Xanthelasma

People may be affected by a fatty deposition in the eyelids. The effect is more easily seen in people who have elevated levels of cholesterol and is therefor sometimes used as a marker of hyperlipidemia.

But I’m not interested in hyperlipidemia although I keep it in mind that lipid deposition is part of the pathology.

My interest is more in finding out what causes it and therefor I went in and try to understand it a bit better in the hope that it may reveal something useful for those who are affected.

Histiocytes

Different sources tell me xanthelasma is caused by histiocytes which develop into a foamy cell. Foamy due to how they look under a microscope.

Xanthelasma (pronounced “zan-the-las-ma”) is a non-cancerous growth made up of immune cells called histiocytes. Histiocytes are specialized cells that help remove waste products from the body. The histiocytes in a xanthelasma look much larger than normal histiocytes because they are full of lipids (fat). Xanthelasmas appear as small, yellow bumps on the upper, and sometimes lower, eyelids. Xanthelasma is a type of xanthoma.

source: https://www.mypathologyreport.ca/xanthelasma/

That is as far as most sites go but this is already quite good. It makes it worthwhile to check out what histiocytes are and why they collect these lipids, presumably LDL cholesterol.

Histiocytes are differentiated monocytes which ultimately come from the bone marrow. Monocytes can also differentiate into macrophages which is interesting as those also can form foam cells as noted in atherosclerosis. So naturally there is a concern that xanthelasma is somewhat predicting CVD.

Histiocytes can further evolve into Langerhans cells which are tissue resident macrophages so you can see they are very closely related.

Here I have broaden a bit the search to see what happens to histiocytes at various locations, not just on the eyelids. Just to see if there is a general tendency to form foamy cells or if that is isolated to the eyelids.

There is surprisingly little literature available. One property of these types of cells is that they exert phagocytosis to take up debris and bacteria. So I looked for the combination of foam cell feature and detection of bacteria. Below are several of the results.

1st case, A bone marrow sample showed that the histiocytes contained the bacteria Brucella Melitensis. A 6-week antibiotics cure for this gram-negative bacteria resolved without recurrence.

https://jamanetwork.com/journals/jamapediatrics/fullarticle/348928

2nd case, A severe case of necrotizing Escherichia coli skin infection marked with foamy histiocytes and gram-negative staining for cocci and rods.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8102677/

3rd case, An other rare infection case but in this case caused by the Actinomyces bacteria. This time there are no foamy histiocytes but there are foamy macrophages. However this is done under a microscope so it is not done through staining.

https://sites.kowsarpub.com/apid/articles/13049.html

4th, Leprosy is caused by the gram-positive Mycobacterium leprae bacteria.

https://dermnetnz.org/topics/leprosy-pathology

5th case, tuberculosis caused by Mycobacterium tuberculosis marked by foamy macrophages.

These cells are filled with droplets of lipids, a well-known nutrient for persistent bacilli. We found that within these cells, the bacilli do not replicate, but remain alive and seem to internalize host lipids. The foamy macrophages might thus constitute a reservoir for persisting bacilli within their human host, and could provide a relevant model for screening of new antimicrobials against non-replicating persistent mycobacteria.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2575403/

6th case, a rare bacteria Stenotrophomonas maltophilia septicemia marked by cutaneous foamy macrophages.

https://pubmed.ncbi.nlm.nih.gov/33034921/

Several cases and some more literature tell me that first of all the distinction between histiocytes and macrophages is very vague and not always determined. Secondly, apart from other possible causes, both histiocytes and macrophages engulf bacteria but do not always seem to get rid of them. Instead, these bacteria succeed in surviving inside the cell so that the foamy histiocyte persists. It is proposed in the link on tuberculosis that the bacteria even drive the uptake of lipids by the cell.

If bacteria sort of direct the host cell to take up lipids then higher circulating lipids may help in succeeding. I suspect the bacteria enforce this through how they affect metabolism of the host cell.

Advice

The conclusion is not bullet proof but it shows us a first hint of what could be going on.

1) There is a chance that you developed Xanthelasma due to an ongoing bacterial infection. You could discuss this with your doctor/dermatologist and ask for a biopsy to test for bacteria. If the bacteria can be identified then they can prescribe the most effective antibiotic for it and hopefully that will resolve the issue.

It is important to match the right antibiotics. There are broad purpose antibiotics available but that could be a hit or complete miss.

2) As an alternative you could try sunbathing, exposing the affected area to direct sunlight. Naturally don’t overdo it from the start as you’ll easily burn your eyelids. By inducing vitamin D production in the affected areas, you give the cells the chance to produce its own antibiotics. This is especially true for skin cells.

Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses.

source: “The Essential Role of Vitamin D in the Biosynthesis of Endogenous Antimicrobial Peptides May Explain Why Deficiency Increases Mortality Risk in COVID-19 Infections” https://www.preprints.org/manuscript/202005.0265/v1

“The Human β-Defensins (-1, -2, -3, -4) and Cathelicidin LL-37 Induce IL-18 Secretion through p38 and ERK MAPK Activation in Primary Human Keratinocytes” https://www.jimmunol.org/content/175/3/1776

A warning though, these lysozymes are not effective against all bacteria. But it is a cheap convenient treatment if you live in an area blessed with sufficient sun. Perhaps also something worth talking to your dermatologist about. They can offer a treatment with UV light that may stimulate the same vitamin D production.

And another warning, if you plan to do something about it surgically then keep in mind they advise to stay out of sunlight so be sure to discuss this with your doctor.

Good luck, I hope this is able to help you out.

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