Lipedema World Alliance Delphi Consensus-Based Position Paper on the Definition and Management of Lipedema: Results from the 2023 Lipedema World Congress in Potsdam

Domain: biology
Published: 2026-01-10
Editorial outcome: minor_revision

Abstract
Lipedema predominantly affects women and is characterized by an abnormal distribution of adipose tissue, accompanied by pain or discomfort in affected areas. Despite growing awareness, inconsistent diagnostic criteria and treatment approaches hinder medical care and research. This multi-phase Delphi study was conducted to address the need for internationally accepted consensus on fundamental aspects of the disease. Through online surveys and in-person discussions, experts representing 19 countries evaluated on 62 original statements regarding (1) clarity, (2) agreement, (3) recommendation for inclusion, (4) strength of evidence, and (5) whether additional evidence was needed. Ultimately, 59 statements reached consensus across eight domains encompassing the definition and management of lipedema. The findings provide a framework to guide internationally applicable recommendations for patients with lipedema that may improve outcomes globally. Limited evidence in several areas highlights the importance of further research, standardization of data reporting, and international collaboration among healthcare providers, researchers, and patient advocates to address this women’s health disparity effectively.

Introduction
Lipedema was first described in the 1940s by Drs. Allen and Hines at the Mayo Clinic, who identified it as a clinical syndrome characterized by abnormal and symmetrical accumulation of fat in the lower extremities of women, frequently accompanied by physical ache, feet sparing orthostatic edema, and psychological distress1. For decades, lipedema was not widely recognized and was often confused with obesity or lymphedema, leading to misdiagnosis and inadequate treatment2. Depending on the availability of healthcare professionals and services for affected individuals within various healthcare systems, lipedema remains underdiagnosed today, with a limited understanding continuing within the medical community. In recent years, however, awareness of lipedema as a distinct clinical entity has increased. This improved disease recognition has been driven by a combination of patient advocacy, research, and clinical interest, prompting the development of national guidelines and consensus documents aimed at improving diagnosis and management3–10.

Despite these advances, however, variability in diagnostic criteria and treatment approaches persists. The lack of standardized diagnostic criteria not only hinders early detection but also complicates research efforts and the development of evidence-based therapies11. There is therefore an urgent need for a unified, internationally accepted consensus on the fundamental aspects of the disease entity and management approaches to caring for patients with lipedema.

This multi-step Delphi consensus study was conducted to address the need for a standardized definition and management approaches to lipedema. By leveraging the collective expertise of clinicians, researchers, and patient representatives from around the world, 59 statements were ultimately recommended for inclusion and reached consensus across eight domains: 36 reached 90–100% agreement, 17 reached 80–90% agreement, and 6 reached 70% agreement. This position paper aims to advance consensus on a standardized, globally relevant definition of lipedema and to delineate principles for its evidence-based management, integrating both empirical data and expert clinical insight. In addition, where evidence was found to be insufficient, further research is called for to improve the lives of individuals with lipedema.

Results
Overall results of Delphi process
After three online Delphi rounds, 59 statements on the definition and management of lipedema reached consensus according to the predefined 70 percent agreement threshold on criterion (ii) and (iii). Thirty-six statements reached 90–100% agreement, seventeen statements reached 80–90% agreement, and six statements reached 70% agreement (Table 1).

In the final Delphi evaluation round 3, 71 out of 103 founding members of the LWA participated (34 female, 37 male), representing 19 countries across 5 continents (Table 2). The majority of respondents reported having extensive experience in working with patients with lipedema (Table 3). The professional backgrounds of the participants were diverse, encompassing medical management, conservative and surgical treatment providers, as well as researchers and patient advocates (Table 4). Patient advocates from seven countries participated, with most (ten of twelve) originating from European nations.

Domain 1: Definition & Leading Symptoms
Statement 1: “Lipedema is a chronic disease”
Clarity of statement 100.0%
Level of agreement 94.4%
Inclusion Rating 93.0%
Strength of Evidence 72.9%
Additional Evidence Needed 28.2%
Expert Panel Comment:
The definition of ‘chronic’ disease varies but typically encompasses conditions that (1) have complex etiology, (2) persist for three months or longer, (3) require ongoing medical management, and (4) may be associated with functional impairment or significantly impact daily activities12. Patients with lipedema typically report long courses of the disease and symptoms that last many years before diagnosis or initiation of appropriate therapeutic measures9,10,13–16. However, systematic longitudinal studies on the chronicity of the disease are not yet available.

Statement 2: “Untreated lipedema typically presents as symmetrical, bilateral enlargement of subcutaneous adipose tissue in the extremities, accompanied by pain and/or discomfort”.
Clarity of statement 90.0%
Level of agreement 88.6%
Inclusion Rating 91.3%
Strength of Evidence 76.8%
Additional Evidence Needed 33.8%
Expert Panel Comment:
The characteristic presentation of lipedema as symmetrical and bilateral enlargement of subcutaneous adipose tissue (SAT) in the extremities is well-documented in the clinical literature1,17,18. The existing literature consistently describes the unique distribution of SAT predominantly in the legs, typically sparing the feet1, and contributing to the characteristic “column-like” appearance. However, it is important to note that variations in clinical presentation exist, and that some patients may demonstrate asymmetry as the disease progresses or in the presence of comorbidities16,19.
Pain in lipedema is a common and often debilitating symptom, significantly impacting patients’ quality of life. The presence of pain varies widely among individuals, ranging from mild discomfort to severe, chronic pain. It typically manifests as a dull, aching sensation in the affected areas, exacerbated by prolonged standing or walking. In addition, patients may experience tenderness to touch and increased sensitivity in the affected regions20–25. More research into the nature of pain and discomfort in lipedema is needed to support disease diagnosis and mechanisms for potential interventions.

Statement 3: “Lipedema is characterized by a disproportional expansion of the subcutaneous adipose tissue of the extremities compared to that in the torso”.
Clarity of statement 91.0%
Level of agreement 89.6%
Inclusion Rating 89.6%
Strength of Evidence 71.9%
Additional Evidence Needed 37.9%
Expert Panel Comment:
In the absence of comorbid conditions, the characteristic lipedema phenotype is recognized for its hallmark feature of disproportionate fat accumulation in the SAT of the extremities compared to that in the torso. Imaging studies have consistently demonstrated increased fat deposition in the legs, supporting the assertion of disproportionate adipose tissue expansion26–32. However, inconsistent terminology for anatomical regions in the literature necessitates clarification in order to more clearly discuss the regions affected by lipedema. In this context, the extremities include the shoulder girdle (Cingulum membri superioris) together with the free upper limbs (Pars libera membri superioris) and the pelvic girdle (Cingulum membri inferioris) together with the free lower limbs (Pars libera membri inferioris). The torso or trunk in this context refer to the central part of the body, including the head and neck region, thorax, abdomen and pelvis33,34.

Statement 4: “Lipedema can involve excess adipose tissue deposition in the upper extremities in asymmetrical and bilateral distribution”.
Clarity of statement 94.1%
Level of agreement 94.0%
Inclusion Rating 89.4%
Strength of Evidence 67.6%
Additional Evidence Needed 28.4%
Expert Panel Comment:
The involvement of the upper extremities (as defined in the “expert panel comment” of statement 3) in lipedema has been observed in both early and advanced stages of the disease. Studies report varying percentages of lipedema patients with arm involvement, ranging from 30% to 80%13,16,19,35.

Statement 5: “Lipedema typically spares hands and feet of excess fat deposition”.
Clarity of statement 97.0%
Level of agreement 90.9%
Inclusion Rating 92.5%
Strength of Evidence 73.5%
Additional Evidence Needed 30.8%
Expert Panel Comment:
According to the original publication of Allen and Hines, lipedema adipose tissue deposition “usually does not involve the feet”1. Recent publications defining diagnostic criteria for lipedema also confirm this for the arms and often describe a separation between normal and abnormal tissue (“Cuff”) at the ankle or wrist4–6,8–10,35. However, although not constituting definitive evidence, patient reports suggest that lipedema-related symptoms may manifest in hands and feet as the disease progresses or in the presence of comorbidities16,19.

Statement 6: “Physical sensitivity to pressure and/or stretch is observed by methods such as palpation, and is mainly reported by patients as pain”.
Clarity of statement 98.5%
Level of agreement 97.0%
Inclusion Rating 98.5%
Strength of Evidence 58.2%
Additional Evidence Needed 40.3%
Expert Panel Comment:
According to the International Association for the Study of Pain (ISAP), pain is defined as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage36. Pain in response to typically innocuous stimuli (such as pressure, palpation, or stretching applied to lipedema-affected tissue) is a central symptom of lipedema, occurring both superficially and subcutaneously, predominantly throughout the legs or arms. Despite its significance, the literature lacks sufficient investigation and characterization of lipedema-related pain, making it complex and challenging to define23,25,37. The precise pathogenesis of pain in lipedema remains uncertain, with proposed mechanisms including central sensitization, nociceptive pain, and autonomic peripheral neuropathies20,21.

Statement 7: “Increased sensitivity and pain caused by lipedema seem to be restricted to the body areas with lipedema-related volume increase”.
Clarity of statement 92.6%
Level of agreement 85.3%
Inclusion Rating 83.6%
Strength of Evidence 55.2%
Additional Evidence Needed 39.4%
Expert Panel Comment:
The clinical symptoms of lipedema typically manifest in the areas affected by the enlargement of SAT25,37–39. As outlined in statements 2−5, this manifestation is typically confined to the extremities, excluding the hands and feet. However, although not constituting definitive evidence, patient reports suggest that lipedema-related symptoms may be present in other body regions as the disease progresses or in the presence of comorbidities16.

Statement 8: “Patients often report swelling or heaviness in affected areas”.
Clarity of statement 92.6%
Level of agreement 89.7%
Inclusion Rating 88.2%
Strength of Evidence 54.4%
Additional Evidence Needed 36.8%
Expert Panel Comment:
Patients with lipedema frequently describe the affected areas to exert a feeling of swelling or a sensation of heaviness40. Incidence data regarding these symptoms are limited in their availability16.

Statement 9: “Pitting edema is usually not present in lipedema-affected tissue”.
Clarity of statement 91.2%
Level of agreement 89.7%
Inclusion Rating 86.8%
Strength of Evidence 50.0%
Additional Evidence Needed 44.1%
Expert Panel Comment:
Existing clinical evidence supports the assertion that, in the absence of comorbid conditions, pitting edema is generally absent in lipedema-affected tissue. In this regard, lipedema differs significantly from lymphedema41. As in the rest of the population, some individuals with lipedema may present with lymphedema, however, it is unknown whether this secondary condition represents primary or secondary lymphedema. Regardless, a causative role in lipedema has not been established.

Statement 10: “Patients with lipedema often experience easy bruising in affected areas”.
Clarity of statement 95.5%
Level of agreement 94.0%
Inclusion Rating 92.5%
Strength of Evidence 58.2%
Additional Evidence Needed 35.8%
Expert Panel Comment:
A frequently reported symptom of patients with lipedema is a tendency to bruise without recollection of preceding trauma within the affected areas, without bleeding from other sites, and in the absence of systemic disorders known to result in bruising. Availability of incidence data is limited, with up to 90.6% of patients reporting easy bruising.16,40,42,43. However, it is important to note that easy bruising is not pathognomonic for lipedema and can have various etiologies.

Statement 11: “Kaposi-Stemmer’s sign is usually negative in lipedema”.
Clarity of statement 93.9%
Level of agreement 95.5%
Inclusion Rating 95.4%
Strength of Evidence 71.6%
Additional Evidence Needed 22.7%
Expert Panel Comment:
Kaposi-Stemmer’s sign, a clinical indicator of lymphedema characterized by the inability to pinch a fold of skin at the base of the second toe or second finger44,45, is typically considered negative in lipedema46. If there is lymphostasis in addition to lipedema, the sign may be positive.

Domain 2: Pathophysiology
Statement 12: “Lipedema is a disease involving subcutaneous adipose tissue”.
Clarity of statement 92.4%
Level of agreement 94.0%
Inclusion Rating 90.9%
Strength of Evidence 78.8%
Additional Evidence Needed 19.4%
Expert Panel Comment:
Adipose tissue, commonly known as fat, is a type of connective tissue that consists of lipid-filled cells (adipocytes) surrounded by a matrix of collagen fibers, blood vessels, fibroblasts, and immune cells47. Lipedema has been reported to affect components of the SAT32,38,39,48–56.

Statement 13: “Numerous findings suggest that inflammation may contribute to the pathogenesis of lipedema”.
Clarity of statement 95.2%
Level of agreement 87.7%
Inclusion Rating 83.1%
Strength of Evidence 49.2%
Additional Evidence Needed 60.9%
Expert Panel Comment:
Studies have proposed that inflammatory processes may play a role in the development and progression of lipedema39,48,49,51,53,54,56,57. Nevertheless, it is crucial to note that the exact nature and extent of inflammation25 in lipedema remain areas of active investigation, and the mechanistic underpinnings are not fully elucidated. In particular, it remains unclear whether the observed tissue inflammation is a cause or a consequence of lipedema.

Statement 14: “Numerous findings suggest that hormonal factors may contribute to the pathogenesis of lipedema”.
Clarity of statement 96.8%
Level of agreement 96.9%
Inclusion Rating 92.1%
Strength of Evidence 58.1%
Additional Evidence Needed 56.3%
Expert Panel Comment:
Hormonal factors are considered to contribute to the regulation of lipedema pathogenesis58–60 as lipedema symptoms are reported to worsen during hormonal shifts16. Nevertheless, it is important to emphasize that precise pathophysiological mechanisms for conclusively linking hormonal factors to lipedema have not yet been fully elucidated58,61,62.

Statement 15: “Several findings suggest that extracellular fluid volume might be elevated in lipedema-affected tissue compared to BMI-matched unaffected controls”.
Clarity of statement 87.1%
Level of agreement 76.2%
Inclusion Rating 72.6%
Strength of Evidence 46.8%
Additional Evidence Needed 66.1%
Expert Panel Comment:
Histological analysis63, bioimpedance spectroscopy64,65, in-vivo MRI imaging27,66, and near-infrared fluorescent lymphatic imaging67 indicate that lipedema might be characterized by an accumulation of excess extracellular fluid (ECF), possibly deriving from impaired capillaries or dysfunctionally lymphatic vessels. Notably, clinical observation generally does not reveal visible edema in individuals with lipedema. A hypothesis has been postulated, suggesting that the absence of edema, despite an elevation in ECF, may be attributed to an increase in glycosaminoglycans and proteoglycans, which would bind the increased ECF8.

Domain 3: Epidemiology
Statement 16: “Lipedema primarily affects biological females. Occurrence in biological males appears to be possible but rare”.
Clarity of statement 96.7%
Level of agreement 88.7%
Inclusion Rating 88.9%
Strength of Evidence 69.8%
Additional Evidence Needed 33.9%
Expert Panel Comment:
The prevailing understanding is that lipedema predominantly manifests in biological females. Limited case reports suggest the occurrence of lipedema in biological males, with cases frequently associated with hormonal abnormalities68–72. Additional research is warranted to explore the underlying factors contributing to this disparity.

Statement 17: “Hormonal changes may trigger or exacerbate the symptoms of lipedema”.
Clarity of statement 100.0%
Level of agreement 98.4%
Inclusion Rating 98.4%
Strength of Evidence 63.9%
Additional Evidence Needed 36.5%
Expert Panel Comment:
Phases characterized by hormonal fluctuations, such as puberty, pregnancy, or menopause, are frequently temporally associated with the onset or exacerbation of lipedema symptoms16,73. The causality of hormonal changes and their potential to have an impact on lipedema symptoms58,59, including the influence of other hormonal stimuli (such as hormone replacement therapy, contraceptives, etc.), remains uncertain15. Therefore, more comprehensive research, including longitudinal studies and investigations into the underlying biological mechanisms, is needed to establish a clearer understanding of the relationship between hormonal changes and lipedema.

Statement 18: “Lipedema is hereditary in some cases”.
Clarity of statement 96.8%
Level of agreement 88.7%
Inclusion Rating 88.9%
Strength of Evidence 63.9%
Additional Evidence Needed 47.5%
Expert Panel Comment:
A frequently observed positive family history, with prevalence ranging from 30% to 90%13,42,73–76, indicates a hereditary nature of lipedema. An examination of familial clusters of lipedema patients has proposed an X-linked dominant inheritance pattern or, more likely, an autosomal dominant inheritance with sex restriction of a single dominant gene77. In addition, other studies have postulated an oligogenic inheritance model, suggesting the involvement of multiple gene variants associated with the phenotypic presentation of lipedema78–84. It is plausible that lipedema may manifest as either a primary type or as part of a syndromic hereditary condition79.

Statement 19: “The prevalence of lipedema in the adult female population remains unknown. Estimates range from less than 1% to up to 12%”.
Clarity of statement 96.8%
Level of agreement 79.0%
Inclusion Rating 83.9%
Strength of Evidence 37.1%
Additional Evidence Needed 66.1%
Expert Panel Comment:
Accurately establishing the prevalence of lipedema presents a notable challenge owing to inconsistencies in diagnostic criteria, limited awareness among healthcare professionals and patients, variations in study populations (whether drawn from the general population or specialized institutions), geographical disparities, and differing methodological approaches. Current estimates within the adult female population underscore the considerable variability observed in reported figures18,73,76,77,85–91.

Domain 4: Comorbidities & concomitant diseases
Statement 20: “Obesity is a frequently observed concomitant disease in patients with lipedema”.
Clarity of statement 98.4%
Level of agreement 87.3%
Inclusion Rating 92.1%
Strength of Evidence 62.9%
Additional Evidence Needed 44.4%
Expert Panel Comment:
Lipedema is often either misdiagnosed as or coexists with obesity, posing challenges in accurate differentiation. Research consistently demonstrates a higher prevalence of obesity among individuals with lipedema compared to the general population, as assessed by BMI13,40,77,92–94. However, BMI is not an ideal tool to assess obesity in patients with lipedema due to the disproportionate body habitus inherent in lipedema95, potentially contributing to divergent clinical evaluations and interpretations of existing literature. Nevertheless, when both conditions coexist, appropriate treatment must be provided for each as a separate disease. In addition, it is essential to recognize that the presence of obesity in lipedema patients may exacerbates symptoms and complicate management strategies. While the precise nature of the relationship between lipedema and obesity warrants further investigation, the recognition of this frequent concomitance is crucial for informing holistic and patient-centered approaches to care.

Statement 21: “Lipedema is not an obesity-related comorbidity”.
Clarity of statement 98.4%
Level of agreement 92.1%
Inclusion Rating 91.8%
Strength of Evidence 69.4%
Additional Evidence Needed 32.8%
Expert Panel Comment:
Historically, lipedema was often mischaracterized as a simple consequence of obesity. Several studies have demonstrated that lipedema is distinct from obesity and should be regarded as a separate entity to facilitate accurate diagnosis and tailored therapeutic interventions20,96–98. Lipedema adipose tissue exhibits distinct morphological, molecular and metabolic characteristics compared to obesity-type adipose tissue32,99. In other words, lipedema is not an invariable comorbidity with obesity; rather, it may coincide with obesity100.

Statement 22: “Body mass index (BMI) has limited value in distinguishing between lipedema and obesity. Therefore, it is advisable to utilize the Waist-to-Height Ratio (WHtR) to exclude or assess obesity”.
Clarity of statement 93.5%
Level of agreement 73.3%
Inclusion Rating 71.0%
Strength of Evidence 39.3%
Additional Evidence Needed 71.0%
Expert Panel Comment:
The body mass index (BMI) for characterizing obesity is of limited value in lipedema patients, as it leads to falsely high values in the area of overweight or mild obesity due to the increase in adipose tissue in the extremities. Nevertheless, as in all areas of surgery, BMI may have a positive correlation with surgical complication rates. A more accurate assessment of disproportionate fat distribution and metabolic health can be achieved through the waist-to-height ratio (WHtR)95,101–103. However, it is essential to acknowledge that while WHtR may provide valuable insights, further research and consensus development are warranted to establish standardized criteria for its application in distinguishing lipedema from obesity across diverse populations9,10.

Statement 23: “In cases where lipedema coincides with obesity, lipedema symptoms can be expected to persist after bariatric surgery”.
Clarity of statement 91.9%
Level of agreement 88.9%
Inclusion Rating 87.1%
Strength of Evidence 58.7%
Additional Evidence Needed 44.3%
Expert Panel Comment:
Weight loss in patients with lipedema has been reported to reduce leg volume, improve quality of life and alleviate symptoms92,104,105. Conversely, current research indicates that despite significant weight loss achieved through bariatric surgery, symptoms related to lipedema often persist92,100,106–108. Studies suggest that the distinctive pathophysiology of lipedema may play a role in the ongoing persistence of these symptoms. In addition, the reduction in volume of the SAT in lipedema-affected extremities may be less pronounced compared to the trunk.

Statement 24: “Concomitant lymphostasis can develop in lipedema”.
Clarity of statement 90.3%
Level of agreement 88.7%
Inclusion Rating 86.9%
Strength of Evidence 43.5%
Additional Evidence Needed 52.5%
Expert Panel Comment:
Reports suggest that lymphatic impairment leading to lymphostasis or lymphedema may co-occur at any stage of lipedema, further complicating the clinical presentation. The use of multiple modalities to assess lymphatic dysfunction in lipedema is ongoing, as well as the etiology of observed differences27,66,67,109,110. Without definitive evidence supporting a primary lymphatic dysfunction in lipedema, lymphostasis may be related to an imbalance in the production and removal of lymphatic fluid, causing a capacity overload (high-volume transport insufficiency, “Marsch thesis”111) as lymphoscintigraphic findings were not associated to the BMI110,112. Furthermore, lymphostasis may be related to coincident obesity or excessive adipose tissue expansion.

Statement 25: “Several findings suggest that the prevalence of hypothyroidism might be higher in lipedema patients than in non-lipedema populations with comparable BMI and age”.
Clarity of statement 95.2%
Level of agreement 77.4%
Inclusion Rating 77.0%
Strength of Evidence 64.5%
Additional Evidence Needed 41.0%
Expert Panel Comment:
Recent publications highlighted a possible link between lipedema and hypothyroidism13,14,19,90. The demonstrated prevalence, ranging from 19% to 36%, surpasses that of comparable populations, adjusted for sex, age, and BMI(0.5–2.0%)113. However, the extent of a causal connection or whether hypothyroidism is merely an epiphenomenon of coincident obesity remains unclear114.

Statement 26: “Lipedema might be associated with connective tissue disorders, such as hypermobility spectrum disorders”.
Clarity of statement 96.8%
Level of agreement 75.8%
Inclusion Rating 72.6%
Strength of Evidence 37.7%
Additional Evidence Needed 65.6%
Expert Panel Comment:
Evidence suggests that women with lipedema exhibit decreased elasticity in both skin115 and aorta116, along with joint hypermobility16,117,118 and muscle weakness119. There is speculation about a link between lipedema and connective tissue disorders, specifically hypermobility spectrum disorders (HSD), although no conclusive underlying mechanism has been identified120. Considering the inconsistency of HSD in lipedema, a hypothesis has proposed categorizing it as a subtype (“rusticanus Moncorps type”) of lipedema115. Further investigation is needed to confirm a definitive association between lipedema and HSD.

Domain 5: Impact on Quality of Life and Symptom Burden
Statement 27: “Lipedema can negatively impact mental health and overall quality of life”.
Clarity of statement 100.0%
Level of agreement 98.4%
Inclusion Rating 98.4%
Strength of Evidence 70.5%
Additional Evidence Needed 38.7%
Expert Panel Comment:
The available literature consistently highlights the significant psychosocial burden associated with lipedema, emphasizing its adverse effects on mental health and overall quality of life94,121–123. The psychosocial implications of lipedema are multifaceted, encompassing impaired daily functioning, social withdrawal, and body image dissatisfaction124,125. Further evidence is required to elucidate how quality of life is affected across broader health domains and in diverse cultural contexts, as the psychosocial burden is exacerbated by insufficient support for affected individuals within many healthcare systems.

Statement 28: “If present, psychological involvement may be caused by lipedema-related symptoms rather than being the cause of those symptoms”.
Clarity of statement 93.4%
Level of agreement 90.2%
Inclusion Rating 85.5%
Strength of Evidence 48.4%
Additional Evidence Needed 53.2%
Expert Panel Comment:
The intricate interplay between psychological factors and the symptomatology of lipedema has garnered attention123,126. Existing literature suggests that the psychological burden experienced by individuals with lipedema may be a result of the challenges posed by the physical aspects and functional limitations associated with the disease. Conversely, psychological distress (e.g., after traumatic experiences) can potentially exacerbate symptomatology or influence coping mechanisms. Therefore, the relationship between psychological factors and lipedema is complex and warrants careful consideration.

Statement 29: “Missed or delayed diagnosis or management of lipedema negatively affects a patient’s symptom burden, mental well-being, and overall quality of life”.
Clarity of statement 100.0%
Level of agreement 100.0%
Inclusion Rating 100.0%
Strength of Evidence 67.7%
Additional Evidence Needed 31.1%
Expert Panel Comment:
Lipedema may not consistently progress, yet certain factors, such as overall weight gain42 and hormonal changes (e.g., during pregnancy), can contribute to long-term symptom exacerbation. A progression of the disease, marked by increased pain and disproportionate adipose tissue accumulation, along with unsuccessful therapeutic interventions and diets, heightens the risk of developing depression and has a significant impact on the overall quality of life15,94,121. Therefore, it is advisable to pursue early diagnosis and implement timely treatment interventions127.

Statement 30: “Missed or delayed diagnosis or management of lipedema increases the cost burden for patients and the healthcare system”.
Clarity of statement 100.0%
Level of agreement 93.3%
Inclusion Rating 91.8%
Strength of Evidence 57.4%
Additional Evidence Needed 49.2%
Expert Panel Comment:
The economic impact of delayed diagnosis and suboptimal management in lipedema is a multifaceted concern, affecting both patients and the broader healthcare system. Research suggests that the complex nature and the fact that the condition is often overlooked contribute to delayed diagnosis, leading in turn to a protracted period of untreated symptoms15. This delay can result in increased healthcare utilization and costs due to the progression of the disease and the development of associated comorbidities13. Furthermore, the economic burden extends beyond direct medical costs, also encompassing expenses related to productivity loss, disability, and diminished quality of life122.

Domain 6: Diagnostic approach
Statement 31: “The clinical diagnosis of lipedema relies on the patient’s medical history, physical examination and exclusion of differential diagnoses”.
Clarity of statement 98.4%
Level of agreement 98.4%
Inclusion Rating 98.4%
Strength of Evidence 72.1%
Additional Evidence Needed 53.2%
Expert Panel Comment:
Accurate diagnosis of lipedema remains challenging due to its overlapping clinical features with other adipose tissue disorders and lymphatic conditions128. The reliance on comprehensive evaluation, including detailed medical history, thorough physical examination, and exclusion of differential diagnoses, underscores the complexity of diagnosing lipedema in clinical practice4,8,9,46. Notably, the absence of definitive diagnostic criteria and standardized assessment tools may contribute to delays in diagnosis and misidentification of the disease. Collaborative efforts are needed to establish consensus guidelines and improve diagnostic accuracy for the benefit of patients and healthcare providers.

Statement 32: “Currently, no imaging, serological or genetic tests, or clinical measurement instruments, are officially approved to verify the clinical diagnosis”.
Clarity of statement 98.4%
Level of agreement 93.5%
Inclusion Rating 91.8%
Strength of Evidence 66.1%
Additional Evidence Needed 39.3%
Expert Panel Comment:
Research efforts on different diagnostic modalities are underway to aid the clinical diagnosis of lipedema, including imaging, genetic, serologic, and bedside techniques20,25,38,120,129–131. While these investigations show promise in enhancing diagnostic precision and differentiating from other conditions, it is crucial to acknowledge the current lack of official approval for any specific modality in verifying the clinical diagnosis of lipedema.

Statement 33: “Routine clinical exams should include standardized anthropometric measurements, such as waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and body mass index (BMI)”.
Clarity of statement 96.7%
Level of agreement 82.3%
Inclusion Rating 75.8%
Strength of Evidence 57.4%
Additional Evidence Needed 43.3%
Expert Panel Comment:
Although anthropometric measurements, including WHtR, WHR, and BMI, taken individually are not useful for diagnosing lipedema, taken together, they are essential in the assessment of overall health and are widely employed in routine clinical examinations132. Despite its limited significance in lipedema133, BMI can support disease monitoring due to its simplicity in measurement and interpretation. While BMI does not reflect regional fat distribution, WHR is subject to age, sex, and ethnic variations. Conversely, WHtR has been identified as a valuable predictor of cardiometabolic risk, with studies suggesting its superiority over other indices, particularly in assessing central obesity95,103,134,135.

Statement 34: “The clinical classification of lipedema into stages does not reflect the complete symptom severity”.
Clarity of statement 96.7%
Level of agreement 95.1%
Inclusion Rating 93.4%
Strength of Evidence 60.7%
Additional Evidence Needed 52.5%
Expert Panel Comment:
The current clinical stage classification of lipedema is based on the severity of palpation findings in the skin and subcutaneous tissue136. Palpable alterations correspond to a progressive enlargement of nodular and fibrotic tissue structures39, accompanied by an increasing induration of the skin and subcutaneous tissue. While the current staging system primarily focuses on anatomical aspects, it does not adequately correlate with the nuanced and multifaceted nature of symptom severity in individuals with lipedema137.

Statement 35: “The current clinical classification for lipedema into stages has limited relevance for the disease management”.
Clarity of statement 100.0%
Level of agreement 91.9%
Inclusion Rating 90.3%
Strength of Evidence 54.1%
Additional Evidence Needed 49.2%
Expert Panel Comment:
The existing clinical classification of lipedema into stages does not reflect the individual differences in the total perceived discomfort due to lipedema, presenting challenges in guiding optimal disease management9,10. While stages have been suggested based on phenotypic characteristics and palpation findings136, the practical utility of this classification in guiding therapeutic strategies is limited. To achieve a more nuanced and comprehensive approach to disease management, considerations should extend to factors such as pain intensity, quality of life, and functional impairment98,137.

Statement 36: “A progression in the severity of lipedema-associated symptoms depends on various factors and is not universal”.
Clarity of statement 93.4%
Level of agreement 95.1%
Inclusion Rating 95.1%
Strength of Evidence 47.5%
Additional Evidence Needed 57.4%
Expert Panel Comment:
The trajectory of lipedema presents considerable heterogeneity, with varying degrees of symptom severity influenced by a complex interplay of factors. While some individuals may experience a progression in symptom severity over time, others may exhibit stable or fluctuating symptomatology. Existing literature suggests that factors such as hormonal changes, individual predisposition, overall weight gain42 and lifestyle factors may contribute to the diversity in symptom progression85. However, it is essential to acknowledge the limited availability of long-term, prospective studies that comprehensively explore the multitude of factors influencing the natural history and disease course of lipedema.

Statement 37: “The excess limb volume in lipedema is generally not associated with obesity”.
Clarity of statement 93.2%
Level of agreement 79.7%
Inclusion Rating 76.3%
Strength of Evidence 39.0%
Additional Evidence Needed 52.5%
Expert Panel Comment:
The relationship between excess limb volume in lipedema and obesity is a complex and much-debated aspect within the current literature. While some authors suggest that limb volume increase in lipedema is not necessarily correlated with overall obesity100, others propose a potential overlap between lipedema and obesity9,10, indicating that the two conditions may coexist or influence each other. Given the high number of patients with lipedema who also suffer from concomitant obesity, excess limb volume can be attributed to both underlying conditions. The lack of a universally accepted definition for obesity in the context of lipedema and the varied methodologies used to assess limb volume and obesity contribute to the ongoing discourse. Further research and standardized criteria are warranted to elucidate the intricate interplay between limb volume excess in lipedema and obesity.

Statement 38: “The clinical classifications based on localization have only descriptive significance”.
Clarity of statement 95.1%
Level of agreement 88.5%
Inclusion Rating 86.9%
Strength of Evidence 39.3%
Additional Evidence Needed 43.3%
Expert Panel Comment:
While localization-based phenotype classifications (such as subtypes according to Meier-Vollrath138 or form variant according to Herpertz139) provide a useful framework for characterizing the distribution of adipose tissue in lipedema117,138,139, their clinical utility in predicting disease progression, response to treatments, or specific complications remains limited. Nevertheless, localization-based phenotype classifications serve as a descriptive tool facilitating the contextualization of clinical cases among experts, thus retaining their practical significance. Further research is needed to elucidate the practical implications and prognostic value of these classification systems, taking into account the heterogeneity observed in patients with lipedema.

Domain 7: Treatment modalities
Statement 39: “All therapeutic interventions of lipedema aim at alleviating symptoms and preventing or delaying progression”.
Clarity of statement 95.1%
Level of agreement 90.2%
Inclusion Rating 90.2%
Strength of Evidence 55.7%
Additional Evidence Needed 45.8%
Expert Panel Comment:
Current therapeutic interventions for lipedema primarily focus on (1) symptom management and (2) disease progression prevention, rather than curative measures9,46,97. It is crucial to note that while existing treatment modalities for lipedema can provide meaningful symptom relief, they do not eliminate the underlying pathology of lipedema altogether.

Statement 40: “Comprehensive disease management requires a multidisciplinary approach tailored to individual needs, which often may involve physicians, physical therapists, dietitians, and mental health professionals”.
Clarity of statement 96.7%
Level of agreement 96.7%
Inclusion Rating 96.7%
Strength of Evidence 63.9%
Additional Evidence Needed 41.7%
Expert Panel Comment:
The significance of a multidisciplinary approach in the comprehensive management of complex conditions, such as lipedema, is widely acknowledged in the literature140. Collaboration among different health care professionals is vital to address the diverse aspects of the disease, encompassing medical, rehabilitative, nutritional, and psychological dimensions. While there is a growing consensus on the importance of multidisciplinary care, further research is warranted to establish standardized protocols and assess the long-term effectiveness of such collaborative interventions in lipedema management.

Statement 41: “Lipedema pain and physical sensitivity in lipedema-affected areas have been reported to be reduced by bandaging, compression, complete physical decongestive therapy or other physical therapies (such as shock wave therapy), dietary changes, tailored exercise, and lipedema reduction surgery, with varying effect sizes and durations”.
Clarity of statement 86.7%
Level of agreement 86.9%
Inclusion Rating 83.3%
Strength of Evidence 45.9%
Additional Evidence Needed 65.6%
Expert Panel Comment:
Various interventions show potential for symptom relief in lipedema, but the quality of the supporting evidence is variable. The heterogeneity of study designs, patient populations and diagnostic criteria makes direct comparisons between different treatment modalities challenging. In addition, the duration of therapeutic effects remains a subject of investigation, with some interventions demonstrating sustained benefits over time, while others may necessitate ongoing management. It is important to emphasize that a universally applicable therapeutic regimen for lipedema has yet to be established. The choice of treatment modalities often depends on the individual patient’s characteristics, including disease severity, comorbidities, and personal preferences9.

Statement 42: “Conservative management of lipedema should include lifestyle and nutritional optimization, compression therapy, and exercise to alleviate symptoms and improve quality of life”.
Clarity of statement 95.1%
Level of agreement 93.4%
Inclusion Rating 90.0%
Strength of Evidence 63.3%
Additional Evidence Needed 44.1%
Expert Panel Comment:
Lifestyle and nutritional changes play a pivotal role, aiming to address potential exacerbating factors and enhance overall well-being104,141,142. Compression therapy has demonstrated effectiveness in improving symptoms, contributing to enhanced patient comfort and mobility143–145. Tailored exercise regimes, such as aquatic exercise, are recommended to promote lymphatic flow146 and muscle strength without placing excessive strain on affected limbs145,147. While individual responses to these interventions may vary, a comprehensive strategy incorporating these elements is a cornerstone in the holistic care of lipedema patients.

Statement 43: “Active self-management can help control lipedema-related symptoms and improve the overall quality of life”.
Clarity of statement 95.1%
Level of agreement 91.7%
Inclusion Rating 90.0%
Strength of Evidence 36.1%
Additional Evidence Needed 59.3%
Expert Panel Comment:
Existing literature suggests that active self-management practices play a crucial role in mitigating lipedema-related symptoms and enhancing the overall quality of life for affected individuals9. Patient education and training are critical components of effective self-management. However, it is important to note that the evidence base for specific self-management strategies is still evolving, and further research is needed to establish comprehensive guidelines for effective self-management in lipedema.

Statement 44: “Although Complex (also known as Complete) Decongestive Therapy (CDT) can be an important and effective treatment even for early-stage lipedema, not all components are required for every patient”.
Clarity of statement 95.1%
Level of agreement 86.9%
Inclusion Rating 86.9%
Strength of Evidence 39.3%
Additional Evidence Needed 53.3%
Expert Panel Comment:
The key components of Complex (also known as Complete) Decongestive Therapy (CDT) include (1) compression therapy, (2) manual lymphatic drainage (MLD), (3) decongestive exercise, (4) skin care, and (5) empowerment/self-management. Compression therapy for lipedema aims to reduce pain and alleviate subjective symptoms, especially when combined with physical activity, demonstrating positive effects145,148. There is no evidence supporting the sole use of MLD for therapeutic benefits in lipedema, as it has only been studied in various combination forms with other therapies143,144,149. However, it has been shown to have a sympatholytic effect, increase pain tolerance, and elevate pain thresholds9. Not all lipedema patients may require every component of CDT, and tailoring therapeutic interventions based on the specific needs and characteristics of each patient is crucial.

Statement 45: “Nutritional guidance can help patients manage their weight, optimize overall health, reduce lipedema-associated symptoms and improve their response to therapeutic interventions”.
Clarity of statement 96.7%
Level of agreement 93.4%
Inclusion Rating 93.4%
Strength of Evidence 65.6%
Additional Evidence Needed 47.5%
Expert Panel Comment:
The existing literature suggests that addressing chronic inflammation in lipedema, especially with concomitant obesity, through patient education on pro-inflammatory triggers and recommending an anti-inflammatory Mediterranean or ketogenic diet141,150–158. Elevated insulin levels in both conditions can contribute to lipogenesis and inflammation, emphasizing the importance of a diet that avoids blood glucose and insulin spikes159–161. Limited studies exist on lipedema-specific diets, but reviews highlight the potential benefits of ketogenic diets, including weight reduction, decreased adipose tissue, and symptom relief105,142,162–166. The absence of pro-inflammatory blood glucose spikes in ketogenic diets is proposed to make them more effective in combating lipedema inflammation151.

Statement 46: “Although pathological subcutaneous adipose tissue in lipedema is known to be largely resistant to dietary interventions, addressing overall weight loss in coincident obesity may result in symptom improvement”.
Clarity of statement 95.0%
Level of agreement 93.3%
Inclusion Rating 93.2%
Strength of Evidence 62.1%
Additional Evidence Needed 40.7%
Expert Panel Comment:
Although lipedema SAT is considered largely diet-resistant19, improvements in lipedema-associated symptoms have been demonstrated through a combination of dietary modification, weight reduction and exercise141. Conversely, it has been reported that in patients with coincident obesity, bariatric surgery–induced weight loss and reductions in BMI did not result in significant improvement of lipedema-associated symptoms in the absence of dietary modification100. To promote optimal health and mobility, it is advisable to provide nutritional guidance and, when applicable, engage in obesity therapy aligned with clinical guidelines97.

Statement 47: “Considering that obesity worsens the manifestations of lipedema, disease management should include weight optimization, with a focus on waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR)”.
Clarity of statement 91.8%
Level of agreement 83.3%
Inclusion Rating 80.3%
Strength of Evidence 50.8%
Additional Evidence Needed 51.7%
Expert Panel Comment:
Maintaining a normal weight can help prevent a progression of lipedema-associated symptoms, preserve mobility, and reduce the risk of developing osteoarthritis97. Obesity classification typically relies on BMI132. However, in the context of lipedema and in line with statement 33, utilizing alternative anthropometric measures—such as WHtR—may be more appropriate for assessing or excluding overweight and obesity, particularly in the context of metabolic health categorization95,167.

Statement 48: “Psychological and social support, addressing body image issues, mental well-being, and coping strategies, can be important to address the symptom burden of patients living with lipedema”.
Clarity of statement 96.7%
Level of agreement 98.3%
Inclusion Rating 96.7%
Strength of Evidence 68.3%
Additional Evidence Needed 37.3%
Expert Panel Comment:
Acknowledging the profound impact of lipedema on patients, addressing psychological and social dimensions is vital for comprehensive care. Studies emphasize the multifaceted psychosocial challenges, including impaired daily functioning, social withdrawal, and mental health implications122,123,168. Interventions targeting these aspects have demonstrated efficacy in improving overall well-being and coping mechanisms121,169.

Statement 49: “Tailored exercises, such as physical activity in water, walking, and yoga, can help maintain mobility, address lipedema related symptoms and support weight management in individuals with lipedema”.
Clarity of statement 95.0%
Level of agreement 91.7%
Inclusion Rating 90.2%
Strength of Evidence 56.7%
Additional Evidence Needed 42.6%
Expert Panel Comment:
A growing body of literature underscores the potential benefits of exercise interventions for individuals with lipedema, emphasizing improvements in physical function, mobility, symptom management and quality of life143,144,149,170–172. Specifically, water-based activities have shown promise in reducing pain and enhancing mobility, possibly due to effects and physical properties of water, such as hydrostatic pressure and buoyancy, and consecutively reduced impact on joints147,173,174. Moreover, structured exercise—such as walking and yoga—have been associated with improved muscular strength, and psychological well-being, factors that are particularly relevant for individuals with lipedema119,175,176.

Statement 50: “Currently, there is no evidence for the effectiveness of any pharmacological interventions in treating lipedema”.
Clarity of statement 100.0%
Level of agreement 93.3%
Inclusion Rating 93.2%
Strength of Evidence 58.3%
Additional Evidence Needed 44.1%
Expert Panel Comment:
There is no evidence to support the efficacy of pharmaceutical interventions in alleviating lipedema symptoms. Supplements with potential antioxidative, edema-reducing, or immunomodulatory effects have been explored for managing lipedema symptoms. However, the existing evidence supporting their efficacy is limited151,153,155,156,177–179.

Statement 51: “In cases where lipedema coincides with obesity and metabolic disease, it is advisable to prioritize treatment for obesity before considering lipedema reduction surgery”.
Clarity of statement 100.0%
Level of agreement 93.3%
Inclusion Rating 91.7%
Strength of Evidence 66.7%
Additional Evidence Needed 40.7%
Expert Panel Comment:
The relationship between obesity, metabolic disease, and lipedema is complex, necessitating a nuanced approach to treatment decisions. Existing literature highlights the bidirectional interplay between obesity and lipedema, with obesity potentially exacerbating lipedema symptoms180 and vice versa due to impaired mobility, pain or psychological burden linked to lipedema13,40,172,174,181. While addressing obesity is crucial for overall health, it is essential to recognize that lipedema is a distinct condition with unique pathophysiological features. The sequential or simultaneous management of both conditions may be warranted, acknowledging that successful outcomes often require a multidisciplinary approach9. When considering lipedema reduction surgery, it is generally advisable to address concurrent obesity first182, as a lower BMI correlates with improved outcomes74 and may mitigate perioperative risks183,184. However, in some cases, it may not be universally applicable to postpone lipedema reduction surgery until obesity or metabolic health has been addressed, as the severity of the condition, the patient’s goals and general health may vary from case to case100,185.

Statement 52: “Lymph vessel-sparing lipedema reduction surgery should be considered when there is potential for a positive impact on lipedema-related symptoms”.
Clarity of statement 86.7%
Level of agreement 89.7%
Inclusion Rating 87.9%
Strength of Evidence 58.6%
Additional Evidence Needed 49.2%
Expert Panel Comment:
Although conservative treatment can alleviate lipedema symptoms, it does not achieve long-lasting benefits and cannot prevent the progression of the disease. Lipedema reduction surgery, or liposuction, is currently the only technique for removing abnormal lipedema tissues and slowing a potential progression of the disease. Recent uncontrolled before-and-after studies reported positive results in reducing extremity size and alleviating lipedema-associated symptoms such as spontaneous pain, easy bruising, sensitivity to pressure, impairment in quality of life, restrictions to mobility, edema, sensation of tightness, and overall improvement in patients’ quality of life186–189. However, currently, there is a lack of randomized controlled trials and long-term follow-up studies assessing the clinical effectiveness and safety of lipedema reduction surgery compared to no treatment or alternative approaches in managing lipedema. Ongoing studies have not yet yielded definitive results190,191.

Statement 53: “Surgical interventions should be performed by healthcare providers with extensive knowledge in lipedema management, including conservative treatments, as part of an integral approach”.
Clarity of statement 98.3%
Level of agreement 98.3%
Inclusion Rating 98.3%
Strength of Evidence 53.3%
Additional Evidence Needed 43.1%
Expert Panel Comment:
In contrast to aesthetic liposuctions, the primary goal of lipedema reduction surgery is a medically indicated, functional intervention for symptom reduction through subtotal resection of the presumed pathological, subcutaneous fat tissue in the limbs affected by lipedema. Therefore, lipedema reduction surgery, integrated with conservative management, should be performed according to clinical best practice outlined by medical associations and developed specifically for lipedema4–6,8–10.

Domain 8: Future directions
Statement 54: “Raising awareness about lipedema within the medical community and wider society is essential to reduce misdiagnosis and stigma”.
Clarity of statement 100.0%
Level of agreement 98.3%
Inclusion Rating 96.7%
Strength of Evidence 66.7%
Additional Evidence Needed 30.0%
Expert Panel Comment:
Raising awareness about lipedema is critical for timely diagnosis and management, as patients often experience prolonged diagnostic delays and encounter misconceptions surrounding the condition13,15. Adequate education and awareness programs targeted at healthcare professionals can enhance recognition and understanding of lipedema’s distinct features, reducing the likelihood of misdiagnosis. Furthermore, public awareness initiatives play a crucial role in diminishing the stigma associated with lipedema, fostering empathy, and promoting a supportive environment for affected individuals169.

Statement 55: “A comprehensive standardized case report form (CRF) should be developed to improve consistency in diagnosis, lipedema reporting, follow-up, and research, and to facilitate, for example, both cohort and longitudinal studies”.
Clarity of statement 100.0%
Level of agreement 96.7%
Inclusion Rating 95.0%
Strength of Evidence 55.9%
Additional Evidence Needed 42.4%
Expert Panel Comment:
Standardized data collection tools are crucial for advancing our understanding of lipedema and fostering collaboration across diverse clinical and research domains. Implementation of a CRF can potentially address existing variations in diagnostic criteria, improve accuracy in reporting, and contribute to the creation of a robust foundation for clinical studies or registries.

Statement 56: “Further research is needed to elucidate the biological mechanisms underlying lipedema, leading to objective diagnostic criteria and targeted therapies”.
Clarity of statement 98.3%
Level of agreement 100.0%
Inclusion Rating 98.3%
Strength of Evidence 57.6%
Additional Evidence Needed 44.8%
Expert Panel Comment:
The call for continued research into the biological mechanisms of lipedema is crucial for advancing our understanding of this complex disease. A comprehensive understanding of these mechanisms is essential for the development of objective diagnostic criteria, robust diagnostic markers and targeted therapeutic interventions. Collaborative efforts between clinicians, researchers, and advocacy groups are integral to driving progress in this field and improving outcomes for individuals affected by lipedema.

Statement 57: “Studies are required to validate diagnostic modalities for lipedema, which assess their reproducibility, sensitivity, and specificity”.
Clarity of statement 100.0%
Level of agreement 100.0%
Inclusion Rating 96.7%
Strength of Evidence 58.6%
Additional Evidence Needed 41.4%
Expert Panel Comment:
While the need for rigorous validation of diagnostic modalities for lipedema is evident, the current landscape lacks comprehensive studies assessing the reproducibility, sensitivity, and specificity of existing diagnostic tools. The urgency for such research is underscored by the diverse clinical presentations and challenges in accurately identifying lipedema, often leading to delayed or incorrect diagnoses. To enhance diagnostic accuracy, future studies should aim to establish standardized protocols for evaluating the reliability and consistency of diagnostic modalities. These protocols should consider the variability in disease manifestations and demographic factors, ensuring applicability across diverse patient populations. Collaborative efforts, such as multicenter trials, could facilitate the accumulation of robust evidence, fostering a more nuanced understanding of diagnostic performance.

Statement 58: “Long-term studies are required to assess the efficacy and safety of treatment modalities for lipedema”.
Clarity of statement 100.0%
Level of agreement 100.0%
Inclusion Rating 98.3%
Strength of Evidence 57.9%
Additional Evidence Needed 46.4%
Expert Panel Comment:
While some studies have provided insights into short-term outcomes, a comprehensive understanding of the long-term effects, durability of response, and potential adverse events is crucial for guiding evidence-based clinical decision-making. The call for long-term studies to assess treatment modalities in lipedema is substantiated by the current gaps in knowledge. Future research endeavors should prioritize extended follow-up periods to inform clinicians, researchers, patients, and service providers about the enduring impact and safety considerations associated with various therapeutic approaches.

Statement 59: “Collaborative efforts between patients, researchers, clinicians and advocacy groups are crucial for advancing knowledge. Translational practice-based application of research knowledge should improve patient care”.
Clarity of statement 100.0%
Level of agreement 98.3%
Inclusion Rating 95.0%
Strength of Evidence 56.9%
Additional Evidence Needed 36.2%
Expert Panel Comment:
Collaborative engagement among patients, researchers, clinicians, and advocacy groups is pivotal for advancing our understanding of complex conditions like lipedema. Such an inclusive approach would foster a more comprehensive perspective, incorporating diverse insights and experiences, which is essential for addressing the multifaceted nature of the disease. Moreover, patient and public involvement in the research process enhances the relevance and applicability of findings to real-world clinical scenarios192–194. The translation of research knowledge into practice is a cornerstone for improving patient care. By bridging the gap between scientific discoveries and clinical applications, we can expedite the integration of evidence-based interventions into routine care, ultimately benefiting individuals affected by lipedema. Emphasizing translational practice ensures that the latest advancements directly influence patient outcomes and treatment strategies, facilitating a more responsive and patient-centered healthcare approach.

Methods
The study was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. Ethics committee approval was not required, as no individual health data were used. Study procedures and reporting followed the DELPHISTAR reporting guidelines for Delphi studies in health research196. A completed DELPHISTAR checklist is provided in the Supplementary Information. No further consulting in regard to the method took place.

Project team selection
This project was led by the Lipedema World Alliance (LWA), a non-profit organization composed of healthcare professionals, researchers, and patient association representatives dedicated to addressing lipedema globally. Experts invited by the LWA Board of Directors to join the Delphi-Consensus Project Team were selected based on their expertise and scholarly contributions in the field. Special attention was given to ensuring a diverse perspective of participants, considering demographic factors (age, sex, country), specialty, and level of experience.

Participant selection
All 103 LWA founding members were invited to participate in the Delphi process via email. Founding Members included (1) physicians/medical doctors, healthcare professionals, and researchers dedicated to lipedema and related pathologies, as well as (2) national and regional organizations registered as not-for-profit and dedicated to fighting lipedema and/or related pathologies, comprising patients and/or family members and/or caregivers and/or professionals. The geographical distribution of the founding members reflects the project’s wide-reaching, transnational, and intercontinental scope.

Modified Delphi process
Delphi statements were developed by the project team around 8 domains regarding lipedema: (1) definition and leading symptoms, (2) pathophysiology, (3) epidemiology, (4) comorbidities and concomitant diseases, (5) impact on quality of life and symptom burden, (6) diagnostic approach, (7) treatment modalities, and (8) future directions.

A three-round Delphi process design was used (Fig. 1). Rounds 1 and 2 were survey-based via an online platform (SurveyMonkey Inc., San Mateo, CA, USA). Round 3 involved an on-site meeting held as part of the Lipedema World Congress on October 7th 2023 in Potsdam, Germany and a final follow-up survey. Although the administrator (PK) was aware of the identities of all respondents for tracking purposes, no identifying information was shared with the Delphi-Consensus Project Team or LWA Board members. For the online voting, all participants remained anonymous to each other throughout the Delphi study. Each stage of the Delphi process was systematically reported to and approved by the LWA Board of Directors.

During each Delphi round, statements were presented to the participant via an online survey. For each statement, participants evaluated 5 criteria: (i) the clarity of the statement, (ii) the degree of agreement with the statement, (iii) the recommendation for inclusion in the final document, (iv) the level of evidence supporting the statement, and (v) whether additional evidence is required to make a conclusive evaluation of the statement. Statement clarity and the need for additional evidence were assessed by yes/no response. Agreement with each statement and recommendation for inclusion were evaluated using a five-point Likert scale, as follows: (1) strongly disagree, (2) disagree, (3) neither agree nor disagree, (4) agree, and (5) strongly agree. Evaluation of the strength of evidence for each statement was similarly conducted using a five-point Likert scale: (1) very low quality, (2) low quality, (3) neither high nor low quality, (4) high quality, and (5) very high quality. The degree of agreement on each criterion was calculated as the percentage of votes with a score of ≥4 on the five-point Likert scale or by the percentage of yes responses.

Consensus, or sufficient agreement, for a given statement was defined a priori as greater than 70% of expert agreement on criterion (ii), along with more than 70% of participants recommending inclusion in the document on criterion (iii)197–200. Criteria (i), (iv), and (v) are not relevant to the consensus threshold but serve to contextualize each statement. Statements that did not meet the established consensus threshold in the subsequent Delphi rounds were excluded from the final document but were included in the supplementary material to reflect the expert’s preferences199,201. In each round of voting, participants were also encouraged to provide comments to explain their respective voting scores, and responses were anonymized. The LWA Delphi-Consensus Project Team reviewed the voting results and comments after each round, refining the statements for subsequent rounds of voting. If the comments implied that language-related misunderstandings contributed to insufficient agreement or that specific phrasing could be modified to achieve a higher level of consensus, the respective statement was adjusted accordingly and re-submitted for voting in the subsequent Delphi round (round 1: #17, #21, #23, #24, #27, #29, #30, #33, #35, #40, #41, #42, #54, #55, #56; round 2: #15, #24, #25, #35, #38).

Delphi evaluation round 1 consisted of 62 statements. All statements were developed by the LWA Delphi-Consensus Project Team and reviewed by the entire LWA board of directors. The online survey evaluation on the statements were distributed between September 9th and September 22nd 2023.

Round 2 included the aggregate results from round 1 and adjusted a total of 29 statements (#5, #7, #10, #13, #14, #15, #19, #20, #21, #24, #25, #26, #28, #32, #33, #34, #35, #36, #37, #39, #41, #43, #44, #47, #50, #51, #52, #57, #59) according to the comments from round 1. Five statements were removed from further evaluation due to an insufficient level of agreement and/or recommendation for inclusion in the final document. Two additional statements (#48, #62) were incorporated based on feedback received, resulting in a total of 59 statements. Online distribution took place between October 1st 2023 and October 6th 2023. Participants were provided with a summary of comments when necessary to understand changes from the previous version.

After the second Delphi evaluation round all LWA founding members were invited to participate in an on-site panel discussion during a dedicated session at the Lipedema World Congress in Potsdam on October 7th 2023. Online participation was also facilitated. During the on-site meeting, results showing the percentage of votes scoring ≥4 on the five-point Likert scale or the percentage of yes responses per statement were shared and related comments were reviewed. Statements that reached consensus in the previous e-Delphi rounds were endorsed with minimal discussion. Statements that did not reach consensus in the previous e-Delphi rounds were discussed, and, when appropriate, reformulated or removed altogether from further evaluation rounds.

Finally, to enhance clarity for the final round (Round 3) of the survey, input from participants of the in-person meeting, along with open-ended feedback from previous Delphi rounds, were both utilized to draft corresponding “expert panel comments” for each of the remaining statements. In addition, 26 statements were revised based on a combination of the discussions held in Potsdam and comments from the online surveys (Statements #2, #3, #4, #6, #10, #16, #18, #19, #24, #31, #33, #36, #39, #40, #41, #42, #44, #46, #47, #49, #51, #52, #53, #54, #55, #57). All remaining 59 statements were included in the final survey after appropriate revision. The online distribution of the survey occurred between April 15th 2024, and July 25th 2024. After the third and final round of the Delphi process, no further modifications were made to the statements, apart from any grammatical changes to implement people-first language. Revisions following careful consideration of all feedback were limited exclusively to the “expert panel comments”.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "The Delphi Consensus-Based Position Paper shows noteworthy consistent results and is a significant review of statements regarding the definition and management of lipoedema, building on the established literature. A comprehensive literature search justified the statements made, and the consensus highlights the need for further research in this condition. The process takes an inclusive approach and focuses on the diversity component. However, the data still lacks gaps to represent the spectrum of protected characteristics in the expert panel (such as gender and age).\nThere were no obvious flaws in the data analysis, but some of the expert panel recommendations may warrant further comment and more specific detail may be needed for the work to be reproduced.\nThe methodology is sound and the work meets the expected standards for a Delphi consensus-based position paper.", "reviewer_2": "Thank you for the opportunity to review this paper. This document is highly needed and represents a comprehensive body of work. This document systematically summarizes important aspects of lipedema and gives insights in where the disagreements in the lipedema research fields are.\nIntroduction\nWell-written introductions, which provides us the framework for understanding the rationale behind this consensus document in lipedema.\nAim\nThe aim of the document is clearly defined.\nMethods\nThe methods section is well-written, and well-explained. A great and thorough job has been done.\nResults\nStatement 2: It is a bit unclear whether the statement means that pain is needed for lipedema diagnosis, or “just” discomfort. Does this mean that pain is now a recognized symptom and necessary for lipedema diagnosis? Or does this mean that discomfort is sufficient?\nStatement 3: Could you please rephrase the argument in statement 3 a bit? It is somewhat unclear why the lack of definitions for anatomical regions is a problem. After references at page 7 lines 277.\nStatement 5: It is somewhat unclear where the threshold for sufficient evidence lies. I understand that it is determined based on expert consensus, but as for the last sentences (lines 311 to 313), I see no reason to include them when the basis is so limited, and as you also stated as well, there is a lack of evidence. I understand that you included these sentences to explain why not everyone agrees, but I would reconsider whether they should be included.\nStatement 7: Same here as the comment above. When it is a consensus document, arguments that are well-documented should be included. The last sentences do not have sufficient evidence, as you also point out. Please reconsider whether they should be included.\nStatement 8 and 10: Feelings of heaviness and easy bruising is also reported by Luta et al. 2025\n(https://pmc.ncbi.nlm.nih.gov/articles/PMC11925301/)\nStatement 15: I would be a bit more cautious about stating that the evidence 'collectively indicates,' given that there are studies showing no increase in ECF in lipedema (Stellmaker et al, 2024). Could it be rephrased a bit more cautiously? Perhaps remove 'collectively'?\nStatement 20: I find the argumentation and discussion here somewhat unclear, and I do not fully understand where the disagreement lies. Could you please rephrase this paragraph?\nStatement 21: I find the sentence about the adipose tissue between lipedema and obesity somewhat unclear (lines 562 to 564). Could you please rephrase it? For example, \"the adipose tissue formed in concomitant lipedema and obesity...\"\nStatement 26: I find this comment largely characterized by speculation without sufficient evidence. Consider reducing it, or alternatively, mention that it is speculative. There is, moreover, a low degree of consensus, weak evidence, and agreement that more evidence is needed. However, still consider whether the sentence with \"rusticanus\" should be included.\nStatement 29: In sentence 2, lines 702-705, you write that progression can be measured by pain and altered body image. I understand that body image can be affected by unsuccessful therapeutic interventions and ideas, but I suggest rephrasing this sentence. As it stands, I interpreted it as the progression of lipedema being measured by increased pain and altered body image. I would rather change it to an increase in leg volume, for example.\nStatement 32: You may also consider including the study by Dinnendahl et al here as well, reference number 30.\nStatement 33: I find it a bit difficult to understand where the disagreement lies. I see that the consensus is at 82%, but there is nothing in the comments that indicates anyone disagrees with this.\nStatement 36: I find it a bit unclear what is meant in this sentence about the various factors contributing to differences in symptom progression. How would genetic predisposition affect differences in symptom progression?\nStatement 37: Consider rephasing limb volume excess to excess limb volume. Also, please rephrase the second sentence (lines 850-842). It seems a bit unclear where the disagreements are. Does this mean that some authors believe that lipedema can lead to obesity?\nStatement 42: I find the meaning of the third sentence a bit unclear and suggest rephrasing it. What is meant by 'excessive strain,' and wouldn't walking be a weight-bearing activity that could lead to stress on muscles and joints? Could you also clarify muscle tone a bit? Additionally, I suggest choosing another reference that is available in English to make it easier for readers\nStatement 45: Suggests adding this paper (https://pubmed.ncbi.nlm.nih.gov/40125475/) after effect of inflammation following ketogenic diets in lipedema. You can also consider adding “pain relief” in addition to symptom relief.\nStatement 47: Please rephrase sentence number two (line 2035), as this sentence seem unclear. e.g. Obesity is usually classified using BMI (>30 kg/m2).\nStatement 49: I suggest using an English-language reference instead of a German one, as it may make it easier for readers. I am also not sure that walking is associated with increased muscle strength, so I suggest rephrasing this sentence (line 1071-1073).\nStatement 51: I find it a bit unclear how lipedema leads to the worsening of obesity symptoms, as referred to in your mention of 'vice versa.' What is classified as obesity symptoms, is it increased fat tissue or inflammation?\nDiscussion\nI would like to emphasize the importance of detailing the distribution of patient representatives. Additionally, in lines 1287- 1289 on page 29, you mention that the populations affected by lipedema remain underrepresented in this work. However, the table showing the distribution of patient representatives indicates a high percentage of the population. Could you clarify what is meant by this statement in the discussion? Are you referring to geographical distribution? Please also specify which populations, based on geography, are not included in the document.\nCould you please clarify why there are so many more participants in round three compared to the earlier rounds?\nConclusion:\nWe understand that it is not possible to draw conclusions based on so many guidelines, but the conclusion feels more like a summary. If this is not determined by the journal, perhaps the heading could be changed to 'Summary'?\nAcknowledgement\nWe see coauthors listed as “participated in the voting process, but not in the interpretation of the results”. However, further down, it says that all coauthors were included in editing and commenting on the manuscript at all stages. We found it a bit unclear who participated in which parts. Could this be clarified?\nMinor\nPage 6, line 261: please remove the extra space between the references, should be phrased as (25-30)\nPage 7, line 277: please remove the extra space between the references, should be phrased (31-37).\nPage 7, line 296: typo, reports instead of report\nThanks for the opportunity to review this article.", "reviewer_3": "I have had the opportunity to review this Delphi study from a methodological point of view. The authors provide a well- reasoned rationale for the study design and have conducted the Delphi study with rigor and transparency. I offer the following suggestions to further improve the clarity of the methods.\nSpecific comments\n1. The abstract uses the terms \"90% to 100% consensus\" and \"80% to 90% consensus\". I suggest replacing \"consensus\" with \"agreement\".\n2. Line 176: \"Round 2 included the aggregated results from Round 1\". Please clarify what type of feedback was provided to participants (e.g. frequencies, means, summary of comments).\nSimilarly, in line 193: \"along with feedback from previous Delphi rounds\" - it would be helpful to specify the type of this feedback.\n3. Line 179f: \"Five statements were removed from further evaluation due to an insufficient level of agreement.\" Please define what constitutes \"insufficient level of agreement\" and specify the threshold used.\n4. You indicate that consensus was defined on the basis of criteria ii and iii. Please clarify the role of criteria i, iv and v. A brief explanation would enhance methodological transparency.\nGeneral comments\n• I recommend using and referring to a Delphi reporting guideline, e.g. DELPHISTAR (via the EQUATOR network), to further enhance methodological transparency and comparability with other Delphi studies.\n• Although my review focused on the methodology, the discussion could benefit from a clearer link to the existing literature to better contextualize the findings.", "reviewer_4": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts."}, "author_response": "Reviewer #1 (Remarks to the Author):\nThe Delphi Consensus-Based Position Paper shows noteworthy consistent results and is a\nsignificant review of statements regarding the definition and management of lipoedema,\nbuilding on the established literature. A comprehensive literature search justified the\nstatements made, and the consensus highlights the need for further research in this\ncondition. The process takes an inclusive approach and focuses on the diversity\ncomponent. However, the data still lacks gaps to represent the spectrum of protected\ncharacteristics in the expert panel (such as gender and age).\nThank you for the supportive assessment of the manuscript's key elements.\nInstead of the participants' ages, the authors provided their years of experience in\ntreating lipedema, as this is more relevant to the topic (Table 3). Gender\ninformation has been added in Section 3 (Results).\nLine 224: “In the final Delphi evaluation round 3, 71 out of 103 founding members\nof the LWA participated (34 female, 37 male), representing 19 countries across 5\ncontinents (Table 2).”\nThere were no obvious flaws in the data analysis, but some of the expert panel\nrecommendations may warrant further comment and more specific detail may be needed\nfor the work to be reproduced.\nWe thank the reviewer for the helpful input to improve the manuscript and refine\nspecific wording. The expert panel comments were intentionally kept brief to\nsupport understanding, prevent misunderstandings, and provide context in cases of\ndissent. They are not intended as a comprehensive literature review, which would\nexceed the manuscript’s scope. Nonetheless, we carefully reviewed all statements\nand revised the comments where appropriate. Please find additional information in\nresponses to the comments from Reviewer 2.\nThe methodology is sound and the work meets the expected standards for a Delphi\nconsensus-based position paper.\nOnce again, thank you for your positive evaluation of our methodology.\nReviewer #2 (Remarks to the Author):\nThank you for the opportunity to review this paper. This document is highly needed and\nrepresents a comprehensive body of work. This document systematically summarizes\nimportant aspects of lipedema and gives insights in where the disagreements in the\nlipedema research fields are.\nMany thanks to Siren Nymo and Julianne Lundanes for recognizing the\nmanuscript’s importance and for their thorough, detailed analysis, which will\nsignificantly strengthen it.\nIntroduction\nWell-written introductions, which provides us the framework for understanding the\nrationale behind this consensus document in lipedema.\nThank you.\nAim\nThe aim of the document is clearly defined.\nAgreed.\nMethods\nThe methods section is well-written, and well-explained. A great and thorough job has\nbeen done.\nThank you for your kind assessment.\nResults\nStatement 2: It is a bit unclear whether the statement means that pain is needed for\nlipedema diagnosis, or “just” discomfort. Does this mean that pain is now a recognized\nsymptom and necessary for lipedema diagnosis? Or does this mean that discomfort is\nsufficient?\nThe formulation of this statement required extensive deliberation by the authors\nand expert panel, due to the wide international variation in how this symptom is\ndescribed. The second part of the expert panel comments serves to clarify the\nselected phrasing, noting: „The presence of pain varies widely among individuals,\nranging from mild discomfort to severe, chronic pain.“ Statement 6 provides\nadditional detail on pain in lipedema and emphasizes the pressing need for a\nstandardized definition.\nStatement 3: Could you please rephrase the argument in statement 3 a bit? It is\nsomewhat unclear why the lack of definitions for anatomical regions is a problem. After\nreferences at page 7 lines 277.\nThe distinction between torso and extremities shapes the debate on which regions\nare affected by lipedema, given that the torso is generally seen as unaffected. It also\nmay assist in treatment planning of affected regions to best understand their\nanatomical extent. For example, the pelvic girdle, though positioned in the lower\ntorso, is commonly classified as part of the extremities based on embryological,\nfunctional and evolutionary considerations. We agree that the challenge stems from\ninconsistent terminology rather than a lack of clear definitions. The section has been\nadjusted to reflect this.\nLine 289: “However, inconsistent terminology for anatomical regions in the\nliterature necessitates clarification in order to more clearly discuss the regions\naffected by lipedema.”\nStatement 5: It is somewhat unclear where the threshold for sufficient evidence lies. I\nunderstand that it is determined based on expert consensus, but as for the last\nsentences (lines 311 to 313), I see no reason to include them when the basis is so\nlimited, and as you also stated as well, there is a lack of evidence. I understand that you\nincluded these sentences to explain why not everyone agrees, but I would reconsider\nwhether they should be included.\nWe appreciate the ability to recognize and address internal discussions within the\nexpert panel and author team during the review process. Ultimately, the authors\nagreed that the expert panel comment should transparently address the dissent\nconcerning the exclusion of hands and feet in lipedema SAT accumulation. The\nstatement about absence of definitive evidence potentially serves as a call for\nresearch about this aspect of lipedema, and case examples are important to note as\ninitial evidence. The etiology is left open, linking it to disease progression or in\nrelation to possible comorbidities. Overall, this clarification is considered important\nto explain why near-unanimous agreement on such a clear statement was not\nachieved. Therefore, we respectfully wish to keep the present discussion rephrasing\nto:\nLine 324: “However, although not constituting definitive evidence, patient reports\nsuggest […]”\nStatement 7: Same here as the comment above. When it is a consensus document,\narguments that are well-documented should be included. The last sentences do not have\nsufficient evidence, as you also point out. Please reconsider whether they should be\nincluded.\nThe authors aim to clarify that symptoms outside the extremities, excluding hands\nand feet, are likely related to comorbidities. Without this specification, the\napproximately 85% agreement rate might be difficult to interpret. We have\nrephrased the statement about evidence to:\nLine 358: “However, although not constituting definitive evidence, patient reports\nsuggest […]”\nStatement 8 and 10: Feelings of heaviness and easy bruising is also reported by Luta et\nal. 2025 (https://pmc.ncbi.nlm.nih.gov/articles/PMC11925301/)\nThank you for recommending this reference. It has now been incorporated, as it\nwas not accessible when the manuscript was first submitted.\nStatement 15: I would be a bit more cautious about stating that the evidence 'collectively\nindicates,' given that there are studies showing no increase in ECF in lipedema\n(Stellmaker et al, 2024). Could it be rephrased a bit more cautiously? Perhaps remove\n'collectively'?\nWe acknowledge that the original phrasing may have been overly definitive and\nhave removed \"collectively\" as recommended. Additionally, the report by\nStellmaker et al was not available during the Delphi process, and we will therefore\nnot include it, given its potential to impact the statement. Notably, the study\nexcluded participants with lymphatic insufficiency on ICG-lymphography, which\nmay explain the absence of ECF in their cohort.\nStatement 20: I find the argumentation and discussion here somewhat unclear, and I do\nnot fully understand where the disagreement lies. Could you please rephrase this\nparagraph?\nThe differing assessments were made to highlight that BMI is an inadequate\nmeasure for differentiating lipedema from obesity. This aspect was further\nemphasized in the panel comment:\nLine 555: “[…] However, BMI is not an ideal tool to assess obesity in patients with\nlipedema due to the disproportionate body habitus inherent in lipedema [99],\npotentially contributing to divergent clinical evaluations and interpretations of\nexisting literature. Nevertheless, when both conditions coexist, appropriate\ntreatment must be provided for each as a separate disease. […]”\nStatement 21: I find the sentence about the adipose tissue between lipedema and\nobesity somewhat unclear (lines 562 to 564). Could you please rephrase it? For example,\n\"the adipose tissue formed in concomitant lipedema and obesity...\"\nThe section was rephrased to improve clarity.\nLine 577: “Lipedema adipose tissue exhibits distinct morphological, molecular and\nmetabolic characteristics compared to obesity-type adipose tissue [38, 104].”\nStatement 26: I find this comment largely characterized by speculation without sufficient\nevidence. Consider reducing it, or alternatively, mention that it is speculative. There is,\nmoreover, a low degree of consensus, weak evidence, and agreement that more\nevidence is needed. However, still consider whether the sentence with \"rusticanus\"\nshould be included.\nThe Reviewer’s assessment of this statement as speculative is reflected in the\nlower agreement among the panel for this statement. The current supporting\nevidence and clinical observations are important to keep because this represents\nthat basis of the statement. Recognizing the speculative nature of the connection\nbetween lipedema and HSD, the authors have revised the expert panel comments\nfor clarity. The mention of the sub-type “rusticanus Moncorps type” remains, as it\npresents a potentially testable hypothesis.\nLine 661: “Evidence suggests that women with lipedema exhibit decreased elasticity\nin both skin [119] and aorta [120], along with joint hypermobility [22, 121, 122] and\nmuscle weakness [123]. There is speculation about a link between lipedema and\nconnective tissue disorders, specifically hypermobility spectrum disorders (HSD),\nalthough no conclusive underlying mechanism has been identified [124]. Considering\nthe inconsistency of HSD in lipedema, a hypothesis has proposed categorizing it as a\nsubtype (“rusticanus Moncorps type”) of lipedema [119]. Further investigation is\nneeded to confirm a definitive association between lipedema and HSD.”\nStatement 29: In sentence 2, lines 702-705, you write that progression can be measured\nby pain and altered body image. I understand that body image can be affected by\nunsuccessful therapeutic interventions and ideas, but I suggest rephrasing this sentence.\nAs it stands, I interpreted it as the progression of lipedema being measured by increased\npain and altered body image. I would rather change it to an increase in leg volume,\nfor example.\nThank you for highlighting the potential for misunderstanding. The phrase “altered\nbody image” has been revised to “disproportionate adipose tissue accumulation” to\nmore precisely describe the clinical progression.\nStatement 32: You may also consider including the study by Dinnendahl et al here as\nwell, reference number 30.\nThis reference should clearly be included here, as the method holds great\npotential to address the earlier-discussed ambiguity in categorizing the symptom\n\"pain.\" The source has been added. Thank you for this suggestion.\nStatement 33: I find it a bit difficult to understand where the disagreement lies. I see\nthat the consensus is at 82%, but there is nothing in the comments that indicates anyone\ndisagrees with this.\nThe main point of disagreement was that some experts wished to eliminate BMI as\nan anthropometric measure for patients with lipedema. A statement was included to\nreflect this divergence and to emphasize the authors' view that BMI remains an\nimportant standard measure.\nLine 791: „Despite its limited significance in lipedema, BMI can support disease\nmonitoring due to its simplicity in measurement and interpretation.”\nStatement 36: I find it a bit unclear what is meant in this sentence about the various\nfactors contributing to differences in symptom progression. How would genetic\npredisposition affect differences in symptom progression?\nThe central point of this statement is that disease progression (e.g., by clinical\nstages) does not inevitably occur, unlike in lymphedema. Although progression is\nfrequently seen, its pattern is quite heterogeneous. This is adequately clarified in\nthe first section of the expert panel commentary. The second part refers to factors\npotentially involved, including hormonal changes, weight gain, and lifestyle\ninfluences, which are undisputed contributors. We agree that \"genetic\npredisposition\" may not have been the most precise term and have revised it to\n\"individual predisposition.\" We also agree that robust evidence exists mainly for\nweight gain, as noted in the concluding sentence.\nStatement 37: Consider rephasing limb volume excess to excess limb volume. Also,\nplease rephrase the second sentence (lines 850-842). It seems a bit unclear where the\ndisagreements are. Does this mean that some authors believe that lipedema can lead to\nobesity?\nThe divergence of opinion relates to patients affected by both lipedema and\nobesity. It was clarified that, in such cases, a clear distinction cannot yet be made,\nand both conditions may contribute to excess limb volume.\nLine 862: “Given the high number of patients with lipedema who also suffer from\nconcomitant obesity, excess limb volume can be attributed to both underlying\nconditions.”\nStatement 42: I find the meaning of the third sentence a bit unclear and suggest\nrephrasing it. What is meant by 'excessive strain,' and wouldn't walking be a weight-\nbearing activity that could lead to stress on muscles and joints? Could you also clarify\nmuscle tone a bit? Additionally, I suggest choosing another reference that is available in\nEnglish to make it easier for readers\nWe recognize that the original phrasing did not adequately reflect the evidence\nlevel and have adjusted the section. \"Aquatic exercise\" now replaces \"swimming or\nwalking,\" and \"muscle strength\" replaces \"muscle tone.\" Relevant English-language\nreferences have been added.\nLine 958: “Tailored exercise regimes, such as aquatic exercise, are often\nrecommended to promote lymphatic flow [150] and muscle strength without\nplacing excessive strain on affected limbs [149, 151].”\nStatement 45: Suggests adding this paper\n(https://pubmed.ncbi.nlm.nih.gov/40125475/) after effect of inflammation following\nketogenic diets in lipedema. You can also consider adding “pain relief” in addition to\nsymptom relief.\nThe reference has been included. In light of the unclear definition of lipedema pain\nand the variability in symptom presentation, the authors prefer to refer generally to\n'symptom relief' from ketogenic diets rather than specifically mentioning 'pain'.\nStatement 47: Please rephrase sentence number two (line 2035), as this sentence seem\nunclear. e.g. Obesity is usually classified using BMI (>30 kg/m2).\nThe sentence was rephrased to improve clarity.\nLine 1055: “Obesity classification typically relies on BMI. However, in the context\nof lipedema and in line with statement 33, utilizing alternative anthropometric\nmeasures—such as WHtR—may be more appropriate for assessing or excluding\noverweight and obesity, particularly in the context of metabolic health\ncategorization [100].”\nStatement 49: I suggest using an English-language reference instead of a German one,\nas it may make it easier for readers. I am also not sure that walking is associated with\nincreased muscle strength, so I suggest rephrasing this sentence (line 1071-1073).\nEnglish-language references were added where necessary and appropriate. The\nsentence, which links yoga and walking to increased muscle strength, was revised\nto present them as examples of \"structured exercise.\" Additionally, a reference was\nincluded that the authors believe sufficiently supports the association between long-\nterm walking exercise and increased muscle strength.\nLine 1092: “Moreover, structured exercise—such as walking and yoga—have been\nassociated with improved muscular strength, and psychological well-being, factors\nthat are particularly relevant for individuals with lipedema [123, 178, 179].”\nStatement 51: I find it a bit unclear how lipedema leads to the worsening of obesity\nsymptoms, as referred to in your mention of 'vice versa.' What is classified as obesity\nsymptoms, is it increased fat tissue or inflammation?\nThe sentence was revised to clarify causality. Lipedema-related symptoms can\nsignificantly impair general mobility—e.g., due to excess tissue causing mechanical\nirritation and movement-related pain—suggesting that reduced physical activity\nmay contribute to the progression of coexisting obesity. Furthermore, patients with\nboth lipedema and obesity tend to experience significantly diminished quality of life,\nwhich may reduce motivation for physical activity and the adoption of a healthy\nlifestyle. Additional references have been added.\nIt should also be noted that the authors refer to a worsening of “obesity” in\ngeneral, not specifically to “obesity symptoms,” thereby including comorbidities\nsuch as type 2 diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver\ndisease, and polycystic ovary syndrome.\nLine 1120: “Existing literature highlights the bidirectional interplay between\nobesity and lipedema, with obesity potentially exacerbating lipedema symptoms\n[183] and vice versa due to impaired mobility, pain or psychological burden linked\nto lipedema [19, 46, 175, 177, 184].”\nDiscussion\nI would like to emphasize the importance of detailing the distribution of patient\nrepresentatives.\nA section was added at the beginning of the results to address the geographic\ndistribution of patient advocates in the third Delphi round.\nLine 230: “Seven countries in total were represented by the patient advocates,\nwith ten of the twelve originating from Europe.”\nAdditionally, in lines 1287-1289 on page 29, you mention that the populations affected\nby lipedema remain underrepresented in this work. However, the table showing the\ndistribution of patient representatives indicates a high percentage of the population.\nCould you clarify what is meant by this statement in the discussion? Are you referring to\ngeographical distribution? Please also specify which populations, based on geography, are\nnot included in the document.\nAs correctly assumed, this clause refers to the geographic distribution of\nparticipants in the Delphi process. There are no participants from Africa, only one\nfrom India in Asia, two from Brazil in South America, and two from Australia. Given\nthe predominance of participants from Europe and the United States, several\nsignificant populations are notably underrepresented.\nLine 1309: “Additionally, although experts from 19 countries participated,\nsignificant populations affected by lipedema—such as those in Asia and Africa—\nremain underrepresented in this work.”\nCould you please clarify why there are so many more participants in round three\ncompared to the earlier rounds?\nThis section was included following the relevant remark in the study limitations to\nprovide clarification:\nLine 1373: “The in-person meeting after Round 2 during the dedicated session at\nthe Lipedema World Congress in Potsdam on October 7, 2023, significantly\nincreased the project's visibility and attention. This led to a higher number of\nparticipants in the third Delphi round, ensuring the final results are well-founded\nand reliable.”\nConclusion:\nWe understand that it is not possible to draw conclusions based on so many guidelines,\nbut the conclusion feels more like a summary. If this is not determined by the journal,\nperhaps the heading could be changed to 'Summary'?\nThe authors have no preference and respectfully defer to the Editorial Board to\ndecide whether “Summary” would be more appropriate.\nAcknowledgement\nWe see coauthors listed as “participated in the voting process, but not in the\ninterpretation of the results”. However, further down, it says that all coauthors were\nincluded in editing and commenting on the manuscript at all stages. We found it a bit\nunclear who participated in which parts. Could this be clarified?\nIt was clarified that all listed authors also participated in the Delphi process,\nwhereas those mentioned in the acknowledgments voted but did not participate in\ninterpreting the findings. Additionally, the authors’ names have been removed from\nthe acknowledgments in the Delphi voting process.\nLine 2003:” In addition to the author team, the below specialists participated in\nthe voting process of the Delphi methodology, but not in interpretation of the\nresults, and agreed to be mentioned here.”\nMinor\nPage 6, line 261: please remove the extra space between the references, should be\nphrased as (25-30)\nThe space has been removed.\nPage 7, line 277: please remove the extra space between the references, should be\nphrased (31-37).\nThe space has been removed.\nPage 7, line 296: typo, reports instead of report\nThe typo has been corrected.\nThanks for the opportunity to review this article.\nReviewer #3 (Remarks to the Author):\nI have had the opportunity to review this Delphi study from a methodological point of\nview. The authors provide a well-reasoned rationale for the study design and have\nconducted the Delphi study with rigor and transparency. I offer the following suggestions\nto further improve the clarity of the methods.\nThank you for recognizing our commitment to working accurately and\ntransparently.\nSpecific comments\n1. The abstract uses the terms \"90% to 100% consensus\" and \"80% to 90% consensus\".\nI suggest replacing \"consensus\" with \"agreement\".\nThe comment was well received, and the wording was adjusted accordingly. The\nabstract now states:\nLine 68: “Thirty-six statements reached 90% to 100% agreement, 17 statements\nreached 80% to 90% agreement, and 6 statements reached 70% agreement.”\n2. Line 176: \"Round 2 included the aggregated results from Round 1\". Please clarify what\ntype of feedback was provided to participants (e.g. frequencies, means, summary of\ncomments).\nDuring this phase of the Delphi voting, participants were provided with a summary\nof comments when necessary to understand changes from the previous version.\nApproval rates were not provided.\nLine 190: “Participants were provided with a summary of comments when\nnecessary to understand changes from the previous version.”\nAfter the second survey round, relevant comments were discussed at the on-site\nmeeting, and the percentage of votes scoring ≥4 on the five-point Likert scale or\nthe percentage of yes responses for each statement was disclosed. Additionally, in\nthe third online Delphi round, participants were shown the expert panel comment\nformulated based on the feedback.\nLine 195: “During the on-site meeting, results showing the percentage of votes\nscoring ≥4 on the five-point Likert scale or the percentage of yes responses per\nstatement were shared and related comments were reviewed.”\nSimilarly, in line 193: \"along with feedback from previous Delphi rounds\" - it would be\nhelpful to specify the type of this feedback.\nThis refers to related open comments on statements with limited agreement rates\nthat required clarification.\nLine 203: “[…] along with open-ended feedback from previous Delphi rounds […]”\n3. Line 179f: \"Five statements were removed from further evaluation due to an\ninsufficient level of agreement.\" Please define what constitutes \"insufficient level of\nagreement\" and specify the threshold used.\nConsensus was previously defined as greater than 70% expert agreement on a\ncriterion, accompanied by more than 70% of participants recommending its\ninclusion in the document. In this context, this is equivalent to “sufficient\nagreement.” This clarification has been added.\nLine 161: “Consensus, or sufficient agreement, for a given statement was defined\na priori as greater than 70% of expert agreement on criterion (ii), along with more\nthan 70% of participants recommending inclusion in the document on criterion (iii)\n[12-15].”\n4. You indicate that consensus was defined on the basis of criteria ii and iii. Please clarify\nthe role of criteria i, iv and v. A brief explanation would enhance methodological\ntransparency.\nA section addressing the relevance of Criteria (i), (iv), and (v) has been added.\nLine 164: “Criteria (i), (iv), and (v) are not relevant to the consensus threshold\nbut serve to contextualize each statement.”\nGeneral comments\n• I recommend using and referring to a Delphi reporting guideline, e.g. DELPHISTAR (via\nthe EQUATOR network), to further enhance methodological transparency and\ncomparability with other Delphi studies.\nThe DELPHISTAR reporting guidelines were applied, with the filled checklist\nprovided in the supplementary files.\nLine 128: “The study was conducted and reported following the DELPHISTAR\nreporting guidelines for Delphi studies in health research [12]. A completed\nDELPHISTAR checklist is provided in supplemental file xxx.”\n• Although my review focused on the methodology, the discussion could benefit from a\nclearer link to the existing literature to better contextualize the findings.\nThe authors respectfully disagree with the reviewer on this point. The manuscript\nis intentionally structured so that each statement is accompanied not only by an\nobjective evaluation but also by an “expert panel comment” placing it in the context\nof existing literature. Providing a full contextualization of all findings would exceed\nthe scope of the discussion, which is why a different structure was chosen from the\noutset. With due respect to the reviewer’s comment, the authors prefer to maintain\nthe current manuscript format.\nReviewer #4 (Remarks to the Author):\nI co-reviewed this manuscript with one of the reviewers who provided the listed reports.\nThis is part of the Nature Communications initiative to facilitate training in peer review\nand to provide appropriate recognition for Early Career Researchers who co-review\nmanuscripts.\nWe sincerely appreciate your involvement as an Early Career Researcher, and the\nthorough review you provided of our manuscript. The valuable feedback has clearly\nenhanced its quality."}, {"round": 2, "reviewer_comments": {"reviewer_1": "The authors have incorporated most of the reviewers' feedback, and where they haven't, they provide clear reasons for disagreement. Certain statements have been reworded to allow for the reader's interpretation and highlight the varied opinions of the project team of experts.", "reviewer_3": "I would like to thank the authors for their thoughtful and thorough revisions and detailed responses to the reviewers’ comments. The manuscript is now clearer and more transparent. The authors have carefully addressed the comments. As all concerns have been addressed to my satisfaction, I support the publication of the manuscript in its current form.", "reviewer_4": "I co-reviewed this manuscript with one of the reviewers who provided the listed reports. This is part of the Nature Communications initiative to facilitate training in peer review and to provide appropriate recognition for Early Career Researchers who co-review manuscripts."}, "author_response": ""}]

Decision letter