedema and control patients (baseline vs. 1st follow-up, <i>p</i> &#x3c; 0.0001 and <i>p</i> = 0.0001; baseline vs. 2nd follow-up, <i>p</i> &#x3c; 0.0001 and <i>p</i> = 0.0013). Adjusted thigh volume reduction amounted to 33.4 and 37.0% in the lipoedema and control groups at the 1st follow-up, and 30.4 and 34.7% at the 2nd follow-up, respectively (lipoedema vs. control <i>p</i> &#x3e; 0.999 for both). SG and RYGB led to an equal reduction in leg volume (operation type × time, <i>p</i> = 0.83). Volume reduction was equally effective in obese and superobese patients (weight category × time, <i>p</i> = 0.43). <b><i>Conclusion:</i></b> SG and RYGB lead to a significant thigh volume reduction in patients with lipoedema.

Background: Fluid in lymphedema tissue appears histologically as spaces around vessels and between dermal skin fibers. Lipedema is a painful disease of excess loose connective tissue (fat) in limbs, almost exclusively of women, that worsens by stage, increasing lymphedema risk. Many women with lipedema have hypermobile joints suggesting a connective tissue disorder that may affect vessel structure and compliance of tissue resulting in excess fluid entering the interstitial space. It is unclear if excess fluid is present in lipedema tissue. The purpose of this study is to determine if fluid accumulates around vessels and between skin fibers in the thigh tissue of women with lipedema. Methods: Skin biopsies from the thigh and abdomen from 30 controls and 80 women with lipedema were evaluated for dermal spaces and abnormal vessel phenotype (AVP): (1) rounded endothelial cells; (2) perivascular spaces; and (3) perivascular immune cell infiltrate. Women matched for body mass index (BMI) and age were considered controls if they did not have lipedema on clinical examination. Data were analyzed by analysis of variance (ANOVA) or unpaired t-tests using GraphPad Prism Software 7. p < 0.05 was considered significant. Results: Lipedema tissue mass increases beginning with Stage 1 up to Stage 3, with lipedema fat accumulating more on the limbs than the abdomen. AVP was higher in lipedema thigh (p = 0.003) but not abdomen skin compared with controls. AVP was higher in thigh skin of women with Stage 1 (p = 0.001) and Stage 2 (p = 0.03) but not Stage 3 lipedema versus controls. AVP also was greater in the thigh skin of women with lipedema without obesity versus lipedema with obesity (p < 0.0001). Dermal space was increased in lipedema thigh (p = 0.0003) but not abdomen versus controls. Dermal spaces were also increased in women with lipedema Stage 3 (p < 0.0001) and Stage 2 (p = 0.0007) compared with controls. Conclusion: Excess interstitial fluid in lipedema tissue may originate from dysfunctional blood vessels (microangiopathy). Increased compliance of connective tissue in higher stages of lipedema may allow fluid to disperse into the interstitial space, including between skin dermal fibers. Lipedema may be an early form of lymphedema. ClinicalTrials.gov: NCT02838277.

The article discusses the launching by MA Healthcare of the European Lipoedema Association as of October 2020 to improve the diagnosis and management of lipoedema by creating standard and evidence-based guidelines. The association was launched with the help of leading lymphology specialist Tobias Bertsch. Also cited is how lipoedema affects the adipose tissue.

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Compression hosiery is commonly used for the management of lymphoedema as well as lipoedema, but it is more commonly indicated for the lower limbs than for the upper limbs. The effects of compression hosiery on upper-limb lipoedema are poorly understood and researched. It is known that compression hosiery works in conjunction with activity or movement when standing or walking, which produces anti-inflammatory and oxygenating effects in the tissues. This effect is naturally difficult to realise in the upper limbs. Lymphoedema practitioners who treat those with lipoedema should bear in mind that compression treatment might not produce the same effects in upper-limb lipoedema as it does in lower-limb lipoedema. In these times of an overstretched health service, pragmatic resource use is essential.

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PURPOSE: Lipedema is a chronic, common but underdiagnosed disease masquerading obesity, with female predominance, characterized by disproportional abnormal adipose tissue distribution of the lower and also upper extremities. The present study was designed to determine whether lipedema is associated with three-dimensional (3D) speckle-tracking echocardiography (3DSTE)-derived left ventricular (LV) deformation abnormalities, and to assess the effects of 1-hour use of medical compression stockings (MCS). METHODS: The present study comprised 19 female patients with lipedema (mean age: 42.2 ± 12.4 years), compared to 28 age-matched healthy female controls (mean age: 42.0 ± 9.8 years). RESULTS: Lipedema patients showed larger left atrial and LV dimensions and greater LV ejection fraction than controls, without significant difference in other echocardiography variables. Lipedema patients had greater 3DSTE-derived global and mean segmental LV circumferential and area strains than controls. Following 1-hour use of wearing MCS, neither global and nor mean segmental LV strains showed significant impairment or improvement. CONCLUSIONS: Increased LV strains could be compensatory effects maintaining LV pumping function in lipedema. Short-term wearing of MCS has no global effect on LV strains.

Lipoedema is a chronic progressive disorder of adipose tissue leading to an enlargement of lower extremities. It is considered to be rare; however, the prevalence of the disease is underestimated because it is commonly misdiagnosed as obesity or lymphedema and the general awareness is poor. The etiology of the disorder is considered to be multifarious, including genetic inheritance, hormonal imbalance and microcirculation alterations. Diagnosis is mainly based on medical history and physical examination. Management of lipoedema is focused on reducing the symptoms, improving the quality of life and preventing further progression of the disease. The aim of this paper is to raise the awareness of the disease and provide appropriate clinical guidance for the assessment of lipoedema. We searched through the PubMed/MEDLINE database and took into consideration all of the results available as of 6September, 2020 and outlined the current evidence regarding lipoedema epidemiology, etiology, clinical presentation, differential diagnosis, and management. Better understanding of lipoedema is crucial for establishing an early diagnosis and a proper treatment, which in turn will reduce the psychological and physical implications associated with the disease.

Background/objectives Patients with obesity and lipedema commonly are misdiagnosed as having lymphedema. The conditions share phenotypic overlap and can influence each other. The purpose of this study was to delineate obesity-induced lymphedema, obesity without lymphedema, and lipedema in order to improve their diagnosis and treatment. Subjects/methods Our Lymphedema Center database of 700 patients was searched for patients with obesity-induced lymphedema (OIL), obesity without lymphedema (OWL), and lipedema. Patient age, sex, diagnosis, cellulitis history, body mass index (BMI), and treatment were recorded. Only subjects with lymphoscintigraphic documentation of their lymphatic function were included. Results Ninety-eight patients met inclusion criteria. Subjects with abnormal lymphatic function (n = 46) had a greater BMI (65 ± 12) and cellulitis history (n = 30, 65%) compared to individuals with normal lymphatic function [(BMI 42 ± 10); (cellulitis n = 8, 15%)] (p < 0.001). Seventeen patients had a history of lipedema and two exhibited abnormal lymphatic function (BMI 45, 54). The risk of having lower extremity lymphedema was predicted by BMI: BMI < 40 (0%), 40–49 (17%), 50–59 (63%), 60–69 (86%), 70–79 (91%), ≥80 (100%). Five patients with OIL (11%) underwent resection of massive localized lymphedema (MLL) or suction-assisted lipectomy. Three individuals (18%) with lipedema were treated with suction-assisted lipectomy. Conclusions The risk of lymphedema in patients with obesity and lipedema can be predicted by BMI; confirmation requires lymphoscintigraphy. Individuals with OIL are at risk for cellulitis and MLL. Patients with a BMI > 40 are first managed with weight loss. Excisional procedures can further reduce extremity size once BMI has been lowered.

ICD-10 Coordination and Maintenance Committee Meeting September 8-9, 2020 Lipedema and Lipolymphedema Lipedema, initially described at the Mayo clinic in 1940, is a loose, connective-tissue (fat) disease (lipomatosis) with a pathological deposition of fibrotic fatty tissue on the limbs of women sparing the trunk, hands and feet, resulting in a disproportionate body habitus. There is no specific ICD-10-CM code for lipedema. Deposition of lipedema fat increases with stage and body mass index (BMI) and likely involves sex hormones during times when weight is gained (puberty, pregnancy and menopause). Lipedema is inherited in 60% of women likely through genes affecting microvessels resulting in excess fluid bound to glycosaminoglycans in the interstitial space. Unique to lipedema is fat that is highly resistant to loss by diet, exercise, or bariatric surgery. Lipedema is often confused with secondary obesity or lymphedema. Women with lipedema and/or obesity can develop lymphedema called lipolymphedema, for which there is no ICD-10-CM code. There is no cure for lipedema, but treatments aimed at reducing the lymphedema component of lipedema such as manual decongestive therapy, wrapping, exercise, compression garments and pumps, and some medical foods and medications are helpful. Expertly performed suction assisted lipectomy is the treatment of choice for suitable lipedema patients with an inadequate response to conservative and supportive measures. Lipedema is thought to affect 11% of the female population. Lymphedema is a chronic and progressive swelling caused by a low output failure of the lymphatic system, resulting in the development of a high-protein edema in the tissues. Lymphedema is a lifelong condition for which no cure exists. Lymphedema can be either primary (hereditary) or secondary. Secondary lymphedema is the most common cause of the disease and affects approximately 1 in 1000 Americans. Complications of lymphedema include recurrent bouts of cellulitis and/or lymphangitis, bacterial and fungal infections, lymphangio-adenitis, deep venous thrombosis, poor wound healing, leg ulcers, severe functional impairment, disability, and necessary amputation. Patients with chronic lymphedema for 10 years have a 10% risk of developing lymphangiosarcoma. Praecox lymphedema is currently captured in ICD-10-CM as a secondary lymphedema; it is more accurately classified under code Q82.0: Hereditary lymphedema. With support from the American Vein & Lymphatic Society (AVLS), the requestor is submitting the following modifications to identify and track lipedema and lipolymphedema patients.

BACKGROUND: Lower extremity lymphedema is frequently encountered in the vascular clinic. Established dogma purports that cancer is the most common cause of lower extremity lymphedema in Western countries, whereas chronic venous insufficiency (CVI) is often overlooked as a potential cause. Moreover, lymphedema is typically ascribed to a single cause, yet multiple causes can coexist. METHODS: A 3-year retrospective analysis was conducted of demographic and clinical characteristics of 440 eligible patients with lower extremity lymphedema who presented for lymphatic physiotherapy to a university medical center's cancer-based physical therapy department. RESULTS: The four most common causes of lower extremity lymphedema were CVI (phlebolymphedema; 41.8%), cancer-related lymphedema (33.9%), primary lymphedema (12.5%), and lipedema with secondary lymphedema (11.8%). The collective cohort was more likely to be female (71.1%; P < .0001), to be white (78.9%; P < .0001), to demonstrate bilateral distribution (74.5%; P < .0001), and to have involvement of the left leg (bilateral, 69.1% [P < .0001]; unilateral, 58.9% [P = .0588]). Morbid obesity was pervasive (mean weight and body mass index, 115.8 kg and 40.2 kg/m(2), respectively) and significantly correlated with a higher International Society of Lymphology lymphedema stage (stage III mean weight and body mass index, 169.2 kg and 57.3 kg/m(2), respectively, vs stage II, 107.8 kg and 37.5 kg/m(2), respectively; P < .0001). Approximately one in three (35.7%) of the population sustained one or more episodes of cellulitis, but patients with stage III lymphedema had roughly twice the rate of soft tissue infection as patients with stage II, 61.7% vs 31.8%, respectively (P < .001). Multifactorial lymphedema was present in 25%. Approximately half of the patients with lipedema with secondary lymphedema (48.1%) or primary lymphedema (45.5%) had a superimposed cause of swelling that was usually CVI. Total knee arthroplasty was the most common cause of noncancer surgery-mediated worsening of pre-existing lymphedema. CONCLUSIONS: In a large cohort of patients treated in a cancer-affiliated physical therapy department, CVI (phlebolymphedema), not cancer, was the predominant cause of lower extremity lymphedema. One in four patients had more than one cause of lymphedema. Notable clinical characteristics included a proclivity for female patients, bilateral distribution, left limb, cellulitis, and nearly universal morbid obesity.

BACKGROUND: Lipedema is a condition of painful increase in subcutaneous fat affecting almost exclusively women. Several studies have examined the effectiveness of liposuction in the treatment of lipedema, but none has focused on water-jet-assisted liposuction technique. METHODS: A standardized treatment protocol for liposuction in lipedema, which was established over the course of 15 years, is presented. Patients received questionnaires preoperatively and after operative treatment assessing characteristics and symptom severity on visual analog scales in a prospective manner. RESULTS: Pre- and postoperative questionnaires were available for 63 patients. Median age was 35 years and mean (body mass index) BMI 28.4 ± 0.6, all patients had stages I or II lipedema diagnosed by two separate specialists. After a mean follow-up of 22 months after operative treatment, all assessed symptom had decreased significantly in severity. All patients wore compression garments and/or received manual lymphatic drainage preoperatively; this could be reduced to only 44% of patients needing any conservative treatment postoperatively. CONCLUSION: Liposuction in water-jet-assisted technique using the presented treatment protocol is an efficient method of operative treatment of early-stage lipedema patients leading to a marked decrease in symptom severity and need for conservative treatment.

Lipedema is an often underdiagnosed chronic disorder that affects subcutaneous adipose tissue almost exclusively in women, which leads to disproportionate fat accumulation in the lower and upper body extremities. Common comorbidities include anxiety, depression, and pain. The correlation between mood disorder and subcutaneous fat deposition suggests the involvement of steroids metabolism and neurohormones signaling, however no clear association has been established so far. In this study, we report on a family with three patients affected by sex-limited autosomal dominant nonsyndromic lipedema. They had been screened by whole exome sequencing (WES) which led to the discovery of a missense variant p.(Leu213Gln) in AKR1C1, the gene encoding for an aldo-keto reductase catalyzing the reduction of progesterone to its inactive form, 20-α-hydroxyprogesterone. Comparative molecular dynamics simulations of the wild-type vs. variant enzyme, corroborated by a thorough structural and functional bioinformatic analysis, suggest a partial loss-of-function of the variant. This would result in a slower and less efficient reduction of progesterone to hydroxyprogesterone and an increased subcutaneous fat deposition in variant carriers. Overall, our results suggest that AKR1C1 is the first candidate gene associated with nonsyndromic lipedema.

The COVID-19 pandemic poses a challenge to the management of non-COVID pathologies such as lymphatic diseases and lipoedema. The use of telemedicine can prevent the spread of the disease. A system is needed to help determine the clinical priority and selection of face-to-face or telemedicine options for each patient and how to carry them out during the pandemic. The Spanish Lymphology Group has drafted a consensus document with recommendations based on the literature and clinical experience, as clinical practice guidelines for the management of lymphatic abnormalities and lipoedema during the COVID-19 pandemic. These recommendations must be adapted to the characteristics of each patient, the local conditions of the centres, and the decisions of health care professionals. The document contains minimum criteria, subject to modifications according to the evolution of the pandemic, scientific knowledge and instructions from health authorities.

PURPOSE: The aim of this narrative review of the literature was to evaluate and summarize the current literature regarding the effect of lipedema on health-related quality of life (HRQOL) and psychological status. METHODS: The authors collected articles through a search into Medline, Embase, Scopus, Web of Science, Physiotherapy Evidence Database (PEDro), and the Cochrane Review. Search terms used included "Lipoedema," "Lipedema," "psychological status," "Quality of life," "Health related quality of life," and "HRQOL." RESULTS: A total of four observational studies were evaluated. The included studies were moderate-quality according to the Newcastle-Ottawa Scale. Three of the included studies demonstrated deterioration of HRQOL and psychological status in patients with lipedema. These studies also identify that pain and tenderness are a more common and dominant characteristic. CONCLUSION: Future studies should establish a specific approach to treat and manage lipedema symptoms. Based on this narrative review of the literature findings, we recommended for the health care provider to pay more attention to HRQOL and psychological status. Moreover, validated and adapted measures of HRQOL and psychological status for patients with lipedema are required. LEVEL OF EVIDENCE: Level V, narrative review.