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Lipoedema is an overlooked and often misdiagnosed condition, which mainly affects women. This review summarises the present knowledge of the condition. It is characterised by bilateral and symmetrical accumulation of subcutaneous adipose tissue mainly in the legs. Patients with lipoedema often display tenderness to palpation or spontaneous pain in the adipose tissue. Lipoedema is diagnosed based on the medical history and clinical findings. Treatment includes conservative and surgical options with the aim of relieving symptoms and increasing mobility, but there is a paucity of randomised controlled trials.

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 a pathology of the adipose tissue, in evident female prevalence, diagnosed clinically and still of not well-defined etiopathogenesis. Indeed, an estrogen-related component is present, and an inflammatory state and a condition of edema are present in most cases; even pain seems to be a recurring feature, and insulin resistance is also often associated with lipedema. The therapeutic approach is finally becoming holistic. Therefore, with surgery, physiotherapy, and elastic compression therapy, the nutritional aspect of food supplementation is gaining much value. The objective of the present work is to consider the nutritional supplements that could be useful to manage this condition, underlining that, at the moment, the specific literature is practically non-existent. The most promising supplements seem to be omega 3 fish oil, polyphenols, and vitamin C, but the need for studies in this sector is urgent.

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.

An abstract is unavailable.

Das Lipödem ist eine sehr komplexe, unvermutet häufig anzutreffende Erkrankung des Fettsystems der Extremitäten. Es handelt sich hier um ein lymphologisches Krankheitsbild, wobei besonders das Baufett betroffen ist. Nur in wenigen Fällen ist es auch mit metabolischen Symptomen assoziiert. Das Lipödem ist eine Sonderform der Adipositas, die weder in der Medizin noch in der Bevölkerung als bewegungs- und diätresistent wahrgenommen wird. Die betroffenen Patienten sind in ihrem seelischen Gleichgewicht äußerst betroffen. Aufgrund unserer anatomischen Untersuchungen kann man durchaus von einer ernsthaften, progressiven Erkrankung des subkutanen Fettgewebes und der benachbarten, assoziierten Strukturen sprechen. Es ist nicht nur die Klinik, sondern auch die duplexsonographische Evaluierung und impedanzanalytische Exploration sind zur Diagnosefindung und zur postoperativen Verlaufskontrolle notwendig. Auch bestätigt ein besonderes Verhalten der Stammzellen den Pathomechanismus. Durch Ausdünnung der Dermis und Verlust der elastischen Fasern sind dermatologische Problemstellungen wie Trockenheit, Infektneigung, Vulnerabilität und Neigung zu Ekchymosen erklärbar. Hier dürfte v. a. die Funktion des dermalen Fettes beeinträchtigt sein. Aus unseren Beobachtungen geht hervor, dass insbesondere die frühzeitige operative Therapie mittels Liposuktion einen nachhaltigen Wert für Patienten im Frühstadium hat und den Patienten eine deutliche Verbesserung der Lebensqualität bringt.

A 2022 UK guideline recommends that the liposuction procedure for treatment of lipedema should only be used in the context of research because of inadequate efficacy and safety data. A 2021 US guideline recognizes that liposuction is currently the only available technique for removing abnormal lipedema tissue. The guideline has a series of consensus statements on patient selection, indications for liposuction, prevention of procedure-related adverse events, and pre- and post-surgical management. There were no recent studies on the clinical effectiveness of liposuction compared with no treatment or to alternative treatments for the treatment of lipedema.

The Wound, Ostomy and Continence Nurses (WOCN) Society charged a task force with updating the venous leg ulcer (VLU) algorithm to include the addition of lymphedema with the new title of "Compression for Lower Extremity Venous Disease and Lymphedema (CLEVDAL)." As part of the process, the task force was charged to develop consensus-based statements to serve as clinical guidance related to CLEVDAL. The 3-member task force assisted by a moderator completed a scoping literature review to identify recommendations supported by research to qualify as evidence-based and to identify areas where guidance is needed to provide CLEVDAL. Based on the findings of the scoping review, the WOCN Society convened a panel of experts to develop consensus statements to direct care for those with lower extremity venous disease and lymphedema. These consensus statements underwent a second round of content validation with a different panel of clinicians with expertise in venous disease and lymphedema management. This article reports on the scoping review and subsequent evidence-based statements, along with the generation and validation of consensus-based statements to assist clinical decision-making in the CLEVDAL algorithm.

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.

There are many different causes of leg and foot swelling, some are benign and transient, others can be debilitating and progressive. Correct diagnosis and early treatment is crucial as conservative measures are most effective before the condition is allowed to progress. Current waiting times in the UK National Health Service (NHS) after the Covid-19 pandemic are leading to delays in care for people with chronic leg swelling. Delayed or inadequate treatment for these patients can lead to irreversible tissue damage, an episode of cellulitis, and progression to leg ulceration. There is in addition a significant impact on quality of life associated with living with the pain, anxiety, and reduced mobility. The causes of acute and chronic leg and foot swelling are outlined. Diagnosis and treatment of the common causes of leg and foot swelling in the Western adult population are discussed. The mainstay of treatment for most of these conditions relies on physical therapy and graduated elastic compression garments or elastic Velcro wraps as many do not have a cure.

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.

In recent years, more attention is being paid to the hormonal aspect of lipoedema. There are suggestions that lipoedema patients may have particular imbalances or sensitivities with regard to oestrogens and/ or progesterone. This article examines the specifics of gluteofemoral fat storage during pregnancy: increased gluteofemoral storage with strong resistance to lipolysis. It then asks if hormonal dysregulation in lipoedema patients could result in a hormonal profile that mimics pregnancy. Such a profile may include high levels of oestrogens, progesterone, prolactin and relaxin, or any combination of the above. This pseudopregnancy hormonal profile would instruct the body to store gluteofemoral fat and strongly resist all attempts to mobilise it.

2 Abstract 2.1 Participating professional associations and organisations These guidelines for the diagnosis and treatment of varicose veins were prepared under the guidance of the Deutsche Gesellschaft für Phlebologie e. V. (DGP) in cooperation with the Deutsche Gesellschaft für Gefäßchirurgie und Gefäßmedizin—Gesellschaft für operative, endovaskuläre und präventive Gefäßmedizin e. V. (DGG), the Deutschen Gesellschaft für Angiologie, Gesellschaft für Gefäßmedizin e. V. (DGA), the Deutsche Dermatologischen Gesellschaft (DDG), the Deutsche Gesellschaft für Dermatochirurgie e. V. (DGDC), the Berufsverband der Phlebologen e. V. (BVP), and the Arbeitsgemeinschaft der niedergelassenen Gefäßchirurgen Deutschlands e. V. (ANG). This updated 2018/2019 version is based on the guidelines agreed and drafted by the same associations in 2004 and 2009, and it was adopted by the Boards of the participating professional associations on 30 April 2019. 2.2 Development stage of the guidelines These guidelines are based on a structured consensus process, drawing on published data to create consensus-based guidelines at development stage S2k. 2.3 Delegates of the professional associations See: https://www.awmf.org/uploads/tx_szleitlinien/037-018l_S2k_Varikose_Diagnostik-Therapie_2019-07.pdf. 2.4 Selected literature The recommendations are based on the same publications used in previous versions and a systematic literature review carried out on 21 July 2016 in the German Institute for Vascular Public Health Research (DIGG). The review included randomised studies, meta-analyses, and controlled studies. The literature search was carried out in the Medline and PubMed databases with the following search fields in German and/or English: sclerotherapy, endovenous thermal ablation, mechanochemical ablation, cyanoacrylate glue, surgical procedures (stripping), and diagnosis, prognosis, and postoperative care of varicose veins. A manual search was carried out for later publications up to December 2018.