Discussing the Characteristics, Symptoms, Pathophysiology, and Potential Genetic Markers of Lymphedema and Lipedema

By February 24, 2023 No Comments
mechanistic understanding

Today, let’s discuss a review paper entitled Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid , Fat, and Fibrosis, published in the International Journal of Molecular Sciences in June 2022. 

The main objective of this paper was to discuss, compare, and contrast the distinct clinical characteristics, symptoms, pathophysiology, and potential genetic markers of lymphedema and lipedema in the hopes of helping inform future research in this field. 

This paper was a collaboration between researchers in the USA at Texas A&M and Vanderbilt Universities. Two authors that I recognize are Rachelle Crescenzi and Joseph Rutkowski, both of whom have done great research in the past and have really expanded our knowledge regarding lymphatic and fat disorders. 

Clinical Criteria and Symptomatology

The paper first discusses the characteristics and symptoms of lymphedema and lipedema. Interestingly, there is considerable overlap in symptoms but also several very distinct features to these two conditions. 

Both lymphedema and lipedema have stages of progressive severity that include the clinical features of fluid, fat, and fibrosis, but the appearance of these features comes at different times in the course of the two conditions. For instance, increased tissue fluid is prominent in the early stages of lymphedema, while this feature is more prominent in the later stages of lipedema. Likewise, the appearance of fat deposition is seen in the early stages of lipedema but not present until the later stages of lymphedema. 

Lipedema has other distinct features that are either not present at all in lymphedema, such as easy bruising and joint hypermobility, or much less severe, such as chronic pain. Additionally, lymphedema can occur in both males and females and is more likely to appear due to a hereditary cause or treatment for cancer while lipedema occurs almost exclusively in females and seems to coincide with times of hormonal change such as puberty, pregnancy, and menopause.

Molecular Regulators and Pathophysiology

This section discusses the physiology of the disease process in the tissues of lipedema and lymphedema. Most notably, the authors talk about how the pathophysiology of lipedema is so much less understood than that of lymphedema. While there is some understanding of the cascade of events that leads to a presentation of lipedema, we don’t know what the actual trigger is. The triggers are more easily identified in lymphedema. For example, while both conditions end up with a combination of fluid, fat, and fibrosis, the origin of the fluid and fat accumulation in lipedema is very unclear. 

Both lymphedema and lipedema show signs of chronic inflammatory and immune response, but the blood markers that indicate this are much more elevated in lymphedema. The authors suggest several possible inflammatory pathways that may be occurring in lipedema and state further research in this area is needed.  

What is their hypothesis?

One of the very interesting things I learned about in this paper is the hypothesis that although the pathophysiological tissue changes that occur in lymphedema and lipedema are similar, they actually proceed in opposite directions. Lymphedema starts as an excess fluid problem (or edema) that then leads to chronic inflammation and fibrosis, and ends with excess fat accumulation. Lipedema, on the other hand, starts with an excess fat problem that then leads to chronic inflammation and fibrosis, and ends with excess fluid accumulation (or edema).

Genetic Causes or Indicators

Genetic mutations and causes are much more clear for lymphedema, although a confirmed genetic cause can be identified in only one-third of primary lymphedema cases. A great deal of research is currently being conducted as to potential genetic causes of lipedema, but as of yet, genetics has only been used clinically for lipedema to rule out other conditions. 

Further Research Needed

The authors make a Call for Further Research. There is much that is still unknown with regard to both conditions, particularly for lipedema. Here are some of the suggested avenues for research:

  • To what extent is lipedema a lymphatic disease?
  • Or a connective tissue disorder?
  • What causes lipedema-associated pain?
  • Which genetic pathways can cause the characteristics of lipedema?


This paper is important for women with lipedema because it provides a more clear explanation of the symptoms, characteristics, and mechanisms involved in lymphedema and lipedema. The ideas presented for further research may ultimately direct us to more accurately diagnose these conditions and provide more effective treatments. The authors of this review hope that continued research will improve the quality of life for those with lymphedema or lipedema. 

For more updates on the latest research regarding lipedema, check out Lipedema Simplified’s Flash Briefings. It’s our daily mini-podcast where we share tips, tools, and research pertaining to Lipedema.


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