Lipedema definition, stages, types, physical findings, co-morbidities, laboratory abnormalities, other tests findings such as Abdomen/Pelvis CT scan, echocardiogram, venous doppler/duplex lower limbs, lymphoscintigraphy; treatment options and therapeutic interventions

1. LIPEDEMA: A FREQUENTLY
MISDIAGNOSED
AND MISUNDERSTOOD FATTY
DEPOSITION SYNDROME
MARGARITA CORREA, MD, CLT
PHYSICAL MEDICINE INSTITUTE
WWW.PHYSMEDI.COM

2. Disclosures
•I have no actual or potential conflict of
interest in relation to this
program/presentation

3. Lipedema
• symmetrical edema in the lower limbs with fatty deposits located on hips and
thighs
• chronic disease that occurs mostly in females with a prevalence of 11% to
18%
• 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

4. Lipedema stages
Fatty accumulation on hips, thighs, legs and arms; feet swelling early on
stage II worsening 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, enlarged subcutaneous tissue
• 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. Lipedema Types
• I: Pelvis, buttocks and hips
• II: Buttocks to knees with fatty folds inner aspect of knees
• III: Buttocks to ankles
• IV: (a-c): Upper arm; lower arm; whole arm
• V: Knees to ankles

7. Chief complaints
• pain mostly on legs
• easy bruising
• leg and arm swelling
• fatty lumps on legs, abdomen and arms
• heaviness on legs
• weakness
• fatigue, tiredness
• swelling and fatty deposition worsening after puberty, pregnancies,
contraceptive pills

8. Pain Score n=52
0
2
4
6
8
10
12
14
16
18
No Pain Mild Moderate Severe
Intensity 18 11 8 15
SCORE
Pain Score

9. Physical Examination
• symmetric fatty deposition on legs, abdomen, arms
• superficial varicosities may be present
• bruises, superficial hematomas
• tenderness to palpation most prominent at pretibial area
• 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

10. Physical Examination
• About 58% of lipedema
patients demonstrates joint
hypermobility
• In adults a Beighton score of
5/9 confirms joint
hypermobility
• Points to a collagen type III
biosynthesis defect

11. Average BMI ≈ 39.17 n=52
1 2 3 4 5 6 7 8 910111213141516171819202122232425262728293031323334353637383940414243444546474849505152
BMI 1 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 6 8
0
10
20
30
40
50
60
70
80
90
BodyMassIndex(BMI)
SUBJECTS
BMI ≥ 25 (obesity)
BMI ≥ 35 with 2 comorbidities-hypertension and DM (morbid obesity)
BMI ≥ 40 (morbid obesity)

12. Staging I-IV n=52
Stage I, 6, 11%
Stage II, 31, 60%
Stage III, 12, 23%
Stage IV, 3, 6%

13. Comorbidities
• high blood pressure
• diabetes mellitus type II, glucose intolerance
• obesity
• arthritis mostly osteoarthritis at spine, hips and knees
• thyroid disease; hypothyroidism, goiter, Hashimoto’s thyroiditis
• metabolic syndrome: cluster of conditions including high blood
pressure, elevated blood glucose, central obesity and
hyperlipidemia
• venous insufficiency
• vitamin D deficiency

14. Comorbidities
• autoimmune disorders – systemic lupus erythematosus (SLE),
rheumatoid arthritis (RA)
• fibromyalgia syndrome
• polycystic ovaries
• irritable bowel syndrome (IBS)
• gluten, lactose intolerance and celiac disease
• breast, cervix malignant neoplasm
• bronchial asthma
• adrenal adenoma

15. Most Common Comorbidities n=52
7
7
10
12
13
15
20
45
Metabolic Syndome
Diabetes Mellitus II
Thyroiditis
Hypothyroidism
Osteoarthritis
Arterial Hypertension
Vit D Deficiency
Venous Insufficiency
0 5 10 15 20 25 30 35 40 45 50
Comorbidities
Incidence
n=45

16. 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

17. Laboratory abnormalities
• Elevated CH50 (total complement) – presence of
chronic inflammation
• Low vitamin D - usually <15 ng/mL (deficiency)
• Elevated C-reactive protein (CRP) - indicator of
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 fasting blood glucose, high A1C

18. Laboratory abnormalities
• Elevated cholesterol and/or triglycerides
• Low HDL (good cholesterol), high LDL (bad
cholesterol)
• Elevated IgE - allergies
• Elevated factor VIII clotting activity – risk factor for
venous thrombosis (blood clots). Predisposing
factors: increased BMI, elevated glucose, high
triglycerides, chronic inflammation

19. Laboratory abnormalities
• Elevated Interleukin-6 (IL-6) - inflammatory condition
• Elevated liver enzymes – fatty infiltration liver
• Elevated creatinine clearance and low eGFR – kidney
insufficiency
• Low hemoglobin level, iron deficiency (low total iron) -
anemia
• High cortisol a.m. level – most common cause in
women is a high circulating concentration of estrogen
resulting in a increased cortisol-binding-globulin

20. Laboratory abnormalities n=52
9
10
12
12
13
14
14
21
34
0 5 10 15 20 25 30 35 40
Factor VIII Act. Clot.
IgE
Cholesterol
IL-6
A1C
Homocysteine
CRP
Low Vit-D
CH-50
Incidence
LabTest

21. Lymphoscintigraphy
• intradermal or subcutaneous radiotracer injection between toes,
fingers
• evaluates the lymph flow, obstruction and abnormalities of the
deep lymphatic systems

22. 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

23. Lymphoscintigraphy
• Normal serial images

24. Lymphoscintigraphy findings
• tortuous and enlarged lymphatic channels
• delay lymphatic flow
• lymph pooling, collaterals
• duplication, triplications
• none visualization of lymph nodes
• enlarged lymph nodes
100% demonstrated lymphatic abnormalities (n=52)

25. Stage I
• tortuous
lymph
channels
• partial
duplication in
left calf
region
• 30’ faint
visualization
of groin
lymph nodes

26. Stage I cont.
• multiple
enlarged
groin
lymph
nodes
bilaterally
• tortuous
lymph
channels
persist

27. Stage II
• Multiple
tortuous
lymph
channels
more
prominent in
left

28. Stage II

29. Stage II cont.
• Partial wash
out of lymph
channels in
calf region
• Enlarged groin
lymph nodes
bilaterally

30. Stage II
• Absent lymph
channels and
lymph nodes
immediately
and 30’

31. Stage II cont.
4 hour delayed image: Faint visualization of
right groin & pelvis lymph nodes and none
seen at the left

32. Stage III
• Tortuous
lymph
channels
with
duplicated
system at
calves
bilaterally

33. Stage III cont.
• Persistent
visualization
of enlarged
lymph
channels

34. Stage III
• Tortuous
lymph
channels at
calf region
bilaterally
with faint
visualization
of groin
lymph nodes

35. Stage III cont.
• Small
lymphocele
in right calf
and
persistent
visualization
of tortuous
lymph
channels

36. Stage III Upper Extremities
Faint
visualization
of axillary
lymph nodes
bilaterally at
60’ (delayed)

37. Stage IV
• Tortuous
lymph
channels in
the right calf
with
visualization
of two
channels and
partial
visualization
of the left
• Faint right
groin lymph
node none
seen on the
left (delayed
flow)

38. Stage IV
• Faint
visualization
of right groin
lymph node
and very
delayed
visualization
of faint left
groin lymph
node at 120’

39. Venous duplex lower extremities
• venous insufficiency superficial, perforators and/or deep system – common
90% (n=45/50). Venous Doppler: 5 normal, 2 not performed
• deep venous thrombosis – rare

40. 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

41. Echocardiogram
• n = 52, not performed = 16, normal = 13, abnormal = 17
• Of the total of echo performed 47% showed left ventricular
hypertrophy, diastolic dysfunction and dilated left atrium as
sign of clinical hypertension; and 17% showed mild mitral
and tricuspid regurgitation, 2% showed mild pulmonary
hypertension.
• All of the test patients (n=36)
had a normal ejection fraction
(LVEF >50%)

42. Treatment
• Manual lymphatic drainage (MLD) / decongestive therapy /
application of multilayer compression bandages (foam,
short stretch bandages)
• Use of compression garments; stockings, arm sleeves,
Capri, leggings 20 – 30 mmHg; micro massaging garments
- better tolerated
• Night garments and inelastic compression garments –
poorly tolerated
• Low pressure intermittent sequential compression device –
well tolerated
• Get proper sleep and exercise

43. Exercise
• Low impact aerobic exercises
• Underwater exercises
• General stretching
• Strengthening – progressive
resistance – elastic bands
• 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.

44. Diet
Anti-inflammation
• high omega 3 – flaxseed oil, extra
virgin olive oil, salmon, walnuts
• green leafy vegetables, celery, beets,
broccoli, blueberries, pineapple
• avoid allergic/sensitive foods
• reduce simple sugars, processed meats
dairy, gluten
• Diet regimens: RAD, Paleo, Ketogenic

45. 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, iron
• Anti-inflammation – curcumin/turmeric, green tea, ginger, garlic,
citrus

46. Selenium
• antioxidant properties, trigger immune activation
• Good source: 1 medium brazilian nut = 95 mcg, 2 nuts a day.
• Dose: 200 mcg once a day

47. 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

48. Micronized Diosmin
• Micronized purified flavonoid fraction (MPFF)
• Promotes lymph drainage, healthy capillary permeability and
favorable microcirculation
• Multicenter, prospective, randomized, controlled studies
document the effect of MPFF on maintaining healthy venous
sufficiency

49. N-Acetyl-Cysteine (NAC)
• restores intracellular levels of one of the body’s most powerful
antioxidant defenses, glutathione
Dose: 1.2 g (1) cap twice a day

50. Vitamin D3
Research now suggests that optimal serum levels of vitamin
D3 support :
• normal cell differentiation
• bone health
• cardiovascular health
• normal immune function
• healthy mood
• healthy glucose metabolism
• normal intestinal immune responses

51. Liposuction
• Tumescent liposuction - Introduces a large volume of tumescent
solution infiltrating the tissues separating the adipose cells from the
connective tissue, later to be aspirated through a cannula.
• Water-assisted liposuction – Introduces a small amount of tumescent
solution and water into the adipose tissue, a modified cannula with a
water jet is inserted into the subcutaneous space, separating the
adipose cells from the tissue, aspirating the solution and detached cells.
Liposuction treatment is an option for patients with a good health
status that have failed all other conservative therapies.

52. Liposuction
Water-jet assisted (WAL) liposuction
• 36 y/o female patient underwent WAL for stage I lipedema
with good results, later about a year after had 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

53. 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

54. 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.
• Reich-Schupke, S., Altmeyer, P., & Stücker, M. (2012). Thick legs - not always lipedema. JDDG: Journal Der
Deutschen Dermatologischen Gesellschaft, 11(3), 225-233.

55. References
• Okhovat, J., & Alavi, A. (2014). Lipedema: A Review of the Literature. The International Journal of Lower Extremity
Wounds, 14(3), 262-267.
• 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.

56. References
• Rockson, S. G. (2013). The Lymphatics and the Inflammatory Response: Lessons Learned from Human
Lymphedema. Lymphatic Research and Biology, 11(3), 117-120
• Szél, E., Kemény, L., Groma, G., & Szolnoky, G. (2014). Pathophysiological dilemmas of lipedema. Medical
Hypotheses, 83(5), 599-606.
• Truchetet F., Bonhomme A. (2015). Recognizing 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.
• Földi, E & Földi, (2005) Das Lipödem. In E Földi & M. Földi (2n Ed.), Lehrbuch del Lymphology: für
Mediziner, Masseure and Physiotherapeuten p444-453.
• Beltran K., Herbst K. L. (2016). Differentiating lipedema and Dercum’s disease. Int. J. Obes. 2005.

57. References
• Juul-Kristensen, B., Schmedling, K., Rombaut, L., Lund, H., & Engelbert, R. H. (2017, March). Measurement
properties of clinical assessment methods for classifying generalized joint hypermobility-A systematic review.
• Narcisi, P., Richards, A. J., Ferguson, S. D., & Pope, F. M. (1994, September). A family with Ehlers-Danlos
syndrome type III/articular hypermobility syndrome has a glycine 637 to serine substitution in type III
collagen.
• Raman M, Milestone AN, Walters JR, et al. Vitamin D and gastrointestinal diseases: inflammatory bowel
disease and colorectal cancer. Therap Adv Gastroenterol. 2011 Jan;4(1):49-62.
• Rapprich, S., Dingler, A., & Podda, M. (2011, January). Liposuction is an effective treatment for lipedema-
results of a study with 25 patients.
• Stutz, J. J., & Krahl, D. (2009, March). Water jet-assisted liposuction for patients with lipoedema: histologic
and immunohistologic analysis of the aspirates of 30 lipoedema patients.