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Diabetes mellitus (DM) affects 537 million people as of 2021, and is projected to rise to 783 million by 2045. This positions DM as the ninth leading cause of death globally. Among DM patients, cardiovascular disease (CVD) is the primary cause of morbidity and mortality. Notably, the prevalence rate …

Abstract Background Lipedema is a chronic, incurable disorder characterized by painful fat accumulation in the extremities. While the application of liposuction in lipedema management has become increasingly popular, the safety and effectiveness of this approach remain contentious. Our systematic review and meta-analysis aimed to assess various liposuction modalities in lipedema management to verify their safety and efficacy. Methods In-line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a comprehensive literature review from inception until March 2023 using the following electronic databases: CENTRAL, MEDLINE, Google Scholar, and EMBASE. Results From the 562 initially identified articles, 20 met our inclusion/exclusion criteria for evaluation. Our review encompassed 14 prospective cohort studies, 3 retrospective studies, 2 case series, and 1 cross-sectional study. A meta-analysis of nine articles revealed a notable improvement in the quality of life, pain, pressure sensitivity, bruising, cosmetic impairment, heaviness, walking difficulty, and itching among lipedema patients who underwent liposuction. Although complications such as inflammation, thrombosis, seroma, hematoma, and lymphedema-related skin changes were reported, severe complications were rare. Crucially, no instances of shock, recurrence, or mortality were reported. Conclusion Liposuction is a safe and beneficial therapeutic intervention for managing lipedema symptoms and enhancing quality of life. However, the impact of liposuction on secondary lymphedema remains unreported in the literature. Further high-quality, large-scale trials are necessary to assess the safety and effectiveness of different liposuction modalities. These studies will contribute valuable insights to optimize liposuction as a therapeutic option for individuals with lipedema. Level of Evidence I, risk/prognostic study.

Lipedema, a chronic and painful disorder primarily affecting women without a definitive cure, has traditionally been managed with conservative therapy, notably complete decongestive therapy, across many countries. Recently, liposuction has been explored as a potential surgical treatment, prompting this study to evaluate its effectiveness as possibly the first-line therapy for lipedema. Through extensive literature searches in databases such as CrossRef, Web of Science, PubMed, and Google Scholar up to December 2023, and using the Newcastle-Ottawa Scale for quality assessment, the study selected seven studies for inclusion. Results showed significant post-operative improvements in spontaneous pain, edema, bruising, mobility, and quality of life among lipedema patients undergoing liposuction. However, over half of the patients still required conservative therapy after surgery. Despite these promising results, the study suggests caution due to lipedema's complexity, significant reliance on self-reported data, and limitations of the studies reviewed. Thus, while liposuction may offer symptomatic relief, it should be considered an adjunct, experimental therapy rather than a definitive cure, emphasizing the need for a comprehensive approach to care.

Introdução: O lipedema, recentemente introduzido na 11ª revisão da Classificação Internacional de Doenças. Estima-se que metade das pessoas acometidas pelo lipedema, estejam em sobrepeso ou com obesidade, sendo uma associação de comorbidades que dificulta o diagnóstico. O diagnóstico errôneo é preocupante, pois atrasa o tratamento da doença permitindo a sua progressão. Objetivo: Trata-se de uma revisão integrativa da literatura (RIL) com objetivo de analisar o que se tem construído em pesquisas anteriores relacionadas ao lipedema. Metodologia: A busca dos artigos científicos foram os disponibilizados nos Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Os artigos constassem os Descritores em Ciências da Saúde (DeCS) com as palavras: lipedema and procedimento and cirurgia and mulher, e que fossem revisados por pares, nas línguas inglesa e portuguesa. a partir da aplicação dos critérios previamente definidos O período de busca foi realizado nos meses de maio a agosto de 2023. Resultados e Discussão: Foram elegíveis 12 artigos. A análise dos artigos encontrados possibilitou a evidente necessidade de conhecimento e clareza no diagnóstico do lipedema. As mulheres são as mais afetadas pela doença. A área afetada pode incluir os quadris, as pernas bilateral e simetricamente. E uma das principais características distintivas do lipedema é a preservação dos pés, o que pode criar um degrau distinto no tornozelo. Assim, a importância do diagnóstico diferencial. O procedimento cirúrgico como tratamento apresentou melhores resultados. Entretanto, a associação de todos os tratamentos sobressaiu na qualidade de melhora dos aspectos do lipedema. Conclusão: Essa revisão apontou para o complexo  diagnóstico do lipedema.  Esse assunto persiste como um desafio e deve instigar mais pesquisadores na busca para um diagnóstico preciso, opções de tratamento e até mesmo no sentido de prevenção para satisfazer a população assistida, no caso a maioria são as mulheres.  A melhor opção indicada pelos estudos analisados foi o tratamento cirúrgico realizado pela lipoaspiração.

BACKGROUND: Lipedema, a complex and enigmatic adipose tissue disorder, remains poorly understood despite its significant impact on the patients' quality of life. Genetic investigations have uncovered potential contributors to its pathogenesis, including somatic mutations, which are nonheritable genetic alterations that can play a pivotal role in the development of this disease. AIM: This review aims to elucidate the role of somatic mutations in the etiology of lipedema by examining their implications in adipose tissue biology, inflammation, and metabolic dysfunction. RESULTS: Studies focusing on leukocyte clones, genetic alterations like TET2 and DNMT3A, and the intricate interplay between adipose tissue and other organs have shed light on the underlying mechanisms driving lipedema. From the study of the scientific literature, mutations to genes correlated to three main pathways could be involved in the somatic development of lipedema: genes related to mitochondrial activity, genes related to localized disorders of subcutaneous adipose tissue, and genes of leukocyte clones. CONCLUSIONS: The insights gained from these diverse studies converge to highlight the complex genetic underpinnings of lipedema and offer potential avenues for therapeutic interventions targeting somatic mutations to alleviate the burden of this condition on affected individuals.

PURPOSE OF REVIEW: This review aims to provide an overview of the current evidence on the efficacy, also considering the anti-inflammatory properties and safety of very low-calorie ketogenic diet (VLCKD) as a potential treatment for lipedema, particularly in the context of obesity. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal and painful fat buildup on the legs and/or arms. It is often misdiagnosed as obesity or lymphedema. However, although lipedema and obesity can coexist, unlike obesity, lipedema usually affects the legs and thighs without affecting the feet or hands, and the abnormal deposition of adipose tissue in lipedema is painful. The current lifestyle interventions are often unsuccessful in the management of lipedema. There is no consensus on the most effective nutritional approach for managing lipedema. Recent studies have suggested that VLCKD may be an effective treatment for lipedema, demonstrating that it is also superior to other nutritional approaches such as Mediterranean diet or intermittent fasting. Lipedema is a chronic and debilitating disease characterized by abnormal and painful accumulation of adipose tissue in the legs. VLCKD has been shown to be an effective treatment for lipedema, especially in the context of obesity, due to its anti-inflammatory properties. However, further research is needed to determine the long-term safety and efficacy of VLCKD as a treatment for lipedema.

Lymphangiogenesis is the mechanism by which the lymphatic system develops and expands new vessels facilitating fluid drainage and immune cell trafficking. Models to study lymphangiogenesis are necessary for a better understanding of the underlying mechanisms and to identify or test new therapeutic agents that target lymphangiogenesis. Across the lymphatic literature, multiple models have been developed to study lymphangiogenesis in vitro and in vivo. In vitro, lymphangiogenesis can be modeled with varying complexity, from monolayers to hydrogels to explants, with common metrics for characterizing proliferation, migration, and sprouting of lymphatic endothelial cells (LECs) and vessels. In comparison, in vivo models of lymphangiogenesis often use genetically modified zebrafish and mice, with in situ mouse models in the ear, cornea, hind leg, and tail. In vivo metrics, such as activation of LECs, number of new lymphatic vessels, and sprouting, mirror those most used in vitro, with the addition of lymphatic vessel hyperplasia and drainage. The impacts of lymphangiogenesis vary by context of tissue and pathology. Therapeutic targeting of lymphangiogenesis can have paradoxical effects depending on the pathology including lymphedema, cancer, organ transplant, and inflammation. In this review, we describe and compare lymphangiogenic outcomes and metrics between in vitro and in vivo studies, specifically reviewing only those publications in which both testing formats are used. We find that in vitro studies correlate well with in vivo in wound healing and development, but not in the reproductive tract or the complex tumor microenvironment. Considerations for improving in vitro models are to increase complexity with perfusable microfluidic devices, co-cultures with tissue-specific support cells, the inclusion of fluid flow, and pairing in vitro models of differing complexities. We believe that these changes would strengthen the correlation between in vitro and in vivo outcomes, giving more insight into lymphangiogenesis in healthy and pathological states.

As overweight and obesity rates have increased worldwide, the prevalence of metabolic disorders has also grown. Due to the lack of physiologically relevant adipose tissue platforms, research in adipose tissue biology has relied on animal models, leading to false conclusions on pathophysiological mechanisms and therapeutic efficacy. Despite the urgent need for an adipose tissue model, it is still extremely difficult to cultivate mature adipocytes and recapitulate multi-cellular interactions in adipose tissue in vitro. For this reason, adipose tissue modeling requires new technologies that allow better culture conditions for adipocytes and contain a complex network of microenvironments. Herein, we discuss recent technologies, including 3-dimensional (3D) adipocyte spheroids, biomaterial-based 3D culture, 3D bioprinting, and microphysiological systems, which may offer new opportunities to discover drugs targeting adipose tissue.

When studying the current literature, one might get the impression that lipedema is a “modern” disease, with increasing incidence and augmenting prevalence throughout Western countries during the last decade. However, a quick look into older textbooks shows that disproportionate accumulation of fat in female bodies has long been known without being recognized as an independent disease. Nevertheless, it was not until 1940 that Allen and Hines described a “syndrome characterized by fat legs and orthostatic edema” in a seminal publication. The mere awareness that people who have lipedema are not just overweight but suffer from a yet poorly defined pathological condition, may be considered a decisive leap forward in the understanding of lipedema. A number of comprehensive publications have since dealt with the clinical presentation of lipedema and have provided the first clues towards the potential pathological mechanisms underlying its initiation and progression. Nevertheless, despite all effort that has been undertaken to unravel lipedema pathology, many questions have remained unanswered. What can be deduced with certainty from all experimental and medical evidence available so far is that lipedema is neither a cosmetic problem nor is it a problem of lifestyle but should be accepted as a serious disease with yet undetermined genetic background, which makes women’s lives unbearable from both a physical and psychological point of view. To date, results from clinical inspections have led to the categorization of various types and stages of lipedema, describing how the extremities are affected and evaluating its progression, as demonstrated by skin alterations, adipose tissue volume increase and physical and everyday-behavioral impediments. There is accumulating evidence showing that advanced stages of lipedema are usually accompanied by excessive weight or obesity. Thus, it is not unreasonable to assume that the progression of lipedema is largely driven by weight gain and the pathological alterations associated with it. Similarly, secondary lymphedema is frequently found in lipedema patients at advanced stages. Needless to say, both conditions considerably blur the clinical presentation of lipedema, making diagnosis difficult and scientific research challenging. The present literature review will focus on lipedema research, based on evidence fromex vivo and in vitro data, which has accumulated throughout the last few decades. We will also open the discussion as to whether the currently used categorization of lipedema stages is still sufficient and up-to-date for the accurate description of this enigmatic disease, whose name, strangely enough, does not match its pathologic correlate.

Lipoedema is a painful non-pitting diffuse “fatty” swelling, usually confined to the legs, that occurs mainly in women. This scoping review aimed to provide an overview of the available research on the functioning of people with lipoedema, according to the International Classification of Functioning, Disability and Health (ICF) framework. Relevant publications and gray literature were retrieved until October 2022. The results sections of each publication were organized using a thematic framework approach. All included studies reported at least one outcome fitting within the domains of body functions and body structures, with most studies focusing on the categories of “sensation of pain”, “immunological system functions”, and “weight maintenance functions”. The ICF domains of activities and participation and environmental factors were mentioned in a small number of the included studies (17 and 13%, respectively), while the domain of personal factors was studied in half of the included studies. In conclusion, the emphasis of lipoedema research is on its description from a disorder-oriented point of view in the form of body functions and body structures, with a lack of information about the other domains of functioning.

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.

Edema of the lower extremities is always associated with a pathological condition that should be treated, especially in patients with chronic wounds. Because the underlying causes of edema can vary greatly and sometimes be complex, clinical and, if necessary, various diagnostic tests should also be performed. Often, a suspected clinical diagnosis can already be made after clinical inspection with testing of Stemmer's and Godet's signs. Sonographic examination should then be performed as the next diagnostic test. Although measurement techniques such as water plethysmography are currently considered gold standard for volume measurements, they are very complex and prone to error, so that they are rarely used in clinical routine today. In summary, it is recommended to perform a clinical examination, if possible in combination with sonography, for edema diagnosis. Especially at the beginning of the decongestion phase, regular circumferential measurements should be performed and documented. This documentation is of high relevance for evaluation of therapeutic success.

EXECUTIVE SUMMARY Nuclear medicine is an essential tool in the delivery of high-quality medical care, going beyond simple anatomical imaging to the use of physiological processes for both imaging and therapy. Nuclear medicine techniques were applied to the lymphatic system as early as the 1950s by Sherman et al. (1), using 198Au colloid (a beta emitter) as a therapeutic agent for lymph node metastasis. In the late 1960s and early 1970s, the ready availability of technetium-99m (99mTc) allowed more widespread lymphatic imaging (lymphoscintigraphy) with 99mTc colloid. In 1976, Ege (2) studied lymphatic flow in 848 patients, suggesting lymphoscintigraphy could demonstrate variable lymphatic drainage patterns, therefore allowing more accurate radiation therapy fields. In recent years, advances in radiopharmaceuticals and imaging technology have allowed more accurate localization of lymph nodes during lymphoscintigraphy and the development of the sentinel lymph node (SLN) concept. One of the first mentions of SLN was made in 1960 by Gould and Philben (3). They described a specific location of a node that drained the parotid gland. This node, located at the junction of the anterior and posterior facial veins, was described as the node most likely to contain metastasis. It was recommended that this node be investigated first before carrying out complete node dissection (3). The SLN concept was further explored by Cabanas (4) in 1977 when lymphangiography with contrast was used to identify a specific location for lymphatic drainage from the penis. Similar to what was described by Gould and Philben, Cabanas (4) felt that this 1 specific lymph node (located at the superficial epigastric vein by Cabanas for penile carcinoma) could be defined as the SLN for all patients. Individual variations demonstrated in the lymphatic channels and the location of the sentinel node since the initial investigations have confirmed that mapping of lymphatic drainage needs to be carried out for each patient undergoing SLN sampling. SLN identification can be done with optical agents, such as isosulfan or methylene blue, as well as with radiotracers and fluorescent tracers. Localization of the SLN(s) with these techniques in individual patients has allowed a more focused investigation of nodal drainage from a primary tumor site, preventing the morbidity and mortality of complete node bed dissection in patients with no clinical evidence of tumor in the regional nodal basin (5). One difficulty with reviewing the literature describing lymphoscintigraphy is the variety of tracers in use around the world and throughout the history of lymphoscintigraphy. Smaller particles tend to move through the lymphatics more quickly. Some tracers are more likely to stop at the first node they encounter, while others are more likely to move through the lymphatic system more readily, demonstrating channels, node beds, and central lymphatic structures. The tracer used depends on the clinical indication (e.g., sentinel node scintigraphy, lymphedema, or lymphatic vessel integrity), as well as availability and local regulations. In the United States, there are only 2 tracers generally available for clinical use: 99mTc sulfur colloid and 99mTc tilmanocept. In addition, injection techniques, imaging protocols, and camera technology can vary substantially, making comparisons between studies challenging. A discussion of these technical differences is beyond the scope of this document. These appropriate use criteria (AUC) have been developed to describe the appropriate use of radiopharmaceuticals for lymphoscintigraphy in SLN mapping and lymphedema. It is hoped that through these recommendations, nuclear medicine lymphatic imaging techniques will be used to benefit patients in the most cost-effective manner. Representatives from the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the Society for Vascular Medicine (SVM), the Australia and New Zealand Society of Nuclear Medicine (ANZSNM), the American College of Radiology (ACR), the Society of Surgical Oncology (SSO), the European Association of Nuclear Medicine (EANM), the American Head and Neck Society (AHNS), the American Society of Clinical Oncology (ASCO), the American Society of Breast Surgeons (ASBrS), the American College of Nuclear Medicine (ACNM), and the American College of Surgeons (ACS) assembled as an autonomous workgroup to develop these AUC. This process was performed in accordance with the Protecting Access to Medicare Act of 2014 (6). This legislation requires that all referring physicians consult AUC by using a clinical decision support mechanism before ordering any advanced diagnostic imaging services. Such services are defined as diagnostic magnetic resonance imaging (MRI), computed tomography (CT), and nuclear medicine procedures, including positron emission tomography (PET) and others, as specified by the Secretary of Health and Human Services in consultation with physician specialty organizations and other stakeholders (3). Lymphoscintigraphy usually causes trivial radiation exposures for the patient, the surgeon, and the staff handling any specimens that may contain radioactivity. Local regulations that address the handling of radiopharmaceuticals and exposure of the public should always be followed. Radiation exposures are also trivial for pregnant patients and infants exposed to someone who has been injected with lymphoscintigraphic agents labeled with 99mTc. The amount of radiopharmaceutical transferred from the interstitium into the blood and from the blood to the milk is very low. However, when performing an SLN procedure for breast cancer, it seems prudent to recommend the interruption of direct breastfeeding for 24 hours after administration of the radiopharmaceutical. There is a potential for more fetal or infant exposure if the radioisotope dissociates from the radiopharmaceutical; however, exposures will remain very small and likely of no consequence. The rapid decay of 99mTc (6-hour half-life) also allows for rapid return of radiation exposures to background levels within a short time. More detailed information can be found in the document “Advisory Committee on Medical Uses of Isotopes (ACMUI) Sub-Committee on Nursing Mother Guidelines for the Medical Administration of Radioactive Materials” (https://www.nrc.gov/docs/ML1803/ML18033B034.pdf).

Lipedema is an adipofascial disorder that almost exclusively affects women. Lipedema leads to chronic pain, swelling, and other discomforts due to the bilateral and asymmetrical expansion of subcutaneous adipose tissue. Although various distinctive morphological characteristics, such as the hyperproliferation of fat cells, fibrosis, and inflammation, have been characterized in the progression of lipedema, the mechanisms underlying these changes have not yet been fully investigated. In addition, it is challenging to reduce the excessive fat in lipedema patients using conventional weight-loss techniques, such as lifestyle (diet and exercise) changes, bariatric surgery, and pharmacological interventions. Therefore, lipedema patients also go through additional psychosocial distress in the absence of permanent treatment. Research to understand the pathology of lipedema is still in its infancy, but promising markers derived from exosome, cytokine, lipidomic, and metabolomic profiling studies suggest a condition distinct from obesity and lymphedema. Although genetics seems to be a substantial cause of lipedema, due to the small number of patients involved in such studies, the extrapolation of data at a broader scale is challenging. With the current lack of etiology-guided treatments for lipedema, the discovery of new promising biomarkers could provide potential solutions to combat this complex disease. This review aims to address the morphological phenotype of lipedema fat, as well as its unclear pathophysiology, with a primary emphasis on excessive interstitial fluid, extracellular matrix remodeling, and lymphatic and vasculature dysfunction. The potential mechanisms, genetic implications, and proposed biomarkers for lipedema are further discussed in detail. Finally, we mention the challenges related to lipedema and emphasize the prospects of technological interventions to benefit the lipedema community in the future.

The most relevant hallmarks of cellulite include a massive protrusion of superficial adipose tissue into the dermis, reduced expression of the extracellular glycoprotein fibulin-3, and an unusually high presence of MUSE cells in gluteofemoral white adipose tissue (gfWAT) that displays cellulite. Also typical for this condition is the hypertrophic nature of the underlying adipose tissue, the interaction of adipocytes with sweat glands, and dysfunctional lymph and blood circulation as well as a low-grade inflammation in the areas of gfWAT affected by cellulite. Here, we propose a new pathophysiology of cellulite, which connects this skin condition with selective accumulation of endogenous lipopolysaccharides (LPS) in gfWAT. The accumulation of LPS within a specific WAT depot has so far not been considered as a possible pathophysiological mechanism triggering localized WAT modifications, but may very well be involved in conditions such as cellulite and, secondary to that, lipedema.

Background: Edema is highly prevalent in patients with cardiovascular disease and is associated with various underlying pathologic conditions, making it challenging for physicians to diagnose and manage. Methods: We report on presentations from a virtual symposium at the Annual Meeting of the European Venous Forum (25 June 2021), which examined edema classification within clinical practice, provided guidance on making differential diagnoses and reviewed evidence for the use of the treatment combination of Ruscus extract, hesperidin methyl chalcone and vitamin C. Results: The understanding of the pathophysiologic mechanisms underlying fluid build-up in chronic venous disease (CVD) is limited. Despite amendments to the classic Starling Principle, discrepancies exist between the theories proposed and real-world evidence. Given the varied disease presentations seen in edema patients, thorough clinical examinations are recommended in order to make a differential diagnosis. The recent CEAP classification update states that edema should be considered a sign of CVD. The combination of Ruscus extract, hesperidin methyl chalcone and vitamin C improves venous tone and lymph contractility and reduces macromolecule permeability and inflammation. Conclusions: Data from randomized controlled trials support guideline recommendations for the use of Ruscus extract, hesperidin methyl chalcone and vitamin C to relieve major CVD-related symptoms and edema.

Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.

(1) Background: Due to insufficient knowledge of lipoedema, the treatment of this disease is undoubtedly challenging. However, more and more researchers attempt to incorporate the most effective lipoedema treatment methods. When assessing a new therapeutic method, choosing correct, objective tools to measure the therapeutic outcome is very important. This article aims to present possible instruments that may be used in the evaluation of therapeutic effects in patients with lipoedema. (2) Methods: The data on therapeutic outcome measurements in lipoedema were selected in February 2022, using the Medical University of Gdansk Main Library multi-search engine. (3) Results: In total, 10 papers on this topic have been identified according to inclusion criteria. The tools evaluating the therapeutic outcomes used in the selected studies were: volume and circumference measurement, body mass index, waist-to-hip ratio, ultrasonography and various scales measuring the quality of life, the level of experiencing pain, the severity of symptoms, functional lower extremity scales, and a 6 min walk test. (4) Conclusion: The tools currently used in evaluating the effectiveness of conservative treatment in women with lipoedema are: volume and circumference measurement, waist-to-hip ratio, body fat percentage, ultrasonography, VAS scale, quality of life scales (SF-36, RAND-36), symptom severity questionnaire (QuASiL), Lower Extremity Functional Scale and 6 min walk. Choosing a proper tool to measure the treatment outcome is essential to objectively rate the effectiveness of therapeutic method.

Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.

Background and aims: Lipoedema is a little-known condition that is often misdiagnosed. Lipoedema presents with nodular to swollen areas that can lead to induration, nodular, uneven skin, as well as dimpling and skin flap formation, most commonly on the lower extremities, more rarely on the upper extremities The accumulation of adipose tissue results in characteristic symmetrical swelling of the extremities, ending above the ankles or wrists (cuff-sign). Primary pain phenomena include localized pain, tenderness, painful tightness, and pain on touch and pressure during activities. To get an insight in necessary self-management of pain and symptoms, a narrative review was conducted to identify requirement of self-management for coping with phenomena of pain in lipoedema and associated comorbidities. Methods: The narrative literature review includes international medical and guideline databases, as well as social media reports from affected persons. Analysis was performed using the content analysis method. Requirements of self-management, coping behaviour as well as individual case descriptions were searched. Results: 48 publications were identified. Guidelines and publications on guidelines accounted for a large proportion. Presentation of results outlines the range of requirements to manage pain with a bio-psycho-social pattern in the synthesis. Limiting spontaneous and pressure pain and secondary pain phenomena such as joint pain and mobility limitations are described. The prevention of chronification of pain in association with lipoedema has not yet been a direct aim in the therapeutic strategy. Conclusions: A knowledge gap regarding the incidence of pain syndrome and chronification shows major deficits of self-management strategies and implies further research needs.