Characterizing Lower Extremity Lymphedema and Lipedema with Cutaneous Ultrasonography and an Objective Computer-Assisted Measurement of Dermal Echogenicity

Iker, Emily; Mayfield, Cory K.; Gould, Daniel J.; Patel, Ketan M.

doi:10.1089/lrb.2017.0090

Cited by 42 publications

(39 citation statements)

References 16 publications

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“…Similar results have been obtained from animal studies, where VEGF-C levels exhibit an approximate 100% increase in the serum of mice with lymphedema versus controls 16 . As such, these results are in line with previous imaging 21,23,25 studies and indicate that in the absence of morbid adiposity the lymphatic and blood vascular systems are morphologically unaltered in lipedema.…”

Section: Discussionsupporting

confidence: 92%

“…The presence of edema, though, has not been verified 22 . Imaging studies and sonography findings in particular could not prove the presence of increased interstitial fluid in lipedema patients 23 . Evaluation of the lymphatic vascular system via MRI lymphangiography in obese lipedema patients revealed microaneurysms without further lymphatic alterations 13 .…”

Section: Discussionmentioning

confidence: 89%

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Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology

Felmerer

Stylianaki

Hollmén

et al. 2020

Sci Rep

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Lipedema is a chronic adipose tissue disorder characterized by the disproportional subcutaneous deposition of fat and is commonly misdiagnosed as lymphedema or obesity. The molecular determinants of the lipedema remain largely unknown and only speculations exist regarding the lymphatic system involvement. The aim of the present study is to characterize the lymphatic vascular involvement in established lipedema. The histological and molecular characterization was conducted on anatomically-matched skin and fat biopsies as well as serum samples from eleven lipedema and ten BMI-matched healthy patients. Increased systemic levels of vascular endothelial growth factor (VEGF)-C (P = 0.02) were identified in the serum of lipedema patients. Surprisingly, despite the increased VEGF-C levels no morphological changes of the lymphatic vessels were observed. Importantly, expression analysis of lymphatic and blood vessel-related genes revealed a marked downregulation of Tie2 (P < 0.0001) and FLT4 (VEGFR-3) (P = 0.02) consistent with an increased macrophage infiltration (P = 0.009), without changes in the expression of other lymphatic markers. Interestingly, a distinct local cytokine milieu, with decreased VEGF-A (P = 0.04) and VEGF-D (P = 0.02) expression was identified. No apparent lymphatic anomaly underlies lipedema, providing evidence for the different disease nature in comparison to lymphedema. The changes in the lymphatic-related cytokine milieu might be related to a modified vascular permeability developed secondarily to lipedema progression. Lipedema is a distinct adipose tissue disorder, affecting primarily women 1. Epidemiological data of large studies are still not available but the prevalence of lipedema is estimated between 7 and 9.7%. Interestingly the prevalence of lipedema in patients referred to lymphatic clinics is increased, estimated as 10-15% 2,3. The mechanisms involved in lipedema development are largely unknown and despite the distinct clinical features the disease is commonly misdiagnosed as obesity or lymphedema. Clinically, lipedema is characterized by the bilateral and symmetrical adipose tissue deposition, mostly of the lower extremities, sparing the feet. The Stemmer sign is negative and the edematous appearance is resistant to diet restrictions, elevation of the extremities or lymphatic drainage 4 .

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 89%

Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology

Felmerer

Stylianaki

Hollmén

et al. 2020

Sci Rep

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“…This does not rule out possible disease effects on muscle function and energy expenditure in lipedema (12). Adipose tissue hypertrophy was recently observed histologically (13,14) in patients with lipedema and is consistent with thick SAT observed on MRI (9) and ultrasound (15,16) throughout the legs. This may be a protective response to a subclinical vascular disease mechanism in lipedema related to sodium dysregulation.…”

Section: Discussionsupporting

confidence: 83%

Upper and Lower Extremity Measurement of Tissue Sodium and Fat Content in Patients with Lipedema

Crescenzi

Donahue

Petersen

et al. 2020

Obesity

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Objective: The aim of this study is to compare tissue sodium and fat content in the upper and lower extremities of participants with lipedema versus controls using magnetic resonance imaging (MRI). Methods: MRI was performed at 3.0 T in females with lipedema (n = 15, age = 43.2 ± 10.0 years, BMI = 30.3 ± 4.4 kg/m 2 ) and controls without lipedema (n = 14, age = 42.8 ± 13.2 years, BMI = 28.8 ± 4.4 kg/m 2 ). Participants were assessed for pain and disease stage. Sodium MRI was performed in the forearm and calf to quantify regional tissue sodium content (TSC, mmol/L). Chemical-shift-encoded water-fat MRI was performed in identical regions for measurement of fat/water (ratio). Results: In the calf, skin TSC (16.3 ± 2.6 vs. 14.4 ± 2.2 mmol/L, P = 0.04), muscle TSC (20.3 ± 3.0 vs. 18.3 ± 1.7 mmol/L, P = 0.03), and fat/water (1.03 ± 0.37 vs. 0.56 ± 0.21 ratio, P < 0.001) were significantly higher in participants with lipedema versus control participants. In the forearm, skin TSC (13.4 ± 3.3 vs. 12.0 ± 2.3 mmol/L, P = 0.2, Cohen's d = 0.50) and fat/water (0.65 ± 0.24 vs. 0.48 ± 0.24 ratio, P = 0.07, Cohen's d = 0.68) demonstrated moderate effect sizes in participants with lipedema versus control participants. Calf skin TSC was significantly correlated with pain (Spearman's rho = 0.55, P = 0.03) and disease stage (Spearman's rho = 0.82, P < 0.001) among participants with lipedema. Conclusions: MRI-measured tissue sodium and fat content are significantly higher in the lower extremities, but not upper extremities, of patients with lipedema compared with BMI-matched controls.Obesity (2020) 28, 907-915.

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“…In light of these findings, imaging techniques may be considered as a useful tool when diagnosis is doubtful or for lipedema staging. Magnetic resonance imaging, computed tomography, and high‐resolution cutaneous ultrasonography have been also used to differentiate lymphedema from lipedema, although these are seldom applied in the clinic .…”

Section: Assessment and Diagnosismentioning

confidence: 99%

Lipedema: A Call to Action!

Buso

Depairon

Tomson

et al. 2019

Obesity

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Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.

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Characterizing Lower Extremity Lymphedema and Lipedema with Cutaneous Ultrasonography and an Objective Computer-Assisted Measurement of Dermal Echogenicity

Cited by 42 publications

References 16 publications

Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology

Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology

Upper and Lower Extremity Measurement of Tissue Sodium and Fat Content in Patients with Lipedema

Lipedema: A Call to Action!

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