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(1) Background: Although lipedema has gained more interest among researchers, specific treatment methods are still unknown. This study aims to identify the effects of compression therapy combined with exercises compared to exercising only. Moreover, the aim is to assess the methodology and outcome measurements before conducting a larger study. (2) Methods: Six women with lipedema were enrolled in the study; three were undergoing exercise program and compression therapy using compression leggings, and the remaining three were undergoing exercises only. During the first 4 weeks, intervention was under the supervision of a physiotherapist, and in the remaining weeks, participants were exercising independently. Measurements of circumference, weight, thickness of the skin and adipose tissue, symptom severity, and quality of life were taken at baseline, after 4 weeks and after 6 weeks; (3) Results: There was a significant decrease in the subjectively reported tendency for bruising and pain at palpation among patients that received compression therapy. Additionally, there was a tendency to reduce or maintain the circumference of the legs in patients using compression, while it tended to increase in patients without compression. (4) Conclusions: Preliminary results indicate that compression therapy, combined with exercises, could improve the quality of life and decrease the severity of lipedema symptoms. Further studies on a large clinical group are advisable.

Lipedema is a chronic adipose tissue disorder affecting approximately 11% of women worldwide. The illness is often misdiagnosed as obesity, and because of this, women often struggle in meetings with healthcare providers. Few studies have assessed these encounters of younger women with lipedema. The aims of this qualitative study were to explore women’s experiences in meetings with healthcare providers and the importance of social support and belonging, with a focus on younger women. Fifteen women with lipedema between the ages of 21 and 47 years (mean age 36.2 years) were interviewed. The results indicated that women felt stigmatized by healthcare providers and that younger women in their 20s and early 30s struggled more often than women of higher age when receiving their diagnosis. The feeling of shame and stigma were also dependent on the woman’s resources in handling the illness. The younger women reported that their self-confidence and romantic relationships were challenging. Social support and the feeling of belonging through romantic relationships or support groups were important resources for managing the illness. Highlighting the experiences of women may aid in increasing recognition and knowledge of lipedema. This in turn may reduce the stigma and lead to equitable healthcare services.

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.

Lipedema is a pathologic accumulation of adipose tissue in the subcutaneous layer of the extremities. This connective tissue disorder, which predominately affects females, is often misdiagnosed despite an incidence of ∼11%. Misdiagnosis often leads to delays in appropriate treatment, further increasing the morbidity of the condition. The authors report their facilities' experience in treating a patient with lipedema, requiring multiple surgical interventions involving liposuction and skin debulking to achieve desired aesthetic outcomes. The patient presented to the plastic surgery clinic with severe lipedema of the bilateral lower extremities. She previously underwent a panniculectomy and bilateral lower extremity liposuction without achieving the desired aesthetic results. Prior conservative management and liposuction alone were both unsuccessful treatment options and she required debulking procedures, along with further liposuction, as definitive management. The patient underwent 2 procedures at the clinic, both consisting of liposuction and panniculectomy of the lower extremities and buttocks. The procedures were conducted 1 year apart but were able to achieve the patient's desired aesthetics goals. Management of lipedema can be challenging, but not impossible. This case report shows that local excision is a viable option for treatment if minimally invasive options yield limited results.

Introduction: The pathologic features of fatty tissue in lipedema are often challenging to diagnose, thus allowing for variable bias and leading to underdiagnosis. Lipedema is a disease that is currently little known worldwide, but it represents a public health problem and demands immediate, well-directed healthcare. Insufficient scientific information limits medical action, which limits making diagnoses and addressing an adequate multidisciplinary treatment. This study aims to evaluate the current state of lipedema in Spain to contextualize the disease’s pathophysiological characteristics and thus achieve a consensus that unifies and defines its diagnostic criteria and medical management. Likewise, this study aims to determine the effectiveness of the various treatments applied to the study patients and to evaluate the consequences of the pandemic related to this disease. Material and methods: The present work is a descriptive, cross-sectional study that analyzed online questionnaires. It was applied to 1069 patients and collected over 9 months between 2021 and 2022. The questionnaires were distributed to the leading national and regional associations of patients affected by lipedema. The study included all patients in a group who had a diagnosis of lipedema and in a group of undiagnosed patients with six or more symptoms. The variables analyzed were age, weight, height, body mass index (BMI), type of lipedema (according to Schingale’s classification), symptoms (according to Wolf’s classification, modified by Herbst), and treatments performed (physiotherapy, compression garments, sports, diet, radiofrequency, mesotherapy, and surgery), associated with the score given by the patients regarding the degree of improvement in their disease with each of these treatments. Results: There were 967 women and 2 men between 18 and 75 years old (mean of 38.5 years); a body weight between 33 and 150 kg (mean 75.8 kg); a height between 144 and 180 cm (mean 164 cm); and an average body mass index (BMI) of 28.1. The most common kind of lipedema in our study population was type III (affecting the hips, thighs, and calves). The treatment that individually improved patients’ quality of life the most was surgery, only surpassed by the multidisciplinary approach to the disease, including conservative measures. Conclusions: With this study, we can conclude that, in Spain, there is a real problem associated with the diagnosis of lipedema, specifying the need to seek this diagnosis actively and propose multidisciplinary management, since it offers the best overall results, of course not without forgetting that surgery is one of the most critical pillars in the approach to this disease. Consistent with the results obtained in this study, criteria were proposed and applied to represent a statistical value at the time of ruling on the clinical diagnosis of lipedema, considering that a patient who presents six or more of these diagnostic criteria, with a very high probability, will have lipedema.

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.

Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macrophage composition and involved signaling pathways, anatomically matched lipedema and control tissue samples were collected intra-operatively from gender- and BMI-matched patients, and the Stromal Vascular Fraction (SVF) was used for Cytometry by Time-of-Flight (CyTOF) and RNA sequencing. The phenotypic characterization of the immune component of lipedema versus control SVF using CyTOF revealed significantly increased numbers of CD163 macrophages. To gain further insight into this macrophage composition and molecular pathways, RNA sequencing of isolated CD11b+ cells was performed. The analysis suggested a significant modification of distinct gene ontology clusters in lipedema, including cytokine-mediated signaling activity, interleukin-1 receptor activity, extracellular matrix organization, and regulation of androgen receptor signaling. As distinct macrophage populations are known to affect adipose tissue differentiation and metabolism, we evaluated the effect of M2 to M1 macrophage polarization in lipedema using the selective PI3Kγ inhibitor IPI-549. Surprisingly, the differentiation of adipose tissue-derived stem cells with conditioned medium from IPI-549 treated SVF resulted in a significant decreased accumulation of lipids in lipedema versus control SVF. In conclusion, our results indicate that CD163+ macrophages are a critical component in lipedema and re-polarization of lipedema macrophages can normalize the differentiation of adipose-derived stem cells in vitro evaluated by the cellular lipid accumulation. These data open a new chapter in understanding lipedema pathophysiology and may indicate potential treatment options.

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).

Socio-economic position is a well-established driver of health status in the United Kingdom. However, less is known about the reverse relationship — the effect health conditions have on socio-economic position and social mobility. The purpose of this qualitative study was to explore individual experiences and perceptions of the relationship between ill-health and social mobility amongst people with long-term physical health conditions. Structured, in-depth interviews or focus group discussions were conducted with 37 people with long-term physical health conditions (including asthma, cancer, diabetes, heart disease, back pain, arthritis and lipoedema) between November 2019 and January 2020. Participants were asked about the impact of physical health on their career, education, and social life. Factors affecting their ability to cope with their condition were also explored. Participants reported their conditions had been a barrier to upward, and a facilitator of downward social mobility. Physical health conditions were commonly reported to have affected the participants’ educational attainment, choice of occupation, financial stability, and retirement age. Participants also described a lack of understanding from employers about their conditions, with some experiencing instances of discrimination. Factors that reduced the extent to which their condition affects social mobility included, a feeling of control over their condition, support from their employers and knowledge of the available support systems. Individual experience, psychological make-up, and early-life experience also mediated the impact. Participants described clear regional differences in terms of access to services. Advice and support services were often filled by charitable organisations. In conclusion, physical ill-health was reported to have a substantial downward impact on social mobility; by negatively impacting a person's education, choice of occupation and earning ability. Key changes that may enable people to better manage their condition and its impact on social mobility include, improved training of and support from employers and better and consistent access to multi-disciplinary support services from the health and social care system.

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.

Lipoedema is a chronic disease in adipose tissue that almost exclusively affects women during periods of hormonal alterations. Its main symptoms include an abnormal accumulation of subcutaneous fat in the buttock, hips, and legs, which is associated with pain, swelling, and easy bruising. Herein, a grading in three stages is used to determine disease progression. Problematically, lipoedema manifestations are often confused with lifestyle-induced obesity, which is why the various health problems among affected women often remain unrecognized. Overall, research on lipoedema is scarce. As such, this study examined the health, health-related quality of life (HRQOL), and sense of coherence (SOC) among women with lipoedema.

BackgroundThere are both conservative and surgical treatment options for Lipohyperplasia dolorosa (LiDo). A procedure that has been established since 1997 is the surgical treatment through Lymphological Liposculpture according to Cornely™.AimAfter extensive suctioning of the extremities, an extensive subcutaneous wound cavity with a trabecular connective tissue scaffold remains. Nevertheless, surgery-related complications are rare. Postoperative management and administration of antibiotics and antithrombotics are reviewed. The therapies for complications are presented in detail.Materials and methodsRetrospectively, the frequencies of adverse events in 1400 LiDo surgeries in 2020 were evaluated. The mean age of the patients was 47.81 years (range 16–78 years). Symmetrically, 504 outer legs (outer half of the limb [BO]), 504 inner legs (inner half of the limb [BI]), and 392 arms [A] were surgically treated.ResultsRelevant adverse events rarely occurred: infections (1.79%), seromas (0.79%), erysipelas (0.28%), necrosis (0.14%) and deep vein thrombosis (0.07).DiscussionWe were able to reduce the rate of postoperative complications to 3.07% in the Lymphological Liposculpture™ regime for the surgical treatment of LiDo. In their meta-analysis on liposuction, Kanapathy et al. reported an overall incidence of major surgical complications of 3.35%. The overall incidence of minor surgical complications was 11.62%, with seroma (5.51%) being the most common minor complication [26]. Kruppa et al. report that the liposuction procedure including fat removal for esthetic reasons has a complication rate of 9.5%. Wound infections with 4.5% and the formation of erysipelas with 4% are clearly in the foreground [20].

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.

Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) was performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. The top SNP rs1409440 (ORmeta ≈ 2.01, Pmeta ≈ 4 x 10–6) is located upstream of LHFPL6, which is thought to be involved with lipoma formation. Exactly how this relates to lipoedema is not yet understood. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.

BACKGROUND: The aim of this study was to define outcomes after total knee arthroplasty (TKA) in lymphoedema and lipoedema patients managed by a multidisciplinary team and daily compression bandaging. METHODS: A retrospective study was performed in a single centre. Between 2007 and 2018, 36 TKA procedures were performed on 28 consecutive patients with a diagnosis of lymphoedema and lipoedema. Oxford Knee Scores (OKS), EuroQol-5D (EQ-5D) scores, satisfaction scores, radiographs, and complications were obtained at the final follow-up. Patients were admitted to the hospital up to two weeks prior to surgery and remained on the ward for daily compression bandaging by the specialist lymphoedema team. RESULTS: Over the study period, 36 TKAs were performed on 28 patients (5 males, 23 females) with a mean age of 71 years (range 54-90). Of these, 30 TKAs were in patients with lymphoedema, five with lipoedema, and one with a dual diagnosis. Overall, 28 TKAs (21 patients) were available at the final follow-up with a mean follow-up time of 61 months (range 9-138). The mean BMI was 38.5 kg/m2. The mean pre-operative and post-operative Oxford Knee Score increased from 18 (range 2-38) to 29 (range 10-54); p < 0.001. EQ-5D score increased from 0.48 (range 0.15-0.80) to 0.74 (0.34-1.00) (p < 0.001). Mean post-operative satisfaction was 7.6/10 (range 2-10), with 89.3% TKAs satisfied. Complications were one (4%, 1/28) deep vein thrombosis, one superficial wound infection, one prosthetic joint infection, one stiff knee requiring manipulation, and one intra-operative femoral fracture. CONCLUSIONS: Lymphoedema and lipoedema should not be seen as barriers to TKA if adopting a multidisciplinary approach.

Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body distribution in the skin would be lipedema stage-dependent, and could, thus, serve to objectively characterize neuropathic pain in lipedema. The pain was assessed by questionnaire and peripheral cutaneous mechanical sensitization (von-Frey) in lipedema (n = 27) and control (n = 23) consenting female volunteers. Dermal biopsies from (n = 11) Stages 1–3 lipedema and control (n = 10) participants were characterized for neuronal cell body and nociceptive neuropeptide calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) distribution. Stage 2 or 3 lipedema participants responded positively to von Frey sensitization in the calf and thigh, and Stage 3 participants also responded in the arm. Lipedema abdominal skin displayed reduced Tuj-1+ neuronal cell body density, compared to healthy controls, while CGRP and NGF was significantly elevated in Stage 3 lipedema tissues. Together, dermal neuronal cell body loss is consistent with hyper-sensitization in patients with lipedema. Further study of neuropathic pain in lipedema may elucidate underlying disease mechanisms and inform lipedema clinical management and treatment impact.