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Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.

Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.

PURPOSE: Breast cancer treatment-related lymphedema (BCRL) evaluation is frequently performed using portable measures of limb volume and bioimpedance asymmetry. Here quantitative magnetic resonance imaging (MRI) is applied to evaluate deep and superficial tissue impairment, in both surgical and contralateral quadrants, to test the hypothesis that BCRL impairment is frequently bilateral and extends beyond regions commonly evaluated with portable external devices. METHODS: 3-T MRI was applied to investigate BCRL topographical impairment. Female BCRL (n = 33; age = 54.1 ± 11.2 years; stage = 1.5 ± 0.8) and healthy (n = 33; age = 49.4 ± 11.0 years) participants underwent quantitative upper limb MRI relaxometry (T2), bioimpedance asymmetry, arm volume asymmetry, and physical evaluation. Parametric tests were applied to evaluate study measurements (i) between BCRL and healthy participants, (ii) between surgical and contralateral limbs, and (iii) in relation to clinical indicators of disease severity. Two-sided p-value < 0.05 was required for significance. RESULTS: Bioimpedance asymmetry was significantly correlated with MRI-measured water relaxation (T2) in superficial tissue. Deep muscle (T2 = 37.6 ± 3.5 ms) and superficial tissue (T2 = 49.8 ± 13.2 ms) relaxation times were symmetric in healthy participants. In the surgical limbs of BCRL participants, deep muscle (T2 = 40.5 ± 4.9 ms) and superficial tissue (T2 = 56.0 ± 14.8 ms) relaxation times were elevated compared to healthy participants, consistent with an edematous micro-environment. This elevation was also observed in contralateral limbs of BCRL participants (deep muscle T2 = 40.3 ± 5.7 ms; superficial T2 = 56.6 ± 13.8 ms). CONCLUSIONS: Regional MRI measures substantiate a growing literature speculating that superficial and deep tissue, in surgical and contralateral quadrants, is affected in BCRL. The implications of these findings in the context of titrating treatment regimens and understanding malignancy recurrence are discussed.

OBJECTIVE: Lipedema is characterized by pain, fatigue, and excessive adipose tissue and sodium accumulation of the lower extremities. This case-control study aims to determine whether sodium or vascular dysfunction is present in the central nervous system. METHODS: Brain magnetic resonance imaging was performed at 3 T in patients with lipedema (n = 15) and control (n = 18) participants matched for sex, age, race, and BMI. Standard anatomical imaging and intracranial angiography were applied to evaluate brain volume and vasculopathy, respectively; arterial spin labeling and sodium magnetic resonance imaging were applied to quantify cerebral blood flow (CBF) (milliliters per 100 grams of tissue/minute) and brain tissue sodium content (millimoles per liter), respectively. A Mann-Whitney U test (significance criteria P < 0.05) was applied to evaluate group differences. RESULTS: No differences in tissue volume, white matter hyperintensities, intracranial vasculopathy, or tissue sodium content were observed between groups. Gray matter CBF was elevated (P = 0.03) in patients with lipedema (57.2 ± 9.6 mL per 100 g/min) versus control participants (49.8 ± 9.1 mL per 100 g/min). CONCLUSIONS: Findings provide evidence that brain sodium and tissue fractions are similar between patients with lipedema and control participants and that patients with lipedema do not exhibit abnormal radiological indicators of intracranial vasculopathy or ischemic injury. Potential explanations for elevated CBF are discussed in the context of the growing literature on lipedema symptomatology and vascular dysfunction.

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/m2 ) and controls without lipedema (n = 14, age = 42.8 ± 13.2 years, BMI = 28.8 ± 4.4 kg/m2 ). 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.

Background: Lipedema is a distinct adipose disorder from obesity necessitating awareness as well as different management approaches to address pain and optimize quality of life (QoL). The purpose of this proof-of-principle study is to evaluate the therapeutic potential of physical therapy interventions in women with lipedema. Methods and Results: Participants with Stage 1-2 lipedema and early Stage 0-1 lymphedema (n = 5, age = 38.4 ± 13.4 years, body mass index = 27.2 ± 4.3 kg/m2) underwent nine visits of physical therapy in 6 weeks for management of symptoms impacting functional mobility and QoL. Pre- and post-therapy, participants were scanned with 3 Tesla sodium and water magnetic resonance imaging (MRI), underwent biophysical measurements, and completed questionnaires measuring function and QoL (patient-specific functional scale, PSFS, and RAND-36). Pain was measured at each visit using the 0-10 visual analog scale (VAS). Treatment effect was calculated for all study variables. The primary symptomatology measures of pain and function revealed clinically significant post-treatment improvements and large treatment effects (Cohen's d for pain VAS = -2.5 and PSFS = 4.4). The primary sodium MRI measures, leg skin sodium, and subcutaneous adipose tissue (SAT) sodium, reduced following treatment and revealed large treatment effects (Cohen's d for skin sodium = -1.2 and SAT sodium = -0.9). Conclusions: This proof-of-principle study provides support that persons with lipedema can benefit from physical therapy to manage characteristic symptoms of leg pain and improve QoL. Objective MRI measurement of reduced tissue sodium in the skin and SAT regions indicates reduced inflammation in the treated limbs. Further research is warranted to optimize the conservative therapy approach in lipedema, a condition for which curative and disease-modifying treatments are unavailable.

Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL.

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

PURPOSE: Lipedema is a painful subcutaneous adipose tissue (SAT) disease involving disproportionate SAT accumulation in the lower extremities that is frequently misdiagnosed as obesity. We developed a semiautomatic segmentation pipeline to quantify the unique lower-extremity SAT quantity in lipedema from multislice chemical-shift-encoded (CSE) magnetic resonance imaging (MRI). APPROACH: Patients with lipedema (n=15) and controls (n=13) matched for age and body mass index (BMI) underwent CSE-MRI acquired from the thighs to ankles. Images were segmented to partition SAT and skeletal muscle with a semiautomated algorithm incorporating classical image processing techniques (thresholding, active contours, Boolean operations, and morphological operations). The Dice similarity coefficient (DSC) was computed for SAT and muscle automated versus ground truth segmentations in the calf and thigh. SAT and muscle volumes and the SAT-to-muscle volume ratio were calculated across slices for decades containing 10% of total slices per participant. The effect size was calculated, and Mann-Whitney U test applied to compare metrics in each decade between groups (significance: two-sided P<0.05). RESULTS: Mean DSC for SAT segmentations was 0.96 in the calf and 0.98 in the thigh, and for muscle was 0.97 in the calf and 0.97 in the thigh. In all decades, mean SAT volume was significantly elevated in participants with versus without lipedema (P<0.01), whereas muscle volume did not differ. Mean SAT-to-muscle volume ratio was significantly elevated (P<0.001) in all decades, where the greatest effect size for distinguishing lipedema was in the seventh decade approximately midthigh (r=0.76). CONCLUSIONS: The semiautomated segmentation of lower-extremity SAT and muscle from CSE-MRI could enable fast multislice analysis of SAT deposition throughout the legs relevant to distinguishing patients with lipedema from females with similar BMI but without SAT disease.

BACKGROUND: National survey data exploring the patient experience with lipedema are lacking. METHODS: We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. RESULTS: A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m2. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; p < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; p < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; p < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; p < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; p < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; p < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; p < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; p < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). CONCLUSION: In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.