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Lipedema is a painful disease of subcutaneous adipose tissue (SAT) in women. This study determined whether an advanced pneumatic compression device (APCD) improved lipedema SAT depth, swelling, and pain. Women with lipedema started 20–30 mm Hg compression leggings then were randomized to an APCD (Lympha Press Optimal Plus) group for 30 days (treatment; n = 22) or a no APCD (Control; n = 24) group. APCD treatment significantly reduced left leg volume (3D imaging, LymphaTech; p < 0.043) and fluid in the left (p = 0.0018) and right legs (p = 0.0476; SOZO, bioimpedance spectroscopy); controls showed no change. Treatment significantly decreased extracellular fluid (ECF) and intracellular fluid (ICF) in left (p = 0.0077; p = 0.0060) and right legs (p = 0.0476; p ≤ 0.025), respectively. Only ECF decreased significantly in the left (p < 0.0183) and right legs (p = 0.0009) in controls. SAT depth decreased significantly by ultrasound after treatment at the anterior (p ≤ 0.0234) and medial thigh (p ≤ 0.0052), medial knee (p ≤ 0.0002) and posterior calf (p ≤ 0.0118) but not in controls. All signs and symptoms of lipedema improved in the treatment group including swelling (p = 0.0005) and tenderness (pain) of right (p = 0.0003) and left legs (p < 0.0001); only swelling improved in controls (p = 0.0377). In total, 87.5% of RAND SF-36 quality of life improved after treatment (p ≤ 0.0351) compared to 37.5% in controls (p ≤ 0.0475). APCDs are effective treatment for lipedema.
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