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DOI: 10.1055/a-2530-5875
Lipedema: Clinical Features, Diagnosis, and Management
- Abstract
- Introduction
- Methods and Materials
- Narrative Review
- Conclusion
- References
Abstract
Lipedema is an adipose tissue disorder that principally affects women and is frequently misidentified as obesity or lymphedema. There have been relatively few studies that have precisely defined the pathogenesis, epidemiology, and treatment approaches for lipedema. However, successfully recognizing lipedema as a distinct condition is important for proper management. This review aimed to examine the existing literature on the epidemiology, pathogenesis, clinical presentation, differential diagnosis, and treatments for lipedema. The current research indicates that lipedema appears to be a clinical entity related to genetic factors and fat distribution, although distinct from lymphedema and obesity. Some available treatments include complex decongestive physiotherapy, liposuction, and laser-assisted lipolysis. The management of lipedema is complex and differs from that of lymphedema. Further high-quality randomized controlled trials are urgently needed to continue advancing our understanding of this often neglected disease and exploring optimal medical and surgical treatment regimens tailored specifically for lipedema patients. In summary, despite frequent misdiagnosis, enhanced recognition, and research into customized therapeutic strategies for this poorly characterized but likely underdiagnosed disorder represent promising steps forward.
Level of evidence N/A.
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Introduction
Lipedema is a condition affecting adipose tissues that was first identified by Wold et al.[1] The disease is characterized by its progressive nature, attributed to the abnormal accumulation of subcutaneous fat. This leads to developing bilateral lower limb and/or upper extremity enlargement and swelling. Moreover, lipedema typically spares the hands, feet, and trunk; however, the arms are frequently affected.[2] [3] [4] It is crucial to note that the actual cause of the disease is yet unknown.[5]
Primarily, females between puberty and the third decade of life, are more susceptible to and predominantly affected by this condition than males.[1] [6] Moreover, stressful life events, trauma, or surgical procedures can trigger the onset of lipedema.[4] Notably, there is a belief in the potential inheritance of lipedema, which may occur through either autosomal dominant or X-linked patterns with sex limitation. Although the specific genes and proteins associated with lipedema are not fully understood and detectable biomarkers in lipedema patients remain limited, genetic inheritance has been observed in approximately 60% of cases, with suggestions of the involvement of multiple genes.[3] [7] [8] Furthermore, lipedema can contribute to various health complications, including hypothyroidism, electrolyte imbalance due to the disposition of sodium within the skin, cardiovascular problems, and reduced levels of vitamin D, particularly in cases where the body mass index (BMI) surpasses average values. Additionally, psychological distress may ensue, leading to a compromised quality of life among affected individuals.[9] [10] [11] [12] [13] [14] [15] [16] [17]
Lipedema is a clinical diagnosis requiring extensive knowledge and identification of the condition, proper history taking, and physical examination.[18] However, it is possible to misdiagnose it due to the circumferential enlargement of the legs, which is comparable to lymphedema and nonlipedema obesity. Apart from this, lipedema can be distinguished after multiple attempts of weight reduction that have shown to have modest effects on the lower extremities.[8] [19] [20] [21] Long-term lipedema may result in secondary lymphedema due to mechanical pressure on the lymphatic system due to fatty hypertrophy. Additionally, elevated sodium levels may lead to the recruitment of inflammatory mediators that directly impede lymphatic evacuation, exacerbating edema production, especially in the latter stages where lymphedema frequently coexists with lipedema.[22] [23] [24] [25] [26] As a result, diagnosis might be delayed for up to 10 years.[27]
Hence, there is an urgent need to comprehensively review the existing literature on lipedema to delineate its distinct epidemiology, pathogenesis, diagnostic features, and tailored therapeutic approaches. This review aims to provide clearer insight into this perplexing condition and inform future research directions by evaluating the current knowledge gap and limitations of prior studies. The goal is to promote early, accurate diagnosis and appropriate multimodal care of lipedema patients through evidence-based recommendations. Enhanced understanding of this distinct disorder is imperative to develop more effective therapies and improve prognosis and life quality for those affected.
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Methods and Materials
Articles for this narrative review, conducted in January 2024, were gathered from the Google Scholar and PubMed databases. The search terms “Lipedema,” “Lipoedema,” “Lipoedemas,” and “Lipolymphedema” were employed. After thorough screening and searching, thirty publications were selected to address the research objectives.[15] [20] [26] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] The inclusion criteria for this narrative review are as follows: studies focusing on lipedema in human subjects were selected. Both research articles and reviews published in peer-reviewed journals were included to ensure the credibility and reliability of the sources. The studies needed to provide clinical insights into lipedema's characteristics, diagnosis, or management. Only publications available in English were considered to ensure accessibility for review and analysis. The review encompassed studies across different age groups, including both pediatric and adult populations. Additionally, research exploring diverse management strategies for lipedema was included to provide a comprehensive understanding of the condition. The assessment involved reviewing relevant article titles and abstracts, with subsequent retrieval of full text.
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Narrative Review
Epidemiology and Prevalence of Lipedema
Worldwide, very few papers report the prevalence of lipedema, as it is a frequently misdiagnosed or underdiagnosed disease. It is estimated that the prevalence of lipedema is around 11%, ranging between 15 and 18% in the United States and across Europe, respectively.[18] [29] [33] [34] These prevalence estimates are likely underestimates due to the high frequency of misdiagnosis and underdiagnosis of lipedema.
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Demographic Characteristics
Although primarily known as an exclusively female disease, lipedema has rarely been reported in men. Onset often occurs during puberty, the third decade of life, or after events like menopause and childbirth, suggesting a link to hormonal fluctuations like estrogen.[3] [15] Lipedema is associated with high BMI for both overweight and obesity.[15] Despite normal upper body habitus, lipedema patients exhibit disproportion between the arms and legs, with a waist-to-hip ratio <1.[3] [6] Lipedema showed potential inheritance, from 16 to 64% of patients report a family history of lipedema.[15] [55] A study in Brazil correlated anxiety, depression, hypertension, and anemia with increased lipedema risk in women.[46]
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Pathophysiology
To date, no pathophysiological mechanism has been identified; however, several theories have been proposed, mainly revolving around the hormonal influence of estrogen, abnormal adipogenesis, and pathological angiogenesis. Estrogen plays a significant role in the body, especially in females.[31] One is controlling genes that lead to endothelial barrier disruption, as Szel et al stated. Additionally, it is involved in the sympathetic innervation of fatty tissue, explaining the neuropathy associated with lipedema.[2] [29] Lipedema is characterized by its increased palpation sensitivity, attributed to adipocyte necrosis and macrophages secondary to hypoxia from increased fat deposition.[29] [33] [56] [57] Another theory suggests abnormal angiogenesis and loss of elasticity. Although lymphatic vessels and capillaries typically lack elastic tissue, the surrounding connective tissue possesses elasticity.[33] Therefore, in such cases, lymphatic vessels lose their ability to open properly under increased pressure within the extracellular matrix, resulting in leakage from the capillaries.[15] [58] Moreover, Siems et al propose that hypoxic adipose tissue induces the proliferation of blood vessels by overly stimulating vascular endothelial growth factors.[15] [59]
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Genetic Factors
Lipedema is inherited via X-linked dominant or autosomal dominant patterns with a gender bias toward females. This condition can be divided into two main types: syndromic and nonsyndromic.[31] In syndromic lipedema, notable genetic mutations include: the PIT-1 mutation, affecting anterior pituitary gland hormone secretion—specifically growth hormone, prolactin, and thyroid-stimulating hormone—leading to potential hormone deficiencies and lipedema.[31] [33] [60] [61] [62] Another genetic condition, Sotos Syndrome, features mutations or microdeletions in the NSD1 gene and is characterized by early excessive growth, macrocephaly, and developmental delays, with some diagnosed cases also presenting lipedema.[31] [60] [63] Lastly, Williams Syndrome, caused by a microdeletion in chromosome 7 that results in elastin gene loss, has been observed with a unique lipedema phenotype, including reduced bone mass and a predominance in males without pain or tenderness sensitivity.[31] [33] [64]
For nonsyndromic lipedema, mutations in the aldo-keto reductase gene have been implicated. This gene plays a crucial role in converting active progesterone into its inactive form. A mutation here can disrupt this process, resulting in progesterone accumulation that may contribute to abnormal fat deposition, a hallmark of lipedema, and associated weight gain.[31] [65]
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Clinical Manifestation and Diagnosis
Lipedema primarily presents as an enlargement of the lower limbs, and may also symmetrically affect the upper limbs. It is characterized by clear demarcations at the feet and hands, leading to the distinctive “cuff sign.” The distribution of fat is disproportionately concentrated on the outer regions of the buttocks, thighs, and calves while sparing the abdomen, feet, and hands. The condition is classified into five types based on the pattern of fat distribution, as detailed in [Table 1] and depicted in [Fig. 1].[15] Among these types, the most commonly observed are types 1 to 3, compared with types 4 and 5 ([Fig. 1]). As for the severity, Herbes et al have classified lipedema into stage 1, involving an enlarged hypodermis with smooth and intact skin; stage 2, characterized by the nodular changes in adipose tissue with irregular skin surface; stage 3, characterized by contour deformity of the knees and thighs as a result of the considerable growth of nodular fat, and stage 4 involving the coexistence of lymphedema ([Fig. 2]).[31] [34] [66] [67] [68] [69] [70] In their comprehensive guidelines for the diagnosis of lipedema, Halk and Damstra present a detailed framework, as outlined in [Table 2], which enumerates critical diagnostic criteria and considerations for clinicians and researchers.[66] Key features distinguishing lipedema from lymphedema and obesity include susceptibility to bruising, pain upon palpation, and progressive enlargement that does not respond to lifestyle changes. The pain associated with lipedema is often described as a pressure-like, dull, and heavy sensation, primarily affecting the anterior tibial and femoral regions. This discomfort may be provoked by light touch and exacerbated by prolonged standing or sitting, becoming particularly noticeable toward the day's end.[30] [40] [54] Joint hypermobility is another characteristic, with studies indicating its prevalence between 44 and 58% among lipedema patients.[11] [34] Additionally, the condition may manifest with telangiectasia, giving the skin a threadlike appearance of dilated blood vessels, and cold extremities.[34] [Table 3] details the clinical characteristics of lipedema patients, highlighting key symptoms and diagnostic features. Obesity is a prevalent comorbidity in lipedema, with its progression closely tied to the worsening of lipedema symptoms. Bertsch and Erbacher found that 88% of their patients had obesity (BMI > 30 kg/m2), suggesting that patients of average weight are rare. However, contrasting findings indicate that 40% of patients had a normal BMI, yet exhibited significant disproportion between their upper and lower bodies.[34] [71]




A) Criteria of Wold et al[1] 1) Bilateral and symmetrical involvement of lower limbs, except the feet 2) Nonpitting edema 3) Painful, tender, and easily bruised 4) Unresponsive to diet and weight reduction interventions 5) Unresponsive to diet and weight reduction interventions |
B) Physical exam Proximal lower limb 1) Disproportionate fat arrangement with the body above the waist (“riding breeches”) 2) Thick cutaneous fat in a circumferential fashion Distal lower limb 1) Proximal subcutaneous fat thickness 2) Distal subcutaneous fat thickness, sparing the feet, creating a sharp demarcation known as the “cuff sign” Proximal upper limb 1) Significant fat accumulation (“angel wing sing”) 2) Abrupt stop at the elbows Distal upper limb 1) Distal subcutaneous fat thickness, sparing the hands (“handcuff sign”) |
C) Extra criteria 1) Pain with bimanual palpation 2) Distal fat tissue tendrils of the knee |
Diagnosing lipedema is challenging, often leading to misdiagnosis. To address this, diagnostic criteria were established to enhance clinical suspicion. Initially, Wold et al introduced key determinants for narrowing down differentials.[1] Subsequently, the Dutch work group developed comprehensive guidelines that include the Wold et al criteria[1] physical examination findings, and additional criteria, detailed in [Table 1]. A diagnosis of lipedema is highly probable when all five criteria from Wold et al and two physical examination findings are present. If these criteria are not fully met, the presence of any two additional criteria may still support a diagnosis.
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Differential Diagnoses
Several conditions are frequently confused with lipedema, which are lymphedema, obesity, and venous insufficiency; therefore, the distinction between them is crucial to reaching the correct diagnosis.[32] [40]
Lymphedema
Lymphedema involves lymphatic drainage dysfunction leading to limb swelling from lymph accumulation, whereas lipedema stems from localized adipose tissue deposition.[15] [40] Clinically, lymphedema initiates distally and unilaterally with a possible Stemmer's sign, which, when positive, means the inability to pinch and lift a fold of skin at the base of the second toe or finger. Lipedema is bilateral, spares feet, causes pain/bruising, and lacks Stemmer's sign.[15] [40] [Table 4] provides an overview of the clinical disparities observed between the two conditions. Imaging aids diagnosis. Ultrasound shows increased subcutaneous thickness and decreased echogenicity in lymphedema, whereas lipedema has normal thickness and echogenicity.[33] [40] MRI offers high sensitivity in differentiating the conditions. Both MRI and CT reveal homogenous subcutaneous fat thickening in lipedema versus fluid accumulation and honeycombing with muscle hypertrophy in lymphedema.[32] [40] Other modalities, such as indocyanine green lymphography (ICG) lymphography and scintigraphy, show normal or increased lymphatic function in lipedema. Additionally, the tissue dielectric constant and DEXA can provide further distinction if ambiguity remains.[32] [40]
ICG offers a pivotal diagnostic approach for lymphoedema by employing a medical dye to map lymphatic flow, highlighting the efficiency or dysfunction within the system. This method visualizes lymphatic transport, distinguishing between normal and pathological conditions, such as dermal backflow in lymphoedema cases. ICG Lymphography's ability to assess lymphatic functionality in real-time is crucial for developing targeted treatment plans.[72]
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Obesity and Localized Areas of Fat Deposition
Differentiating lipedema from obesity is challenging as it can co-occur. However, the key distinction is that obesity improves with lifestyle changes like diet and exercise, whereas lipedema does not. Also, obesity has a more proportional fat distribution compared with lipedema's isolated limb involvement.[15] [32] [40] Localized adiposity in obesity can resemble lipedema but is more responsive to interventions. Dercum's disease and Madelung's diseases are rare adipose disorders with distinct features, such as multiple lipomas or male predisposition.[32] [40] Lipedema's poor responsiveness to weight loss and disproportionate fat distribution help distinguish it from generalized or localized obesity.
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Venous Insufficiency
Chronic venous disease (CVD) is another condition confused with lipedema.[32] However, CVD has distinct features like skin discoloration, varicose veins, pitting edema, and ulceration that improve with interventions like elevation, compression, and exercise. Lipedema lacks these hallmarks. Though varicose veins occur in both conditions, a history of ulceration or cellulitis makes CVD more likely. Additionally, cellulitis is frequently associated with lymphatic dysfunction.[32] [40] Overall, the amenability of CVD signs to treatment versus lipedema's resistance helps differentiate the two.
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Psychosocial Impact
Lipedema profoundly impacts quality of life, including physical, emotional, and social functioning.[8] [29] [41] [55] [73] Clarke et al found that patients with advanced lipedema (stages 3 and 4) reported significantly higher rates of mobility issues, pain, fatigue, and work problems compared with those with early-stage lipedema (stages 1 and 2). Advanced-stage patients also experienced more mental health issues, including depression and feelings of isolation.[41] Misdiagnosis is common, with 41% diagnosed after age 40.[41] [48] Lipedema dismissal as an “invalid condition” was reported by 30%.[41] Due to misperception of obesity, lifestyle modifications are often advised, leading to self-doubt when ineffective. One study found that patients felt that doctors' advice on diet/exercise reflected ignorance, further postponing diagnosis/treatment.[49] Healthcare weight stigma and misinformation must be addressed given their detrimental impacts on care and psychological outcomes.[41] [74] Disease progression impairs mobility and independence due to accumulating joint deterioration, pain, and fatigue.[9] [39] [40] [41] A study of stages 3 and 4 patients revealed significant mobility/activity limitations affecting work.[41] [75] More support may be needed in the late stages to maintain functioning. Psychological distress varies by stage. Failed weight loss efforts in adolescence often trigger long-term cycles of eating disorders in up to 18% of individuals.[41] [54] [76] [77] Depression prevalence ranges from 31 to 59%,[41] [54] [76] [77] higher with a BMI ≥ 40.[77] Perceived unmanaged symptoms like pain also worsen anxiety and depression.[59] Despite profound impacts, the current quality of life is considered moderate.[39]
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Treatment Approaches
Lipedema's complex, poorly understood pathophysiology, and limited therapeutic options pose significant clinical challenges. Patient education is crucial to align expectations with available management approaches, which aim to relieve symptoms, improve functioning, slow progression, and emphasize secondary prevention.[32] [45] Various specialties, including plastic surgery, vascular surgery, and rehabilitation, diagnose and treat lipedema across countries.[70] The inability to cure lipedema represents a major global challenge requiring further research.[70] A multimodal approach encompassing psychosocial support, education, and family planning.[34] The mainstays of treatment include conservative measures and surgical procedures.[40] [Tables 5] and [6] outline the classification, assessment, and treatment options for lipedema, providing a structured approach to management strategies.
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Conservative Strategies
Standard conservative therapy for lipedema includes dietary counseling, manual therapy, compression garments, pneumatic compression devices, and home exercise plans.[20]
Decongestive Therapy
Complex decongestive therapy (CDT) is used for both lipedema and lymphedema but shows limited benefit in pure lipedema without fluid excess or lymphatic dysfunction.[34] Guidelines propose CDT as a first-line conservative treatment,[30] though its components—exercise, compression bandaging, manual lymph drainage, and skincare—only reduce limb circumference by up to 10%.[30] Pneumatic compression augments CDT by improving venous return and can be used at home when combined with patient education.[78] Overall, CDT may offer mild improvements in lipedema but is likely more effective for concurrent lymphedema.
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Compression Therapy
Compression garments streamline limb shape and reduce lipedema symptoms like heaviness, pain, and edema.[69] [70] Decongestive bandaging should precede compression in active edema. Compression does not reduce fat but can prevent new edema while improving lymphatic/venous flow to alleviate associated problems.[32] Daily compression use is critical for maintaining CDT benefits and improving symptoms and function. However, only 38% of patients comply, likely due to skin sensitivity. Compression provides symptomatic relief but requires careful introduction and consistent use to optimize efficacy.[78] [79]
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Massage
Subcutaneous adipose tissue therapy, known as quadrivas therapy, utilizes deep scraping and hook massage techniques to stimulate microcirculation. The therapy has significantly reduced weight, leg fat mass, and total leg volume in patients.[30]
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Physical Activity
Physical activity in lipedema should aim to achieve realistic weight loss and control symptoms. Exercise preferentially affects the arms versus legs,[69] [80] but increasing leg muscle activity can improve lymphatic drainage and prevent edema—additional well-being, self-esteem, mobility, and strength.[34]
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Dietary Program
Dietary changes alone cannot reduce lipedema fat accumulation but may improve prognosis and well-being when combined with obesity management.[81] [82] [83] Early weight loss and diet modifications could lessen inflammation, preventing symptom deterioration.[57] Diet should be combined with lifestyle changes like exercise, walking, swimming, and compression.[29] [40] Overall, while unable to directly treat lipedema, dietary interventions play a supportive role in managing secondary obesity and inflammation. While no specific diet is approved for lipedema, nutrition remains an important component of treatment.[40] Some evidence suggests ketogenic diets may aid lipolysis.[39] One case study described substantial weight loss (−41 kg) and reduced limb circumference in a patient on a long-term ketogenic diet, who also reported improved pain and quality of life after declining other treatments.[42] This example illustrates the potential of customized ketogenic diet plans for lipedema management. The Mediterranean diet, abundant in fruits and vegetables and characterized by a reduced carbohydrate intake of around 40% of total calories, has shown partial effectiveness in managing lipedema. This benefit is likely due to better blood sugar control from reduced carbohydrates and increased fiber. Moreover, the diet's rich content of vitamins and polyphenols, which have recognized epigenetic effects, contributes to its health benefits. These factors help reduce inflammation and improve metabolic health, potentially alleviating some symptoms of lipedema.[42] Overall, nutrition is adjunctive, and individualized dietary plans like ketogenic diets warrant further research.
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Surgical Interventions for lipedema
Conservative management should precede surgical options.[33] Surgery is the only treatment that reduces lipedema fat, decreases volume and prevents mechanical impairment.[40] The two main surgeries are liposuction and lipectomy, with liposuction being the most common.[32] However, surgery, especially liposuction, is costly.[33] Some advise against surgery due to risks of subsequent lymphedema ([Fig. 3]).[57] [84]


Liposuction
Multiple liposuction techniques have been developed, each offering distinct advantages. Initially, dry liposuction, prevalent before the 1990s and performed under general anesthesia, was associated with lymphatic damage, edema, and bleeding. In contrast, wet liposuction techniques, including tumescent, super wet, and wet liposuction, involve the infiltration of fluid before aspiration. This approach helps preserve the lymphatics and reduces complications, making wet liposuction, which uses a combination of vasoconstrictor and anesthetic in saline, safer and less traumatic compared with dry liposuction.[34] [85] Among these, tumescent liposuction is regarded as the gold standard, efficiently removing fat with minimal impact on lymphatics.[15] It is subdivided into water-jet-assisted and vibration-assisted techniques, with the latter being more prevalent and further minimizing tissue injury.[86] [87] For younger, nonobese patients, laser-assisted liposuction offers superior outcomes in terms of skin tightening and limb contouring. However, its effectiveness is less pronounced in elderly patients with lipedema.[30] Mega-liposuction, which requires careful monitoring of fluid and electrolytes, presents another option.[34] Undergoing multiple liposuction sessions may also contribute to an improved overall health status.[44] A study involving 85 lipedema patients demonstrated the long-term effectiveness of liposuction through a questionnaire evaluation.[40] To address lymphatic damage, specific techniques such as tumescent liposuction and the use of small cannulae are employed for treating lipedema.[53] A recent study by Mortada et al assessed various liposuction modalities in managing lipedema and found that only a small percentage of patients (0.18%) developed secondary lymphedema following the procedure.[88] Yamamoto et al demonstrated the use of ICG lymphography to visualize and preserve main lymph flows during leg lipectomy procedures, potentially reducing postoperative complications such as seroma and wound dehiscence.[52] Additionally, mapping the lymphatics using ICG lymphography during surgery helps visualize and thus minimize lymphatic damage, aiming to reduce the risk of secondary lymphedema.[52] [89] [90] Given the potential complications, these procedures should ideally be performed by experienced professionals. After the removal of excess fat from the body, patients have reported decreased pain, muscle contractions, tightness, itching, swelling, and bruising, as well as improved physical appearance. Surgical management decreases bulkiness and enhances ambulation biomechanics. In addition, a few studies have shown an increase in life satisfaction, including reduced ache, fullness, and weariness, along with improvements in physical health conditions and mental well-being in general. Nevertheless, it is worth noting that liposuction is very costly.[28] [36]
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Lipectomy
Lipectomy is a more invasive debulking procedure involving the excision of substantial localized fat deposits. It is reserved for advanced lipedema with severe mechanical impairment or limb abnormalities.[34] Factors like patient age, disease duration, and length of conservative therapy do not appear to significantly impact surgical outcomes.[32]
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Emerging Approaches: Pharmacotherapy and Devices
While no single pharmacological agent is approved for lipedema, drugs can address associated symptoms and complications. Goals include minimizing pain, swelling, fibrosis, inflammation, and preventing venous disease and secondary lymphedema.[34] [47] Metformin and resveratrol may prevent fibrosis and inflammation. Metformin benefits those with metabolic abnormalities. Sympathomimetics like amphetamine promote lipolysis through adrenoreceptors on vessels.[8] [18] [91] Diosmin reduces swelling from chronic venous insufficiency. Selenium improves inflammation and leg volume.[8] [18] [91] Drugs causing fluid retention should be avoided. Furosemide increases interstitial proteins, impeding fluid removal.[20] [33] When appropriate, home pneumatic compression can better control swelling, pain, and lymph flow versus self-manual drainage, and reduces postoperative DVT risk when combined with early mobilization.[92] [93] [94]
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Future Directions
Several critical knowledge gaps remain in lipedema pathophysiology. While chronic inflammation is a known hallmark, the specific inflammatory pathways driving adipose expansion, immune responses, and angiogenesis require further elucidation to identify therapeutic targets.[30] [45] The mechanisms underlying the predominant lower extremity adipose distribution are unclear and warrant investigation.[45] The factors driving lipedema progression from early to advanced stages are unclear and require study to enable targeted interventions.[41] Risk factors like genetics and environment are uncertain despite suspected heritability.[48] Altered estrogen receptor content implies sex hormone involvement but needs further research.[51] Comorbidities with lymphedema and obesity add complexity.[15] [30] [33] Bridging knowledge gaps in lipedema pathogenesis will enable the evolution of more effective future management strategies and enhanced quality of life for those affected.
Further investigation into the pathogenesis of lipedema is crucial, focusing on inflammatory pathways, molecular mechanisms driving adipose deposition, determinants of disease progression, and identification of risk factors. Improving diagnosis and awareness is paramount for patients with this condition's well-being. This will require establishing standardized diagnostic criteria, epidemiological studies, and initiatives to educate healthcare professionals. Additionally, optimizing treatment strategies and patient support should involve personalized approaches, longitudinal studies on surgical interventions, and integration of psychosocial support into patient care. Multidisciplinary approaches and a holistic understanding of lipedema are vital for improving early recognition, access to care, and overall quality of life for individuals affected by this complex condition. By addressing these recommendations, future research can contribute to developing more effective strategies for managing and treating lipedema, ultimately enhancing the well-being of those impacted by this challenging disorder.
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Conclusion
According to the studies included in this review, lipedema is a frequently misdiagnosed and underdiagnosed disease, characterized by disproportionate fat accumulation, primarily affecting the lower limbs, and having a far greater prevalence in women. The condition is associated with hormonal influences and genetic and demographic factors, though further research is needed to understand its pathogenesis and interplay with lymphedema and obesity. Treatment approaches for lipedema include surgical interventions, conservative strategies, emerging therapies, and multidisciplinary care.
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Conflict of Interest
H.M. and J.P.H. are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Acknowledgment
We would like to express our deepest gratitude to all the authors and researchers whose significant contributions in the form of previously published papers and studies have made this work possible. The breadth and depth of the insights presented in their work have been instrumental in shaping our research. Their meticulous efforts and pioneering work in this field have provided a solid foundation upon which our study stands. Their contributions to the body of knowledge surrounding this topic are not only appreciated but crucial for the advancement of this field of study. It is our honor to build upon their work and continue the dialogue that they have so capably initiated.
Ethics Approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted was waived due to the nature of the study.
Authors' Contributions
H.M. conceptualized the study, conducted the literature review, and drafted the manuscript. A.W.A. and N.Z.A. assisted with data collection and analysis. R.K.S. and G.A.A. contributed to manuscript revision and critical review. J.P.H. provided expert input on surgical management and edited the final draft. F.A. supervised the project, finalized the manuscript, and served as the corresponding author. All authors approved the final version.
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- 25 Microlymphatic aneurysms in patients with lipedema. . Accessed Feb 23, 2024 at: https://www.researchgate.net/publication/11573924_microlymphatic_aneurysms_in_patients_with_lipedema
- 26 Tarbell JM, Simon SI, Curry FRE. Mechanosensing at the vascular interface. Annu Rev Biomed Eng 2014; 16 (16) 505-532
- 27 Todd M. Lipoedema: presentation and management. Br J Community Nurs 2010; 15 (Suppl. 04) S10-S16
- 28 Dadras M, Mallinger PJ, Corterier CC, Theodosiadi S, Ghods M. Liposuction in the treatment of lipedema: a longitudinal study. Arch Plast Surg 2017; 44 (04) 324-331
- 29 Tuğral A, Bakar Y. An approach to lipedema: a literature review of current knowledge of an underestimated health problem. Eur J Plast Surg 2019; 42: 549-558
- 30 Wollina U. Lipedema-an update. Dermatol Ther 2019; 32 (02) e12805
- 31 Poojari A, Dev K, Rabiee A. Lipedema: insights into morphology, pathophysiology, and challenges. Biomedicines 2022; 10 (12) 3081
- 32 Warren Peled A, Kappos EA. Lipedema: diagnostic and management challenges. Int J Womens Health 2016; 8: 389-395
- 33 Vyas A, Ghufran A. Continuing Education Activity. Available at: https://www.ncbi.nlm.nih.gov/books/nbk573066/?report=printable (Accessed on December 19, 2023)
- 34 Forner-Cordero I, Forner-Cordero A, Szolnoky G. Update in the management of lipedema. Int Angiol 2021; 40 (04) 345-357
- 35 Esmer M, Schingale FJ, Unal D, Yazıcı MV, Güzel NA. Physiotherapy and rehabilitation applications in lipedema management: a literature review. Lymphology 2020; 53 (02) 88-95
- 36 Peprah K, MacDougall D. Liposuction for the Treatment of Lipedema: A Review of Clinical Effectiveness and Guidelines. Liposuction for the Treatment of Lipedema: A Review of Clinical Effectiveness and Guidelines. Accessed June 7, 2019 at: https://www.ncbi.nlm.nih.gov/books/nbk545818/
- 37 Tran K, Horton J. Liposuction for Lipedema: 2022 Update: Rapid Review. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2022. Aug. Available at: https://www.ncbi.nlm.nih.gov/books/NBK603381/
- 38 Duhon BH, Phan TT, Taylor SL, Crescenzi RL, Rutkowski JM. Current mechanistic understandings of lymphedema and lipedema: tales of fluid, fat, and fibrosis. Int J Mol Sci 2022; 23 (12) 6621
- 39 Alwardat N, Di Renzo L, Alwardat M. et al. The effect of lipedema on health-related quality of life and psychological status: a narrative review of the literature. Eat Weight Disord 2020; 25 (04) 851-856
- 40 Aksoy H, Karadag AS, Wollina U. Cause and management of lipedema-associated pain. Dermatol Ther 2021; 34 (01) e14364
- 41 Clarke C, Kirby JN, Smidt T, Best T. Stages of lipoedema: experiences of physical and mental health and health care. Qual Life Res 2023; 32 (01) 127-137
- 42 Cannataro R, Michelini S, Ricolfi L. et al. Management of lipedema with ketogenic diet: 22-month follow-up. Life (Basel) 2021; 11 (12) 1402
- 43 Schlosshauer T, Heiss C, von Hollen AK, Spennato S, Rieger UM. Liposuction treatment improves disease-specific quality of life in lipoedema patients. Int Wound J 2021; 18 (06) 923-931
- 44 Bouillon VN, Hinson CS, Hu M, Brooks RM. Management of lipedema beyond liposuction: a case study. Aesthet Surg J Open Forum 2023; 5: ojad088
- 45 Podda M, Kovacs M, Hellmich M. et al. A randomised controlled multicentre investigator-blinded clinical trial comparing efficacy and safety of surgery versus complex physical decongestive therapy for lipedema (LIPLEG). Trials 2021; 22 (01) 758
- 46 Amato ACM, Amato FCM, Amato JLS, Benitti DA. Lipedema prevalence and risk factors in Brazil. J Vasc Bras 2022; 21: e20210198
- 47 Czerwińska M, Teodorczyk J, Hansdorfer-Korzon R. A scoping review of available tools in measurement of the effectiveness of conservative treatment in lipoedema. Int J Environ Res Public Health 2022; 19 (12) 7124
- 48 Falck J, Rolander B, Nygårdh A, Jonasson LL, Mårtensson J. Women with lipoedema: a national survey on their health, health-related quality of life, and sense of coherence. BMC Womens Health 2022; 22 (01) 457
- 49 Melander C, Juuso P, Olsson M. Women's experiences of living with lipedema. Health Care Women Int 2022; 43 (1–3): 54-69
- 50 Amato ACM, Benitti DA. Lipedema can be treated non-surgically: a report of 5 cases. Am J Case Rep 2021; 22 (01) e934406
- 51 Bertlich M, Jakob M, Bertlich I, Schift R, Bertlich R. Lipedema in a male patient: report of a rare case - management and review of the literature. GMS Interdiscip Plast Reconstr Surg DGPW 2021; 10: Doc11
- 52 Yamamoto T, Yamashita M, Furuya M, Hayashi A. Lymph preserving lipectomy under indocyanine green lymphography navigation. J Plast Reconstr Aesthet Surg 2015; 68 (01) 136-137
- 53 van de Pas CB, Boonen RSM, Stevens S, Willemsen S, Valkema R, Neumann M. Does tumescent liposuction damage the lymph vessels in lipoedema patients?. Phlebology 2020; 35 (04) 231-236
- 54 Romeijn JRM, de Rooij MJM, Janssen L, Martens H. Exploration of patient characteristics and quality of life in patients with lipoedema using a survey. Dermatol Ther (Heidelb) 2018; 8 (02) 303-311
- 55 Langendoen SI, Habbema L, Nijsten TEC, Neumann HAM. Lipoedema: from clinical presentation to therapy. a review of the literature. Br J Dermatol 2009; 161 (05) 980-986
- 56 Godoy MdeF, Buzato E, Brigidio PAF, Pereira de Godoy JM. Is lymphostasis an aggravant of lipedema?. Case Rep Dermatol 2012; 4 (03) 222-226
- 57 Suga H, Araki J, Aoi N, Kato H, Higashino T, Yoshimura K. Adipose tissue remodeling in lipedema: adipocyte death and concurrent regeneration. J Cutan Pathol 2009; 36 (12) 1293-1298
- 58 Kim JH, Kim JH, Lee YM, Ahn EM, Kim KW, Yu YS. Decursin inhibits retinal neovascularization via suppression of VEGFR-2 activation. Mol Vis 2009; 15: 1868-1875
- 59 Siems W, Grune T, Voss P, Brenke R. Anti-fibrosclerotic effects of shock wave therapy in lipedema and cellulite. Biofactors 2005; 24 (1-4): 275-282
- 60 Paolacci S, Precone V, Acquaviva F. et al. GeneOb Project. Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. Eur Rev Med Pharmacol Sci 2019; 23 (13) 5581-5594
- 61 Bano G, Mansour S, Brice G. et al. Pit-1 mutation and lipoedema in a family. Exp Clin Endocrinol Diabetes 2010; 118 (06) 377-380
- 62 Precone V, Barati S, Paolacci S. et al. Genetic syndromes with localized subcutaneous fat tissue accumulation. Acta Biomedica 2019; 90 (Suppl. 10) 90-92
- 63 Zechner U, Kohlschmidt N, Kempf O. et al. Familial Sotos syndrome caused by a novel missense mutation, C2175S, in NSD1 and associated with normal intelligence, insulin dependent diabetes, bronchial asthma, and lipedema. Eur J Med Genet 2009; 52 (05) 306-310
- 64 Waxler JL, Guardino C, Feinn RS, Lee H, Pober BR, Stanley TL. Altered body composition, lipedema, and decreased bone density in individuals with Williams syndrome: a preliminary report. Eur J Med Genet 2017; 60 (05) 250-256
- 65 Zhang Y, Nadeau M, Faucher F. et al. Progesterone metabolism in adipose cells. Mol Cell Endocrinol 2009; 298 (1-2): 76-83
- 66 Halk AB, Damstra RJ. First Dutch guidelines on lipedema using the international classification of functioning, disability and health. Phlebology 2017; 32 (03) 152-159
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- 68 Lontok ET. Lipedema: A Giving Smarter Guide. Available at: https://www.researchgate.net/publication/314134271 (Accessed on December 19, 2023)
- 69 Book Review. Lipedema - The Disease They Call Fat - Lymphoedema Education Solutions. . Accessed Feb 23, 2024 at: https://lymphoedemaeducation.com.au/2017/11/book-review-lipedema-disease-call-fat/
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- 94 Bellini E, Grieco MP, Raposio E. A journey through liposuction and liposculture: review. Ann Med Surg (Lond) 2017; 24: 53-60
Address for correspondence
Publication History
Received: 19 June 2024
Accepted: 17 January 2025
Accepted Manuscript online:
11 February 2025
Article published online:
15 May 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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- 24 Földi E, Földi M, Tischendorf F. Adipositas, lipedema and lymphostasis. Med Welt 1983; 34 (07) 198-200
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- 26 Tarbell JM, Simon SI, Curry FRE. Mechanosensing at the vascular interface. Annu Rev Biomed Eng 2014; 16 (16) 505-532
- 27 Todd M. Lipoedema: presentation and management. Br J Community Nurs 2010; 15 (Suppl. 04) S10-S16
- 28 Dadras M, Mallinger PJ, Corterier CC, Theodosiadi S, Ghods M. Liposuction in the treatment of lipedema: a longitudinal study. Arch Plast Surg 2017; 44 (04) 324-331
- 29 Tuğral A, Bakar Y. An approach to lipedema: a literature review of current knowledge of an underestimated health problem. Eur J Plast Surg 2019; 42: 549-558
- 30 Wollina U. Lipedema-an update. Dermatol Ther 2019; 32 (02) e12805
- 31 Poojari A, Dev K, Rabiee A. Lipedema: insights into morphology, pathophysiology, and challenges. Biomedicines 2022; 10 (12) 3081
- 32 Warren Peled A, Kappos EA. Lipedema: diagnostic and management challenges. Int J Womens Health 2016; 8: 389-395
- 33 Vyas A, Ghufran A. Continuing Education Activity. Available at: https://www.ncbi.nlm.nih.gov/books/nbk573066/?report=printable (Accessed on December 19, 2023)
- 34 Forner-Cordero I, Forner-Cordero A, Szolnoky G. Update in the management of lipedema. Int Angiol 2021; 40 (04) 345-357
- 35 Esmer M, Schingale FJ, Unal D, Yazıcı MV, Güzel NA. Physiotherapy and rehabilitation applications in lipedema management: a literature review. Lymphology 2020; 53 (02) 88-95
- 36 Peprah K, MacDougall D. Liposuction for the Treatment of Lipedema: A Review of Clinical Effectiveness and Guidelines. Liposuction for the Treatment of Lipedema: A Review of Clinical Effectiveness and Guidelines. Accessed June 7, 2019 at: https://www.ncbi.nlm.nih.gov/books/nbk545818/
- 37 Tran K, Horton J. Liposuction for Lipedema: 2022 Update: Rapid Review. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2022. Aug. Available at: https://www.ncbi.nlm.nih.gov/books/NBK603381/
- 38 Duhon BH, Phan TT, Taylor SL, Crescenzi RL, Rutkowski JM. Current mechanistic understandings of lymphedema and lipedema: tales of fluid, fat, and fibrosis. Int J Mol Sci 2022; 23 (12) 6621
- 39 Alwardat N, Di Renzo L, Alwardat M. et al. The effect of lipedema on health-related quality of life and psychological status: a narrative review of the literature. Eat Weight Disord 2020; 25 (04) 851-856
- 40 Aksoy H, Karadag AS, Wollina U. Cause and management of lipedema-associated pain. Dermatol Ther 2021; 34 (01) e14364
- 41 Clarke C, Kirby JN, Smidt T, Best T. Stages of lipoedema: experiences of physical and mental health and health care. Qual Life Res 2023; 32 (01) 127-137
- 42 Cannataro R, Michelini S, Ricolfi L. et al. Management of lipedema with ketogenic diet: 22-month follow-up. Life (Basel) 2021; 11 (12) 1402
- 43 Schlosshauer T, Heiss C, von Hollen AK, Spennato S, Rieger UM. Liposuction treatment improves disease-specific quality of life in lipoedema patients. Int Wound J 2021; 18 (06) 923-931
- 44 Bouillon VN, Hinson CS, Hu M, Brooks RM. Management of lipedema beyond liposuction: a case study. Aesthet Surg J Open Forum 2023; 5: ojad088
- 45 Podda M, Kovacs M, Hellmich M. et al. A randomised controlled multicentre investigator-blinded clinical trial comparing efficacy and safety of surgery versus complex physical decongestive therapy for lipedema (LIPLEG). Trials 2021; 22 (01) 758
- 46 Amato ACM, Amato FCM, Amato JLS, Benitti DA. Lipedema prevalence and risk factors in Brazil. J Vasc Bras 2022; 21: e20210198
- 47 Czerwińska M, Teodorczyk J, Hansdorfer-Korzon R. A scoping review of available tools in measurement of the effectiveness of conservative treatment in lipoedema. Int J Environ Res Public Health 2022; 19 (12) 7124
- 48 Falck J, Rolander B, Nygårdh A, Jonasson LL, Mårtensson J. Women with lipoedema: a national survey on their health, health-related quality of life, and sense of coherence. BMC Womens Health 2022; 22 (01) 457
- 49 Melander C, Juuso P, Olsson M. Women's experiences of living with lipedema. Health Care Women Int 2022; 43 (1–3): 54-69
- 50 Amato ACM, Benitti DA. Lipedema can be treated non-surgically: a report of 5 cases. Am J Case Rep 2021; 22 (01) e934406
- 51 Bertlich M, Jakob M, Bertlich I, Schift R, Bertlich R. Lipedema in a male patient: report of a rare case - management and review of the literature. GMS Interdiscip Plast Reconstr Surg DGPW 2021; 10: Doc11
- 52 Yamamoto T, Yamashita M, Furuya M, Hayashi A. Lymph preserving lipectomy under indocyanine green lymphography navigation. J Plast Reconstr Aesthet Surg 2015; 68 (01) 136-137
- 53 van de Pas CB, Boonen RSM, Stevens S, Willemsen S, Valkema R, Neumann M. Does tumescent liposuction damage the lymph vessels in lipoedema patients?. Phlebology 2020; 35 (04) 231-236
- 54 Romeijn JRM, de Rooij MJM, Janssen L, Martens H. Exploration of patient characteristics and quality of life in patients with lipoedema using a survey. Dermatol Ther (Heidelb) 2018; 8 (02) 303-311
- 55 Langendoen SI, Habbema L, Nijsten TEC, Neumann HAM. Lipoedema: from clinical presentation to therapy. a review of the literature. Br J Dermatol 2009; 161 (05) 980-986
- 56 Godoy MdeF, Buzato E, Brigidio PAF, Pereira de Godoy JM. Is lymphostasis an aggravant of lipedema?. Case Rep Dermatol 2012; 4 (03) 222-226
- 57 Suga H, Araki J, Aoi N, Kato H, Higashino T, Yoshimura K. Adipose tissue remodeling in lipedema: adipocyte death and concurrent regeneration. J Cutan Pathol 2009; 36 (12) 1293-1298
- 58 Kim JH, Kim JH, Lee YM, Ahn EM, Kim KW, Yu YS. Decursin inhibits retinal neovascularization via suppression of VEGFR-2 activation. Mol Vis 2009; 15: 1868-1875
- 59 Siems W, Grune T, Voss P, Brenke R. Anti-fibrosclerotic effects of shock wave therapy in lipedema and cellulite. Biofactors 2005; 24 (1-4): 275-282
- 60 Paolacci S, Precone V, Acquaviva F. et al. GeneOb Project. Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. Eur Rev Med Pharmacol Sci 2019; 23 (13) 5581-5594
- 61 Bano G, Mansour S, Brice G. et al. Pit-1 mutation and lipoedema in a family. Exp Clin Endocrinol Diabetes 2010; 118 (06) 377-380
- 62 Precone V, Barati S, Paolacci S. et al. Genetic syndromes with localized subcutaneous fat tissue accumulation. Acta Biomedica 2019; 90 (Suppl. 10) 90-92
- 63 Zechner U, Kohlschmidt N, Kempf O. et al. Familial Sotos syndrome caused by a novel missense mutation, C2175S, in NSD1 and associated with normal intelligence, insulin dependent diabetes, bronchial asthma, and lipedema. Eur J Med Genet 2009; 52 (05) 306-310
- 64 Waxler JL, Guardino C, Feinn RS, Lee H, Pober BR, Stanley TL. Altered body composition, lipedema, and decreased bone density in individuals with Williams syndrome: a preliminary report. Eur J Med Genet 2017; 60 (05) 250-256
- 65 Zhang Y, Nadeau M, Faucher F. et al. Progesterone metabolism in adipose cells. Mol Cell Endocrinol 2009; 298 (1-2): 76-83
- 66 Halk AB, Damstra RJ. First Dutch guidelines on lipedema using the international classification of functioning, disability and health. Phlebology 2017; 32 (03) 152-159
- 67 Schmeller W, Meier-Vollrath I. Lipödem - Aktuelles zu einem weitgehend unbekannten krankheitsbild. Aktuelle Derm 2007; 33 (07) 251-260
- 68 Lontok ET. Lipedema: A Giving Smarter Guide. Available at: https://www.researchgate.net/publication/314134271 (Accessed on December 19, 2023)
- 69 Book Review. Lipedema - The Disease They Call Fat - Lymphoedema Education Solutions. . Accessed Feb 23, 2024 at: https://lymphoedemaeducation.com.au/2017/11/book-review-lipedema-disease-call-fat/
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