Lipedema is a disease of fibrotic loose connective (adipose) tissue on the lower abdomen, hips, buttocks, legs and arms of females, sparing the head, trunk, hands, and feet. Lipedema is rare in men.  Inflammation has been found within lipedema tissue^{1, 2} resulting in tissue fibrosis and pain.  As lipedema advances, there may be nerve damage causing the painful tissue to now become numb.³

Lipedema was first described in 1940 by both Allen and Hines at Mayo Clinic in the US⁴ and by Moncorps from Germany⁵  Despite the passage of over 80 years since it was first described, lipedema still remains under-recognized.  It may have become acceptable that this fat is a usual hereditary component in families where it is expected all the girls in the family will have large thighs or a bigger derrier.⁶ 

Lipedema is often confused with non-lipedema obesity or lymphedema due to increased leg size.⁷

Etiology of Lipedema

The etiology of lipedema remains unknown currently.  However, a trigger for the development of lipedema tissue may be an increase in fluid and connective tissue remodeling that occurs alongside body changes during puberty, childbirth, menopause, stress associated with lifestyle change, or by altering tissue structure after surgery or trauma.¹⁰  Over half of women with lipedema have hypermobile joints.¹¹   Hypermobile joints are part of a connective tissue disease including generalized hypermobile joints or hypermobile Ehlers Danlos syndrome (hEDS) could contribute to the development of lipedema tissue by weakening elasticity in skin and fat and weakening walls of the blood vessels allowing more fluid to enter tissue.  As excess fluid enters tissue, it binds to proteoglycans (protein backbone to which complex sugar molecules [glycosaminoglycans] are bound) which is a way for the body to protect itself against excess fluid in tissue.  If too much fluid sits in the tissue, cells essentially drown and die causing more inflammation and fibrosis to form. 

A gene has been identified for a family with lipedema.  A mutation in the gene, AKR1C1, reducing aldo-keto reductase activity, should increase levels of progesterone which can cause fat to grow.  This mutation would also decreasing  prostaglandin F2α levels which can also cause fat to grow.  Finally, this mutation would raise levels of the potent analgesic, allopregnanolone which could reduce pain.^{12, 13}  Therefore we think that pain is not a requirement for the diagnosis of lipedema.

Identifying Lipedema

Lipedema is identified by clinical exam¹⁴ with diagnostic criteria to help guide the clinical diagnosis.

Diagnostic Criteria for Lipedema

1. Most often occurring in women

2. Tenderness of the tissue to touch, though not always

3. Nodules in the tissue the size of rice grains, pearls or larger

4. Disproportion between smaller trunk and larger legs and/or arms

5. Difficulty to lose lipedema tissue after diet, exercise or bariatric surgery

6. Easy bruising

7. Hypermobile joints (hypermobile Ehlers Danlos Syndrome) in about 50%

8. Vein disease (varicose veins or chronic venous insufficiency) not uncommon

9. Family history of lipedema or larger lower body

Under-recognition or misdiagnosis can delay identification of lipedema for years or even decades.⁶ 

Stage and Location (Type) of Lipedema Tissue

Skin and lipedema LCT are graded by stage and location.  Lipedema tissue, body mass index (BMI), metabolic disease and lymphedema increase with stage.^{3, 11}

Stages of Lipedema

Stage 1: Skin is smooth but small nodules are present underneath the skin.

Stage 2: Indentations in the skin with larger masses and fibrosis in the tissue

Stage 3: Larger masses and lobules of skin and tissue.

Lymphedema can occur at any stage but is more often in Stage 3.

Lymphedema can occur at any stage but is more often in Stage 3.

Types of Lipedema

The types of lipedema do not adequately describe the locations of lipedema on the body. 

Types of Lipedema (where affected tissue is located)

1. Under umbilicus and over hips and buttocks

2. Under umbilicus and down to the knees

3. Under umbilicus and down to the ankle

4. Arms

5. Lower legs (rare)

Treatments for lipedema

Patient access to appropriate and timely treatment is often diminished⁸ and patients frequently find themselves blamed for their condition, including self-blame.⁹  Lipedema can be treated to reduce pain and edema, maintain mobility, and improve quality of life while slowing disease progression, therefore timely diagnosis is important.

There are many treatments for lipedema.  The following table includes some of them.

You can read more here: https://www.ncbi.nlm.nih.gov/sites/books/NBK552156/

References

1. Felmerer G, Stylianaki A, Hägerling R, et al. Adipose Tissue Hypertrophy, An Aberrant Biochemical Profile and Distinct Gene Expression in Lipedema. J Surg Res 2020; 253:294-303.: 10.1016/j.jss.2020.1003.1055.

2. AL-Ghadban S, Cromer W, Allen M, et al. Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue. Journal of Obesity 2019.

3. Herbst K, Mirkovskaya L, Bharhagava A, et al. Lipedema Fat and Signs and Symptoms of Illness, Increase with Advancing Stage. Archives of Medicine 2015; 7: 1-8.

4. Allen EV and Hines EAJ. Lipedema of the legs: A syndrome characterised by fat legs and orthostatic edema. Proc Staff Meet Mayo Clin 1940; 15: 184-187.

5. Moncorps C BG, Herteld F et al. xperimentelle untersuchungen zur frage akrozyanotischer zustandsbilder. Arch Derm Syph 1940; 186: 209-215.

6. Todd M. Lipoedema: presentation and management. Br J Community Nurs 2010; 15: S10-16. doi: 10.12968/bjcn.12010.12915.Sup12963.47363.

7. Buso G, Depairon M, Tomson D, et al. Lipedema: A Call to Action! Obesity (Silver Spring) 2019; 27: 1567-1576. doi: 1510.1002/oby.22597. Review.

8. Shavit E, Wollina U and Alavi A. Lipoedema is not lymphoedema: A review of current literature. Int Wound J 2018; 15: 921-928. doi: 910.1111/iwj.12949. Epub 12018 Jun 12929.

9. Fetzer A and Wise C. Living with lipoedema: reviewing different self-management techniques. Br J Community Nurs 2015; 2015 Oct;Suppl Chronic: S14. Review.

10. Buck DW, 2nd and Herbst KL. Lipedema: A Relatively Common Disease with Extremely Common Misconceptions. Plast Reconstr Surg Glob Open 2016; 4: e1043. eCollection 2016 Sep.

11. Torre YS, Wadeea R, Rosas V, et al. Lipedema: friend and foe. Horm Mol Biol Clin Investig 2018; 33(1). /j/hmbci.ahead-of-print/hmbci-2017-0076/hmbci-2017-0076.xml. doi: 2010.1515/hmbci-2017-0076.

12. Nair AS and Diwan S. Allopregnanolone: A neurosteroid for managing acute and chronic pain conditions. Saudi J Anaesth 2019; 13: 264-266. Journal Article 2019/07/25 06:00.

13. Michelini S, Chiurazzi P, Marino V, et al. Aldo-Keto Reductase 1C1 (AKR1C1) as the First Mutated Gene in a Family with Nonsyndromic Primary Lipedema. International Journal of Molecular Sciences 2020; 21: 6264. DOI: 10.3390/ijms21176264.

14. Herbst KL. Subcutaneous Adipose Tissue Diseases: Dercum Disease, Lipedema, Familial Multiple Lipomatosis and Madelung Disease. In: Purnell J and Perreault L (eds) Endotext. Massachusetts: MDText.com, 2019.