There’s an interesting study by researchers from Texas and Arizona in the US that I would like to discuss this week. The paper is entitled Lymphatic function and anatomy in early stages of lipedema and it was published in Obesity, the research journal for the Obesity Society, in April 2022.
This study had quite an interesting aim. Because it has been shown that several defects in lymphatic anatomy and function are present in the early stages of lymphedema, the authors wanted to see if this was also the case in early-stage lipedema, in other words, before the presence of lymphedema. Specifically, the authors wanted to image the lymphatics of early-stage lipedema using near-infrared fluorescence lymphatic imaging, which uses the agent indocyanine green (ICG).
What were the methods and materials of the study?
20 individuals with Stage I or II lipedema, all of whom had not developed lymphedema, participated in the study. Their average age was 40.5 years and their average BMI was 29.3 kg/m2.
The authors used published data from a group of nine controls (6 men and 3 women) who had an average age of 43 years and an average BMI of 30.3.
Participants had to be 18 years or older with a diagnosis of Stage I or Stage II lipedema in order to be included in this study. Individuals who were allergic to iodine, not willing to travel to Houston for imaging, or pregnant and breastfeeding were excluded from the study.
Each participant received 10-16 injections of ICG to designated locations on their legs, abdomen, and wrists. The authors used the near-infrared imaging of the lymphatics to describe lymphatic anatomy and to calculate “lymph propulsion rates” (how fast the lymph traveled).
What were the results?
Here are the results of the study:
Stage I disease (n=16 legs, 8 participants) had these lymphatic anomalies:
- 3 (19%) had unusually widespread lymphatic vessels
- 4 (25%) had tortuous lymph vessels
- 4 (25%) had radiating lymph vessels (defined as “superficial vessels radiating from the injection site but apparently not connected to deeper lymphatics”)
- 9 (56%) had interstitial backflow (fluid flowing the wrong way and back into the tissue) around at least one injection site
- 9 (56%) evidence of segmentation (meaning that the image of the vessel periodically appeared and disappeared)
- 13 (81%) showed a distinct decrease in brightness of the fluorescent signal in the shins compared to the feet. The authors believe this may be related to how the feet are usually not affected by lipedema, at least in early stages.
- 15 (94%) had dilated vessels
- 0 presented with dermal backflow (or lymph flowing back into the superficial lymph capillaries. This is a typical characteristic of lymphedema.)
Stage II disease (n=22 legs, 11 participants)
- 5 (23%) had either unusually widespread vessels or lymphatic structures with other unusual characteristics
- 8 (36%) had tortuous vessels
- 8 (36%) showed the accumulation of the tracer around at least one injection site (meaning that the tracer was slow to be picked up by the initial lymphatics)
- 11 (50%) presented with evidence of segmentation
- 15 (68%) had radiating vessels
- 18 (82%) showed a distinct decrease in brightness of the fluorescent signal in the shins compared to the feet
- 22 (100%) had dilated vessels
- 0 presented with dermal backflow
Stage III disease (n=2 legs, one participant), all of the above abnormalities were observed in both legs, with the exception of radiating lymphatic vessels and unusually widespread lymphatics. This participant also did not exhibit dermal backflow.
Arms – The arm lymphatics were mostly normal in appearance with the exception of the following:
- 3 arms presented with evidence of segmentation
- 2 arms had tortuous vessels
- 1 had dilated vessels
- One participant, who had previously undergone liposuction of the arms, presented with dermal backflow in both wrists
Note that control data was only available for the lower legs, so arm data was not analyzed for function. The one participant with stage III disease was also not included in this analysis.
The average propulsion rate for lymphatics in both stage I and stage II disease was significantly faster than it was in controls. Both stage I and II lipedema groups had a rate of 1.4, while controls were a mean of .9.
What are the potential limitations of the study?
Two things that could be considered as potential limitations of the study are the small sample size and that it’s not blinded and susceptible to bias.
One example of this potential for bias was in the characterization of some lymph images as “segmented.” Because vessels may appear segmented for a variety of reasons that are completely unrelated to an anatomical or functional problem, the researchers tried to mitigate possible bias by instead reporting it as “signs of segmentation” to better reflect the uncertainty that this was really a problem.
What were the authors’ conclusions?
The authors found some distinct differences between lymphedema and early-stage lipedema. The participants in this study:
- Did not exhibit dermal backflow, which is commonly seen in lymphedema
- Had significantly higher lymph pumping rates than lymphedema
- Had a significant presence of dilated lymph vessels, which are not typically seen in lymphedema patients.
One theory that the authors propose is that because it was found that lipedema and lymphedema both exhibit increased levels of platelet factor 4, a biomarker that is believed to be indicative of lymphatic impairment, it may be that increased PF4 may drive related, but also different, processes of inflammation in lipedema compared to lymphedema.
The authors also believe that the differences between early-stage lipedema and lymphedema suggest that lymphatic failure does not cause lipedema, but may be more of a consequence of lipedema. Certainly, lymphatic failure is very important in the progression to lipolymphedema. The authors propose that the dilation, or widening, of lymphatic vessels and the increased pumping rate, maybe in response to increased inflammation in the fat tissue in lipedema. Once the lymphatics fail to keep up with the increased load in the later stages of lipedema, the reduced clearance of toxins and waste products can further increase inflammation and result in further lymphatic failure. This is a vicious cycle that can contribute to the development of lipolymphedema.
For this reason, the authors recommend appropriate treatment that can successfully interrupt this cycle. They recommend complete decongestive therapy, which is manual lymph drainage, skin care, compression therapy, and movement or exercise, along with a pneumatic pump. (I would add an anti-inflammatory eating plan, such as a ketogenic diet, to this recommendation.)
This study is important for women with lipedema as it offers not so much a potential avenue for early diagnosis of lipedema, but it gives a strategy for ruling out a diagnosis of lymphedema. The usefulness of this paper was also highlighted for me when we received a question recently on one of our social media groups. A person asked if her lymphatics were found to be functioning normally, could she still have lipedema? Because of this paper, I would say that you could still have early-stage lipedema even if you appear to have good lymphatic drainage with lymphangioscintigraphy imaging. Further testing using near-infrared imaging with ICG, as they did in this study, may reveal lymphatic anomalies despite adequate functional performance.
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.