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Lipedema
 symmetrical edema in the lower limbs with fatty
deposits located on hips and thighs
 chronic disease that occurs mostly in females
 hypothesis: estrogen regulated polygenetic disease
leading to vascular and lymphatic abnormalities
causing inflammation affecting peripheral nerves
 main disorders considered for differential diagnosis:
 lymphedema, primary or secondary
 obesity
 lipohypertrophy
 venous edema
Disclosures
 I have no actual or potential conflict of
interest in relation to this
program/presentation
Lipedema stages
Fatty accumulation on hips, thighs, legs later torso
and arms; feet swelling on later stages (III -IV), upper
arm swelling on later stages (III- IV)
 Stage I – “thick legs”, subtle skin indentations on
upright position, soft skin, small fatty nodules
 Stage II – more pronounced skin indentations, fatty
nodules palpable of different sizes, loss of skin
elasticity, superficial hematomas may be present
Lipedema stages
 Stage III – pronounced skin stretching,
prominent hanging fat pads and masses
mostly inner thighs and knees, and
upper arms, hardening of the tissues,
vascular fragility
 Stage IV – large fat masses
and hanging lobules on legs and
arms, varicosities may be present,
variations of skin changes including
trophic, hardening of the skin and
tissues, joint deformities may be
present
Chief complaints
 pain mostly on legs
 easy bruising
 leg and arm swelling
 fatty lumps on legs, abdomen and arms
 heaviness
 weakness
 fatigue, tiredness
 swelling and fatty deposition worsening after puberty,
pregnancies, contraceptive pills
3
2
1
6
0
1
2
3
4
5
6
7
No Pain Mild Moderate Severe
SCORE
INTENSITY
Pain Score
Physical Examination
 symmetric fatty deposition on legs, abdomen, arms
 superficial varicosities may be present
 tenderness to palpation most prominent at pretibial area
 bruises, varicosities
 hypermobile joints
 non-pitting edema, usually feet
are spared
 negative Stemmer sign (thickened
skin at base of 2nd toe or 2nd finger),
positive Stemmer sign in
lipo-lymphedema
Average BMI ≈ 40.44
37.20
41.66 40.43
24.82
57.51
47.42
31.78
44.11
47.37 47.29
32.03
33.65
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
1 2 3 4 5 6 7 8 9 10 11 12
BODYMASSINDEX(BMI)
SUBJECTS
BMI ≥ 25 (obesity)
BMI ≥ 35 with 2 comorbidities -hypertension and DM (morbid obesity)
BMI ≥ 40 (morbid obesity)
Staging I-IV and BMI
47.37 47.29
41.66 40.43 37.20
33.65 32.03 31.78
24.82
57.51
44.11
47.42
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
I II II II II II II II II III III IV
BMI
Stages
Comorbidities
 diabetes mellitus type II, glucose intolerance
 high blood pressure
 obesity
 arthritis mostly osteoarthritis at spine, hips and knees
 thyroid disease; hypothyroidism, goiter, Hashimoto’s
thyroiditis
 fibromyalgia syndrome
Comorbidities
 autoimmune disorders – systemic lupus
erythematosus (SLE), rheumatoid arthritis (RA)
 polycystic ovaries
 irritable bowel syndrome (IBS)
 gluten and lactose intolerance
 breast, cervix malignant neoplasm
 carcinoid tumor, adrenal adenoma
 bronchial asthma
Comorbidities Distribution (n=12)
7
7
5
5
5
4
4
3
3
Hypothyroidism
Osteoarthritis
Hypertension
Hyperhomocystenemia
VitD Deficiency
Hyperlipidemia
Venous Insufficiency
Elevated Liver Enzymes
IgA Deficiency
Comorbidities Distribution (n=12)
2
2
22
2
1
1
Elevated Factor VIII Clotting
Cancer/ Tumor
Adrenal Insufficiency
Fibromyalgia
DM-II/ Glucose Intolerance
Neuropathy
Vit B12 Def
Surgical history
 gastric sleeve
 gastric bypass
 removal of excess skin after bariatric surgery –
abdomen, thigh lift, arms
 hysterectomy
 cholecystectomy
 total knee replacement
 lumbar laminectomy and fusion
Laboratory abnormalities
 Low vitamin D - usually <15 ng/mL (deficiency)
 Elevated CH50 – presence of chronic inflammation
 Elevated homocysteine - an amino acid and
breakdown product of protein metabolism when
present in high concentrations has been linked to an
increased risk of heart attacks and strokes
 Elevated cholesterol and/or triglycerides
 Low HDL, high LDL
 Elevated fasting blood glucose, high A1C
 Low IgG, IgA – immunodeficiency
Laboratory abnormalities
 Elevated IgE - allergies
 Elevated liver enzymes – fatty liver
 Elevated factor VIII clotting activity – risk factor for
deep venous thrombosis (blood clots)
 Elevated creatinine clearance and low eGFR – kidney
insufficiency
 Low hemoglobin level, iron deficiency (low total iron
and ferritin) - anemia
 Low cortisol a.m. level – adrenal insufficiency
Lymphoscintigraphy
 intradermal or subcutaneous radiotracer injection
between toes, fingers
 evaluates the lymph flow, obstruction and
abnormalities of the lymphatic systems
Lymphoscintigraphy
 estimates the uptake of a radiolabeled
tracer (Tc-99m Sulfur colloid) that is
transported into the regional lymph
nodes by the lymphatic system
 routinely performed as part of evaluation of a swollen
limb
 this technique might both determine the underlying
cause of swelling and indicate its pathophysiology
Lymphoscintrigraphy
 Normal serial images
Lymphoscintigraphy findings
 tortuous and enlarged lymphatic
channels
 delay lymphatic flow
 lymph pooling, collaterals
 none visualization of lymph nodes
 enlarged lymph nodes
100% demonstrated lymphatic
abnormalities (n=12)
Venous duplex lower extremities
 venous insufficiency superficial, perforators and/or
deep system – common 92% (n=12)
 deep venous thrombosis – rarely
Abdomen/Pelvis CT scan findings
 Fatty liver, enlarged liver
 Gallstones
 Enlarged pelvic lymph nodes
 Aorto-iliac atherosclerosis
 Hiatal hernia
 Incidental pulmonary nodule
 Constipation
 Adrenal adenoma
 Pancreas fatty atrophy
Echocardiogram
 Left ventricular hypertrophy
 Mild diastolic dysfunction
 Trace, mild aortic and mitral valve regurgitation
 Dilated left atrium
67% (n=6)
Treatment
 Manual lymphatic drainage (MLD) / decongestive
therapy / application of multilayer compression
bandages (foam, short stretch bandages)
 Use of compression garments; stockings, arm sleeves,
Capri 20 – 30 mmHg; micro massaging garments -
better tolerated
 Night garments and inelastic compression garments –
poorly tolerated
 Get proper sleep and exercise
Exercise
 Low impact aerobic exercises
 Underwater exercises
 General stretching
 Strengthening – progressive
resistance – elastic bands,
tubing
 Studies concluded that slowly progressive exercise of varying
modalities is not associated with the development or
exacerbation of lymphedema such as aerobic and strengthening
 In patients with persistent systemic inflammation as seen in
lipedema and lymphedema, regular exercise training lowers
levels of pro-inflammatory cytokines
Chronic Lymphedema
Rockson, S. G. (2013). The Lymphatics and the Inflammatory Response: Lessons
Learned from Human Lymphedema. Lymphatic Research and Biology, 11(3), 117-120.
Diet
Anti-inflammation
 high omega 3 – flaxseed oil,
salmon, walnuts
 green leafy vegetables, celery, beets,
broccoli, blueberries, pineapple
 avoid allergic/sensitive foods
 reduce simple sugars, eggs, dairy,
gluten
Interventions
 Corrections of vitamin deficiencies such as vitamin D,
B12, folate, B6
 Reduction of homocysteine levels with high doses of
vitamin B12, B6 and folate
 Replace minerals i.e. zinc, magnesium
 Antioxidants & anti-inflammation – curcumin,
green tea, resveratrol, vitamin C
Selenium
 antioxidant properties, trigger immune activation
Good source: 1 medium brazilian nut = 95 mcg, 2 nuts
a day.
 Dose: 200 mcg once a day
Bioflavonoids
 essential for the proper absorption
and utilization of vitamin C
 increase the strength of the
capillaries, and help to prevent
hemorrhages and ruptures, while
also building a protective barrier
against infection
 citrus bioflavonoids, diosmin
 Dose: 500mg once to twice a day
N-Acetyl-Cysteine
 restores intracellular levels of one of the body’s most
powerful antioxidant defenses, glutathione
Dose: 1.2 g (1) cap twice a day
Beta 1,3/1,6 glucans
 powerful antioxidant, moderate tissue-damaging
cytokines
 activation of macrophages, neutrophils, and T-cell–
mediated immunity
 assist in ameliorating microbial imbalance – fight
infections
 Foods: cereal β-glucans from oat, barley, wheat and rye;
mushroom β-glucans from shiitake mushrooms
 Dose: 500mg / day on empty stomach with 8 ounce
water
Liposuction
Water-jet assisted (WAL) and tumescent liposuction
 36 y/o female patient underwent WAL for stage I
lipedema with good results, later had a thigh lift for
loose skin. Lymphoscintigraphy showed slightly
prominent lymphatic channels in the ankle joint and
distal calves bilaterally right > left, inguinal lymph
nodes were identified at 11 minutes; and iliac nodes
at the iliac chains visualized bilaterally @ 30
minutes. One year after WAL + diet + exercises
lipedema remained under control.
Conclusion
 Lymphatic abnormalities are evident in early stages
 Wide array of comorbidities are present
 Multiple treatments and interventions – effectiveness
and long-term outcomes are unknown
References
 Blome, C., Augustin, M., Heyer, K., Knöfel, J., Cornelsen, H., Purwins, S., & Herberger, K. (2014). Evaluation of Patient-
relevant Outcomes of Lymphedema and Lipedema Treatment: Development and Validation of a New Benefit Tool.
European Journal of Vascular and Endovascular Surgery, 47(1), 100-107.
 Boursier V., Pecking A., Vignes S. (2004). Comparative analysis of lymphoscintigraphy between lipedema and lower
limb lymphedema. J Mal Vasc, 29(5), 257-61.
 Cuzzone, D. A., Weitman, E. S., Albano, N. J., Ghanta, S., Savetsky, I. L., Gardenier, J. C., . . . Mehrara, B. J. (2014). IL-6
regulates adipose deposition and homeostasis in lymphedema. AJP: Heart and Circulatory Physiology, 306(10).
 Forner-Cordero, I., Szolnoky, G., Forner-Cordero, A., & Kemény, L. (2012). Lipedema: An overview of its clinical
manifestations, diagnosis and treatment of the disproportional fatty deposition syndrome - systematic review. Clinical
Obesity, 2(3-4), 86-95.
 Kwan, M. L., Cohn, J. C., Armer, J. M., Stewart, B. R., & Cormier, J. N. (2011). Exercise in patients with lymphedema: A
systematic review of the contemporary literature. Journal of Cancer Survivorship J Cancer Surviv, 5(4), 320-336.
 Okhovat, J., & Alavi, A. (2014). Lipedema: A Review of the Literature. The International Journal of Lower Extremity
Wounds, 14(3), 262-267.
 Reich-Schupke, S., Altmeyer, P., & Stücker, M. (2012). Thick legs - not always lipedema. JDDG: Journal Der Deutschen
Dermatologischen Gesellschaft, 11(3), 225-233.
 Rockson, S. G. (2013). The Lymphatics and the Inflammatory Response: Lessons Learned from Human Lymphedema.
Lymphatic Research and Biology, 11(3), 117-120.
References
 Rockson, S. G. (2014). Inflammatory Cytokines and the Lymphatic Endothelium. Lymphatic Research and Biology,
12(3), 123-123.
 Schellong SM., Wollina U., Unger L., Machetanz J., Stelzner C. (2013). Leg swelling. Internist (Berl). 54(11), 1294-303.
 Schmeller, W., & Meier-Vollrath, I. (2006). Tumescent Liposuction: A New and Successful Therapy for Lipedema.
Journal of Cutaneous Medicine and Surgery, 10(1), 7-10.
 Stier, H., Ebbeskotte, V., & Gruenwald, J. (2014). Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan.
Nutrition Journal Nutr J, 13(1), 38.
 Stutz, J. J., & Krahl, D. (2008). Water Jet-Assisted Liposuction for Patients with Lipoedema: Histologic and
Immunohistologic Analysis of the Aspirates of 30 Lipoedema Patients. Aesth Plast Surg Aesthetic Plastic Surgery,
33(2), 153-162.
 Szél, E., Kemény, L., Groma, G., & Szolnoky, G. (2014). Pathophysiological dilemmas of lipedema. Medical Hypotheses,
83(5), 599-606.
 Truchetet F., Bonhomme A. (2015). Recognising and treating lipidema OMIM 614103. Ann Dermatol Venereol. 142(8-
9), 523-9.
 Vignes S. (2012) Lipedema: a misdiagnosed entity. J Mal Vasc, 37(4), 213-8.
 Vignes S., Coupé M., Baulieu F., Vaillant L. (2009). Limb lymphedema: Diagnosis, explorations, complications. French
Lymphology Society. J Mal Vasc. 34(5), 314-22.

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Lipedema: a misdiagnosed and misunderstood fatty deposition syndrome

  • 1.
  • 2. Lipedema  symmetrical edema in the lower limbs with fatty deposits located on hips and thighs  chronic disease that occurs mostly in females  hypothesis: estrogen regulated polygenetic disease leading to vascular and lymphatic abnormalities causing inflammation affecting peripheral nerves  main disorders considered for differential diagnosis:  lymphedema, primary or secondary  obesity  lipohypertrophy  venous edema
  • 3. Disclosures  I have no actual or potential conflict of interest in relation to this program/presentation
  • 4. Lipedema stages Fatty accumulation on hips, thighs, legs later torso and arms; feet swelling on later stages (III -IV), upper arm swelling on later stages (III- IV)  Stage I – “thick legs”, subtle skin indentations on upright position, soft skin, small fatty nodules  Stage II – more pronounced skin indentations, fatty nodules palpable of different sizes, loss of skin elasticity, superficial hematomas may be present
  • 5. Lipedema stages  Stage III – pronounced skin stretching, prominent hanging fat pads and masses mostly inner thighs and knees, and upper arms, hardening of the tissues, vascular fragility  Stage IV – large fat masses and hanging lobules on legs and arms, varicosities may be present, variations of skin changes including trophic, hardening of the skin and tissues, joint deformities may be present
  • 6. Chief complaints  pain mostly on legs  easy bruising  leg and arm swelling  fatty lumps on legs, abdomen and arms  heaviness  weakness  fatigue, tiredness  swelling and fatty deposition worsening after puberty, pregnancies, contraceptive pills
  • 7. 3 2 1 6 0 1 2 3 4 5 6 7 No Pain Mild Moderate Severe SCORE INTENSITY Pain Score
  • 8. Physical Examination  symmetric fatty deposition on legs, abdomen, arms  superficial varicosities may be present  tenderness to palpation most prominent at pretibial area  bruises, varicosities  hypermobile joints  non-pitting edema, usually feet are spared  negative Stemmer sign (thickened skin at base of 2nd toe or 2nd finger), positive Stemmer sign in lipo-lymphedema
  • 9. Average BMI ≈ 40.44 37.20 41.66 40.43 24.82 57.51 47.42 31.78 44.11 47.37 47.29 32.03 33.65 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 1 2 3 4 5 6 7 8 9 10 11 12 BODYMASSINDEX(BMI) SUBJECTS BMI ≥ 25 (obesity) BMI ≥ 35 with 2 comorbidities -hypertension and DM (morbid obesity) BMI ≥ 40 (morbid obesity)
  • 10. Staging I-IV and BMI 47.37 47.29 41.66 40.43 37.20 33.65 32.03 31.78 24.82 57.51 44.11 47.42 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 I II II II II II II II II III III IV BMI Stages
  • 11. Comorbidities  diabetes mellitus type II, glucose intolerance  high blood pressure  obesity  arthritis mostly osteoarthritis at spine, hips and knees  thyroid disease; hypothyroidism, goiter, Hashimoto’s thyroiditis  fibromyalgia syndrome
  • 12. Comorbidities  autoimmune disorders – systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)  polycystic ovaries  irritable bowel syndrome (IBS)  gluten and lactose intolerance  breast, cervix malignant neoplasm  carcinoid tumor, adrenal adenoma  bronchial asthma
  • 13. Comorbidities Distribution (n=12) 7 7 5 5 5 4 4 3 3 Hypothyroidism Osteoarthritis Hypertension Hyperhomocystenemia VitD Deficiency Hyperlipidemia Venous Insufficiency Elevated Liver Enzymes IgA Deficiency
  • 14. Comorbidities Distribution (n=12) 2 2 22 2 1 1 Elevated Factor VIII Clotting Cancer/ Tumor Adrenal Insufficiency Fibromyalgia DM-II/ Glucose Intolerance Neuropathy Vit B12 Def
  • 15. Surgical history  gastric sleeve  gastric bypass  removal of excess skin after bariatric surgery – abdomen, thigh lift, arms  hysterectomy  cholecystectomy  total knee replacement  lumbar laminectomy and fusion
  • 16. Laboratory abnormalities  Low vitamin D - usually <15 ng/mL (deficiency)  Elevated CH50 – presence of chronic inflammation  Elevated homocysteine - an amino acid and breakdown product of protein metabolism when present in high concentrations has been linked to an increased risk of heart attacks and strokes  Elevated cholesterol and/or triglycerides  Low HDL, high LDL  Elevated fasting blood glucose, high A1C  Low IgG, IgA – immunodeficiency
  • 17. Laboratory abnormalities  Elevated IgE - allergies  Elevated liver enzymes – fatty liver  Elevated factor VIII clotting activity – risk factor for deep venous thrombosis (blood clots)  Elevated creatinine clearance and low eGFR – kidney insufficiency  Low hemoglobin level, iron deficiency (low total iron and ferritin) - anemia  Low cortisol a.m. level – adrenal insufficiency
  • 18. Lymphoscintigraphy  intradermal or subcutaneous radiotracer injection between toes, fingers  evaluates the lymph flow, obstruction and abnormalities of the lymphatic systems
  • 19. Lymphoscintigraphy  estimates the uptake of a radiolabeled tracer (Tc-99m Sulfur colloid) that is transported into the regional lymph nodes by the lymphatic system  routinely performed as part of evaluation of a swollen limb  this technique might both determine the underlying cause of swelling and indicate its pathophysiology
  • 21. Lymphoscintigraphy findings  tortuous and enlarged lymphatic channels  delay lymphatic flow  lymph pooling, collaterals  none visualization of lymph nodes  enlarged lymph nodes 100% demonstrated lymphatic abnormalities (n=12)
  • 22. Venous duplex lower extremities  venous insufficiency superficial, perforators and/or deep system – common 92% (n=12)  deep venous thrombosis – rarely
  • 23. Abdomen/Pelvis CT scan findings  Fatty liver, enlarged liver  Gallstones  Enlarged pelvic lymph nodes  Aorto-iliac atherosclerosis  Hiatal hernia  Incidental pulmonary nodule  Constipation  Adrenal adenoma  Pancreas fatty atrophy
  • 24. Echocardiogram  Left ventricular hypertrophy  Mild diastolic dysfunction  Trace, mild aortic and mitral valve regurgitation  Dilated left atrium 67% (n=6)
  • 25. Treatment  Manual lymphatic drainage (MLD) / decongestive therapy / application of multilayer compression bandages (foam, short stretch bandages)  Use of compression garments; stockings, arm sleeves, Capri 20 – 30 mmHg; micro massaging garments - better tolerated  Night garments and inelastic compression garments – poorly tolerated  Get proper sleep and exercise
  • 26. Exercise  Low impact aerobic exercises  Underwater exercises  General stretching  Strengthening – progressive resistance – elastic bands, tubing  Studies concluded that slowly progressive exercise of varying modalities is not associated with the development or exacerbation of lymphedema such as aerobic and strengthening  In patients with persistent systemic inflammation as seen in lipedema and lymphedema, regular exercise training lowers levels of pro-inflammatory cytokines
  • 27. Chronic Lymphedema Rockson, S. G. (2013). The Lymphatics and the Inflammatory Response: Lessons Learned from Human Lymphedema. Lymphatic Research and Biology, 11(3), 117-120.
  • 28. Diet Anti-inflammation  high omega 3 – flaxseed oil, salmon, walnuts  green leafy vegetables, celery, beets, broccoli, blueberries, pineapple  avoid allergic/sensitive foods  reduce simple sugars, eggs, dairy, gluten
  • 29. Interventions  Corrections of vitamin deficiencies such as vitamin D, B12, folate, B6  Reduction of homocysteine levels with high doses of vitamin B12, B6 and folate  Replace minerals i.e. zinc, magnesium  Antioxidants & anti-inflammation – curcumin, green tea, resveratrol, vitamin C
  • 30. Selenium  antioxidant properties, trigger immune activation Good source: 1 medium brazilian nut = 95 mcg, 2 nuts a day.  Dose: 200 mcg once a day
  • 31. Bioflavonoids  essential for the proper absorption and utilization of vitamin C  increase the strength of the capillaries, and help to prevent hemorrhages and ruptures, while also building a protective barrier against infection  citrus bioflavonoids, diosmin  Dose: 500mg once to twice a day
  • 32. N-Acetyl-Cysteine  restores intracellular levels of one of the body’s most powerful antioxidant defenses, glutathione Dose: 1.2 g (1) cap twice a day
  • 33. Beta 1,3/1,6 glucans  powerful antioxidant, moderate tissue-damaging cytokines  activation of macrophages, neutrophils, and T-cell– mediated immunity  assist in ameliorating microbial imbalance – fight infections  Foods: cereal β-glucans from oat, barley, wheat and rye; mushroom β-glucans from shiitake mushrooms  Dose: 500mg / day on empty stomach with 8 ounce water
  • 34. Liposuction Water-jet assisted (WAL) and tumescent liposuction  36 y/o female patient underwent WAL for stage I lipedema with good results, later had a thigh lift for loose skin. Lymphoscintigraphy showed slightly prominent lymphatic channels in the ankle joint and distal calves bilaterally right > left, inguinal lymph nodes were identified at 11 minutes; and iliac nodes at the iliac chains visualized bilaterally @ 30 minutes. One year after WAL + diet + exercises lipedema remained under control.
  • 35. Conclusion  Lymphatic abnormalities are evident in early stages  Wide array of comorbidities are present  Multiple treatments and interventions – effectiveness and long-term outcomes are unknown
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