Scarlet Letters, dealing with vascular rosacea, face flushing, burning and the rest: Rosacea and pregnancy hormones (autoimmune disease and microchimerism)

Rosacea and pregnancy
hormones

How does pregnancy affect rosacea? Can pregnancy trigger onset of rosacea? Fetal microchimerism, patient testimonials on pregnancy and rosacea and how to treat rosacea during pregnancy

I've long pondered on this topic. Many years, close to a decade in fact. I have till this day not found a clear definite answer on these questions, but I did find a lot of clues and information. I'll try to put it in this post. Note, I received a comment from a friendly lady who wrote that you shouldn't worry too much about things like pregnancy making rosacea worse, because of the stress it could evoke, and that a lot of things can possibly worsen it, and you should go for it and not let them scare you or hold you back. That it isn't clear how rosacea will respond to pregnancy, so why write about it here? She is right. Rosacea shouldn't come in the way of such important, life changing things as having children. I don't try to scare people, the aim is more to find information that is out there on this topic, to gather it. Patients testimonials both positive and negative, taken from public online forums and websites, although I will point out later here as well that those sailing through pregnancy might not be inclined to post about it as much. So you never get a completely realistic representative idea of the risks, by simply looking at online posts. I try to find explanations why the women who write on public forums that their rosacea worsened, or even have it started during or after pregnancy. Not to say; don't have babies when you have rosacea. My own history in this is complex and multifaceted and not really of a lot of importance in this post, in the sense that in my own choices, it hasn't simply come down to not wanting a redder face. It has been a very long journey in that respect for me, with years in hospitals and all sorts of underlying health problems, but I have tried to keep most of that out of this post and focus on the above topics :)

How does pregnancy affect rosacea?

Rosacea can be affected by pregnancy. Many patients have reported that their rosacea started during or after childbirth. Those at risk for this to happen, might have had a predisposition for rosacea; the genetic make up for it or the risk factors to develop rosacea, like pale (or lighter) skin tone, sensitive skin and being able to blush or get some redness from alcohol, change in temperature for instance. But there are also many testimonials on rosacea forums and in health groups of women who saw their rosacea calm down during pregnancy. How pregnancy can affect preexisting rosacea is a difficult estimation. It has been hard to find clear numbers and research on this topic, but the general consensus is that rosacea can do exactly everything under the sun during pregnancy: either flare, stay stable, or actually be positively influenced by the hormones of pregnancy and by the dampened strength of the immune system during pregnancy. It's tough to predict what will happen to you if you fall pregnant and already have rosacea. My own dermatologist said to me at the time, when I asked and asked and asked about the topic, dying for some doctor to tell me with some certainty "Yes you will be fine, go for it!", that he sees more than half of his female patients doing well, either stable or improving during pregnancy, and less than half of them getting worse. He said when I asked for advice, that he wouldn't advice his patients to refrain from pregnancy, as the rosacea outcome could go either way. And that he felt most of his patients were able to bring rosacea back under control as soon as they could go back on medication after birth or breast feeding. Pregnancy can make rosacea temporarily better he said, possibly because of the rise in estrogen (aka estradiol) hormones, produced by the body. He found estrogen to be, all in all, a positive hormone in terms of suppressing inflammation and flares. On the other hand, the progesterone levels go up too and this can cause a flare up. Not everybody is affected the same by these hormones and for some they have no effect on rosacea. But progesterone has been compared to the 'male' hormone, and can also play a part in acne for instance. After reading up for this blog post, I found some clues that it might not just be progesterone that causes rosacea flares, but that estrogens have a similar potential in fact. This is a little image of the levels of both hormones during pregnancy:

More on these hormones and pregnancy:

In pregnancy and birth, hormones are there to help regulate the many changes taking place to enable your baby to be born safely. Some of the most significant hormones are:

oestrogen
progesterone
oxytocin
endorphins
prolactin

During early pregnancy, the female hormones (which include estrogen and progesterone) have helped release an egg from your ovary and implant it in the lining of your uterus. There are higher levels of both of these hormones during pregnancy as they help to create the necessary increase in blood supply, especially to the uterus and breasts. Progesterone and another hormone, relaxin, also enable the muscles of the uterus to relax to make room for the growing baby. The change may affect other muscles in the body, which can sometimes make your joints and your back ache and affect your pelvic floor. During pregnancy blood vessels will dilate. This can be seen from as early as the 5th week of pregnancy. This vasodilatation can can be induced by neural, hormonal or neurohormonal triggers. Both estrogen and progesterone increase nitric oxide levels in the body, which is a blood vessel dilator (link). Also, the increased volume of blood during pregnancy puts your blood vessels under pressure. Even people with healthy skin can develop spider veins because of this, and for those with an already weakened blood vessels system in the face (which has blood vessels lie closest to the surface, most visible and which has the thinnest skin of your body), the extra blood volume (due to progesterone) can make us looked more flushed and red and hot. The skin will also retain more moisture during pregnancy, which makes it look more smooth and fills up fine lines, giving many a smooth look. Or, if you are unlucky, the puffed up face look from excess water retention and edema :) Many women find that their skin can become more sensitive during the pregnancy. Common skin conditions during pregnancy. There are also other changes brought on by pregnancy which can influence rosacea; in a normal pregnancy, plasma volume, cardiac output and sodium load increase, and systemic vascular resistance falls with a resultant drop in blood pressure of 10 mmHg. To allow tolerance of the fetus, pregnancy produces an environment of immune suppression with depressed immune function of natural killer cells, phagocytic cells and cell mediated cytotoxicity. Malar erythema (see pics), a red rash on the face, is a more common thing to happen during pregnancy and might make it hard to distinguish from a rosacea flare.

The role of estrogen

Estrogen, produced by the ovaries and later by the placenta, helps the uterus grow, maintains the uterine lining steps up blood circulation, and actives and regulates the production of other key hormones. Estrogen increases blood flow to mucous membranes and causes them to swell and soften, giving mom-to-be an endlessly stuffy nose, plus sinus congestion, headaches, and postnasal drip. The flushed pregnant "glow" or skin rashes stem from the same extra blood flow to the skin. Estrogen, along with progesterone and melanocyte-stimulating hormone, can cause skin discolorations (hyperpigmentation), like the darkening of the nipples, areola, and white line that runs down the abdomen. The skin on the forehead, nose, and cheeks may start to look tanned, creating the chloasma, or "mask of pregnancy." Estrogen changes during pregnancy can also cause dilation of the blood vessels, instability and congestion of blood vessels. Also, like progesterone, estrogen affects nitric oxide levels and causes some vasodilatation (source). It is estradiol that stimulation of endothelial nitric oxide synthase. After binding to specific ‘non-genomic’ membrane-bound estrogen receptors, 17β-estradiol has also been found to trigger a nitric oxide-independent vasodilator response, probably mediated by activation of large conductance calcium-dependent potassium channels (source). In the skin, estrogens affect skin thickness, wrinkle formation and skin moisture. Estrogens can increase glycosaminoglycans (GAGs), such as Hyaluronic Acid, to maintain fluid balance and structural integrity. It provides the skin with its ability to resist stretching and keeps the skin firm and moist, giving it the smooth, soft feel we so often associate with the skin of a woman. Androgens, on the other hand, stimulate collagen production resulting in the stronger, coarser skin of a man. Estrogens can also increase collagen production in the skin, where they maintain epidermal thickness and allow skin to remain plump, hydrated and wrinkle-free.

Summarized, estrogen:
-Increases blood flow.
-Affects nitric oxide levels and blood vessel dilation.
-Increases the rate of cell turnover in the basal layer of the epidermis.
-Reduces the size and activity of the sebaceous glands.
-Keeps sebaceous secretion thin and less fatty.
-Slows the rate of hair growth.
-Increases the action of the enzyme hyaluronidase, which produces hyaluronic acid.
-Keeps the skin metabolically active.
-Its regulatory effect on the size and action of the sebaceous gland means that compared with men, women generally have finer pored and drier skins.
Estrogen is not purely a female hormone. It is primarily made in the ovaries and is abundant in females, but it is also found in males and made in different tissues outside of the ovaries. The word estrogen actually encompasses a group of chemically similar hormones, so it is not a single substance. Estrogens include estradiol, the most abundant form in adult females, estriol, the primary estrogen during pregnancy and estrone, which is produced during menopause. In females, estrogens are made by converting the male hormones, known as androgens, into estrogens. And these androgens are initially derived from cholesterol, the primary steroid that gives rise to many steroid hormone families. The conversions from cholesterol to androgens, or from androgens to estrogens, is all made via the actions of certain key enzymes. Without these enzymes, conversion would not be possible. The skin, among its myriad of functions, also has the necessary components to produce both cholesterol – and derive sex steroids from it – within the skin.

The Role Progesterone Plays in Pregnancy and the skin

Progesterone is produced first by the ovaries and then by the placenta starting around the second trimester. Progesterone keeps the placenta functioning properly and the uterine lining healthy and thick, and it stimulates the growth of breast tissue. It smooths muscles and softens cartilage, loosening joints and ligaments, contributing to late-pregnancy aches in the hips and pubic bone. Even your teeth and gums take a beating; gums swell and bleed under the influence of progesterone, which also bathes bad mouth bacteria in a nourishing brew, contributing to "pregnancy gingivitis." Progesterone increases secretions from the sweat glands and can cause acne, or heat rash and pruritic urticarial papules. Progesterone is antiatherogenic, it prevents vasoconstriction by increasing levels of nitric oxide (NO), which causes vasodilation, it inhibits platelet aggregation, it prevents inhibition of the Th1 cytokine response and natural killer cell activity, both of which lead to inflammation. Progesterone causes acute endothelium-independent vasodilatation, probably through the cyclic AMP pathway, in 1st and 2nd order human umbilical arteries and veins and in human omental arteries. In rat tests, administrating progesterone long term caused their cardiac output to be raised and the peripheral vascular resistance to be reduced, resulting in dilated blood vessels. The underlying mechanism of this progesterone-related effect is unclear. (source; here you can read more on other pregnancy hormones playing a role in vasodilatation). The skin contains receptors for progesterone but its action on the skin is unknown. However, it has been shown that progesterone can interfere with the action of estrogen receptors in the skin. Of course, with puberty, menstruation and menopause, progesterone is also a key player. However, the research is still scant in this area. Future research will hopefully shed some light on the interactions between estrogens and progesterone. Progesterone also plays a role in your menstrual cycle (as well as estrogen). Its very individual but for me, progesterone rise means more redness and flushing! In a normal cycle, the first 2 weeks have higher estrogen and low progesterone. Then after ovulation (so around day 14 normally) estrogen decreases and progesterone goes up. especially the few days before your period starts progesterone is high and rosacea flares can be worst for some women. Then once period starts, progesterone drops.

In this interesting article on rosacea skin and aging and inflammation, there is a chapter about hormones:

The relatively high incidence of rosacea among women (some studies indicate that it may be 3 times as common in women as in men) isn't likely to be the result of greater sun exposure, so it's reasonable to look for hormonal causes. In old age, it's well recognized that men's estrogen level rises. But the estrogen industry has convinced women that their estrogen declines as they get older. It's common knowledge that aging rodents often go into "persistent estrus," and that their estrogen levels generally increase with age (Parkening, et al., 1978; Anisimov and Okulov, 1981). Several studies in women have shown that serum estrogen levels rise from the teens into the 40s (Musey, et al., 1987; Wilshire, et al., 1995; Santoro, et al., 1996). Other studies show that serum and tissue estrogen concentrations are not concordant, and that some tissues may contain several times as much estrogen as the serum (Jefcoate, et al., 2001). Local irritation increases tissue estrogen content. The antiestrogens, especially progesterone, begin declining in the 30s, so that the rising estrogen has more effect on the tissues during those years. These are the years in which the incidence of rosacea rises suddenly. Rosacea develops later on average in men, whose estrogen levels rise significantly at later ages. Estrogen's most immediate effect on cells is to alter their oxidative metabolism. It promotes the formation of lactic acid. In the long run, it increases the nutritional requirements for the B vitamins, as well as for other vitamins. It also increases the formation of aminolevulinic acid, a precursor of porphyrin, and increases the risk of excess porphyrin increasing light sensitivity. Both aminolevulinic acid and excess porphyrins are toxic to mitochondria, apart from their photosensitizing actions. Nitric oxide, glutamate, and cortisol all tend to be increased by estrogen. Veins and capillaries are highly sensitive to estrogen, and women are more likely than men to have varicose veins, spider veins, leaky capillaries, and other vascular problems besides rosacea. Estrogen can promote angioneogenesis (new blood vessel formation) by a variety of mechanisms, including nitric oxide (Johnson, et al., 2006). "Estrogens potentiate corticosteroid effects on the skin such as striae, telangiectasiae, and rosacea dermatitis" (Zaun, 1981). Early forms of oral contraceptives, high in estrogen, were found to increase acne rosacea more than three-fold (Prenen & Ledoux-Corbusier, 1971).

Kelli wrote on the rosacea forum about using progesterone supplements during her pregnancy

"When I was pregnant, I was put on progesterone suppositories - twice a day. Man I hated those things, but they more than likely saved my baby's life. So, while I was glad that my baby was viable and healthy (this was after a miscarriage), I was also noticing that the longer I used the progesterone, the worse my face got. I used it for my first trimester, and I looked horrid. I have P&P rosacea, so I broke out horribly! I don't know if it makes a difference that mine were suppositories, and you're speaking of creams, or if it was something all together different. I just know that I was on extremely high doses of the stuff, as well as what my body was trying to produce naturally." Link and link with more information on hormones and your skin. And in this article increased blood flow and vasodilatation in pregnancy is explained.

My German dermatologist was a lot less optimistic about pregnancy prospects for women with rosacea :(

He said that he does see the two different effects, but that there are some clues to predict your own outcome in this. For instance; how bad do the fluctuating hormones in your normal menstrual cycle affect your rosacea? I think many female rosaceans have found that fluctuating hormone levels can reflect in their faces. Many say that the week prior to menstruation can be the toughest, with most flares and outbreaks. That is the same for me. In this last week, estrogen levels are low and progesterone goes up. Here the menstrual cycle and these 2 hormone levels during it are put in a little diagram:

Here a doctor explains the menstrual cycle and changing hormone levels. Some quotes from her site: "Two ovarian hormones are responsible for your menstrual cycles; estrogen and progesterone. [..] Levels of estrogen begin to exponentially rise about a week before ovulation and peak just a day before. This estrogen peak then sensitizes the pituitary and it responds with a surge of LH (luteinizing hormone). LH then causes the follicle to release an egg (ovulation). The “shell” of the follicle now becomes a corpus luteum which now concentrates on producing increasing amounts of progesterone. Circulating progesterone can rise 10 fold during the week following ovulation. Estrogen production also rises about 6 or 7 days after ovulation. Both these hormones cause the glands in the lining of the uterus to become thick and lush so, if an embryo were to be deposited, it could implant, be nourished and grow. If there is no pregnancy to keep the corpus luteum going it succumbs and there is a decline (so sad) of both estrogen and progesterone. These fallen levels can no longer support the lining of the uterus….it sloughs and hence bleeding occurs. The now low level of estrogen stimulates the pituitary to begin to produce FSH and the entire process begins once more.

How do the rise and fall of these hormones affect our skin?

The skin is the largest organ we “own”…. There are hormone receptors in the skin and the blood vessels that supply it. Most of what we know regarding to the effects of estrogen on the skin come form studies of what happens to the skin in the absence of estrogen (during menopause).

Here is the estrogen good stuff:
It increases skin thickness, decreases collagen breakdown, increases collagen production, increases water binding capacity, increases the ability of blood vessels to dilate, increases elasticity and improves wound healing. This hormone helps prevent sebum (lipid) production, which feeds bacteria and increases the development of pimples. Estrogen also effects fat accumulation under the skin (subcutaneous). Here’s an interesting stat: The thickness of subcutaneous fat has been measured during the menstrual cycle, using ultrasound and MRI. The maximum thickness of subcutaneous fat over the thighs and abdomen has been found to increase during the menstrual cycle (as much as 7.3% in the abdominal region and 4.1% in the thighs). This certainly appears to validate your frequently voiced concerns that you are “get fatter” during your period. Whether this is due to an increase in water retention or changes in the fat cells is not clear. There is also estrogen bad stuff that can occur in the skin. It increases pigmentation. It also has been associated with decreases cellular-immune response.

Here is what has been noted during the luteal (progesterone) phase of the menstrual cycle:
There is more sebum production and an increase in skin microbial count….these 2 factors can make you more prone to acne a week before and during your period. The skin is also more sensitive to UVB rays between days 20 and 28 which mean an increase in sun sensitivity.

Effects on the immune system
This is complicated…. estrogens suppress immune response in the cells as well as what we call natural killer activity. (There is a war going on between our bodies and the antigens to which we are exposed). Estrogen also increases certain immune proteins in the blood. Because of this increase in antibodies, estrogen may be the significant factor in our high ratio compared to men (20:1) of developing the autoimmune disorder systemic lupus erythematosis (SLE). And if you remember that T cells help us fight infection….well progesterone seems to suppress their formation. (Note T cell numbers remain depressed throughout pregnancy when there is a huge amount of progesterone produced by the placenta….a possible reason for infection severity in pregnant women.)

The doctor refers to the higher incidence of auto immune diseases in women compared to men. There are a few theories for this, and one is the mentioned different hormone levels in women, but another one is microchimerism (more about that soon).

My German derm. told me a different thing from my London derm; he didn't think pregnancy would treat my rosacea too well. A few of his arguments were; I have flares in the last week of my cycle. I have had an IVF treatment and the pregnancy hormones they administered me caused a pretty bad rosacea flare. I have positive ANA blood levels and a couple of diagnosed auto immune diseases, plus the blood values for lupus. He believes that pregnancy can be a trigger for more lurking auto immune diseases for me, like full blown lupus and arthritis and he thinks it could be the trigger for rosacea going into fourth gear for me. This might be related to a phenomenon called Microchimerism (I will explain this one in a bit). Also, the fact that I had 3 early miscarriages and not one pregnancy made the 6+ week mark is an indication to him that my body is too hostile in a way for it; the immune issues might be too strong to allow a foreign body like a fetus to successfully implant, unless I want to use steroids and other medications to calm the immune system down and help keep the pregnancy. Immunologist says the same thing. Steroids are out of the question for me as they all make my rosacea explode and given all the trouble we had it start with, and the severe impact my rosacea still has on my every day life, we decided against more IVF's at the time (I also have low ovarian reserve). I wrote about it before here, it has been a hard thing to come to terms with and I have a lot less heart ache over it now than 4 years ago when this was at play, but it will probably never be something I'm entirely happy about. If my rosacea was a bit less aggressive and I could just fall pregnant easily and naturally, it would have been easier.

This brings me to the second topic; can pregnancy act as the trigger for the onset to rosacea?

Either because of the hormonal changes, or because of the effects of pregnancy on the immune system? Therefore I would have to rate rosacea as an auto immune disease. This is an assumption, as it is still not clear that rosacea is in fact auto immune in origin, but there are indications that it might be in at least a section of patients. And in my own case an immunologist, internist and rheumatologist have diagnosed other auto immune diseases plus elevated ANA and inflammatory levels, so there is a chance that for me, they are all connected somehow, being all inflammatory diseases affecting the own bodies tissues. And as I wrote before, I do believe that immune related problems, for instance coming the bowel, can be the fire underneath our rosacea. Especially the stories out there of rosacea improving during and after pregnancy make me wonder why that can happen. I read about it on forums and I know 2 girls with rosacea who both had a reduction of rosacea symptoms during pregnancy and all through their breastfeeding year. Both had been very worried of the effects of pregnancy beforehand, as both have the more severe flushing issues, need ventilators, have cold packs at hand. Why does

rosacea get worse according to many and better for some? Perhaps it has to do with the immune system, I wonder. Your immune system response is lowered during pregnancy. The body naturally lowers it down, to prevent the body from rejecting the (of partly foreign dna made) fetus. This means that pregnant women can catch a cold sooner than non pregnant women, but it also accounts for the improvement of some auto immune illnesses during pregnancies (and worsening of others). My friend has severe asthma and had a complete remission during both her pregnancies. Arthritis also tends to improve during pregnancy. I will get deeper into this in the next topic.

Can pregnancy trigger the onset of auto-immune diseases?

It has long been debated, why so many more women develop autoimmune disease than men. In the United States for instance, 75% of the auto immune patients (23,5 million approximately) is female. There are a few autoimmune diseases which men develop equally, or more often than women, for instance type 1 diabetes, Crohn's disease and psoriasis. But the ratio for multiple sclerosis is for instance 3:1 in favor of females, and for systematic lupus erythematosus it is even 9:1. For autoimmune thyroid disease the ratio is 8:1. The reason for this disproportionate division is still not entirely clear, but has been researched a lot. Something that is different in men and women, is that women have higher numbers of CD4 cells than men (CD4 are white blood cells connected to T helper cells; they send signals to other types of immune cells, the CD8 or killer cells for instance, which then destroy the infection or invading threat), and an increased CD4/CD8 ratio, plus higher levels of IgM (a type of antibody that is produced by B cells and which is one of the first antibodies which attacks an antigen) and Th1 cytokine production (cytokines are hormonal messengers who play a big role in the immune system, immunity and allergic responses; some are pro-inflammatory and some are anti-inflammatory but promoting allergic responses). So all these ones are linked to immune function and attacking invading threats in the body. You can imagine that having too high numbers of them could make the immune system more likely go in overdrive. It is thought that triggering the immune system can lead to the onset of autoimmune diseases (although genetic predisposition is also at play). These triggers can be hormonal changes, explaining why many female patients find that their symptoms and inflammatory outbreaks follow waves of intensity during their menstrual cycle and pregnancy or when they use the pill. "In a number of experimental disease models estrogens exacerbated disease, and androgens can inhibit disease activity. However, human studies have failed to demonstrate a clear-cut influence of hormonal environment on disease susceptibility to lupus or other autoimmune disorders." More on that can be read here. Also, there are autoimmune diseases which start in childhood, when these hormonal differences are not really as much at play yet, for instance juvenile rheumatoid arthritis, and even then more girls than boys develop it. The different sex hormones are however not thought to be the holy grail in explaining this phenomenon of women having higher onset of autoimmune disease (AID). Many AID occur after reproductive years and giving people extra sex steroids isn't usually having disease altering effects.

Another theory for this phenomenon is X chromosome inactivation, where one of the two X chromosomes which women carry is inactivated in favor of the other, leading to potential susceptibility to autoimmune disease. It is still a theory and quite complex matter for me to understand as a non doctor, but it is linked to reduced T cell (or B cell) tolerance. Lowered T cell tolerance is critical in all forms of autoimmune disease. It makes that the body no longer tolerates the own cells and self-antigens. Self antigens are any of your bodies own antigens (for instance mitochondria, muscle, parietal cells) which set up the production of autoantibodies, needed to defend the body from infection and harm. We need them to be fine tuned; only attack the invading bacteria and viruses, not our own body cells. But this goes wrong in autoimmune disease and we find our immune system attacking the own organs for instance, thinking it is an invader. However, it was also long clear that pregnancy is linked to autoimmune disease onset. It causes an increased risk to develop them.

Can pregnancy trigger post-pregnancy fetal microchimerism?

Fetal microchimerism refers to the presence of low concentrations of two genetically different cell populations in one person's body. It can take place after blood transfusion, organ transplant, from being twins in the uterus and sharing the same placenta, but also from pregnancy itself. Fetal microchimerism refers to the presence of low levels of fetal cells who persist in maternal tissues during and after pregnancy; so cells from a fetus or baby that has been growing in the mothers body can somehow, through the placenta, nestle itself in the body of mum. And because the babies cells are only for 50% made out of the mothers DNA, and for the other 50% from the fathers DNA, this 50% strange DNA can sometimes cause immune problems in the mother, as our own immune system does not like foreign cells in the body. I'll go further into this. The connection between fetal microchimerism and human disease was first made by J.L. Nelson, who thought that it could explain the higher incidence of autoimmune disease in women. When a woman is pregnant, the child is fed through the placenta. Cells pass from the mother to the child and vice versa. Scientists discovered that there are also little cells from the fetus/baby going back into the blood stream and body of the mother who stay there. During pregnancy, this happens in a symbiotic way, and the lowered immune response in the mother due to the pregnancy hormones makes this all possible. However, these fetal cells are not only in the mothers system during pregnancy alone. The discovered already back in 1979 the presence of calls with Y chromosomes in a woman's body. Since women have only 2 X chromosomes (and men X + Y chromosome), scientists concluded that these cells must come from the son she had. Since it has been discovered that all pregnant women carry such fetal cells in their body, up to 6 percent of the free floating DNA in her blood consists of cells from the child. This percentage goes down after birth, but now it has become clear that a smaller percentage of cells stays in the mothers body, for up to 30 years. They are stored in organs, bone, skin for instance. The theory is that this is an evolutionary helper; when a mother has a second baby from the same partner, her body and immune system will detect the same DNA combination as what is already stored in her

body, and the chances of miscarriage will go down. They now suspect that these fetal cells, which consist for 50% of the mothers own genes and for 50% of the dad's, making it a partly foreign body, can also kick the immune system into defense mode. Likely only for those women with a comprised immune system and a predisposition for auto-immune disease, but even that isn't fully understood yet. The mechanism would then be that the body wants to detect and eradicate these 'invading' foreign cells, but since they are safely and long term stored in the mothers body tissues, they cannot be killed and in term the immune system can run wild with forming inflammatory substances to attack, aiming it instead on a certain organ for instance. Which is what effectively happens when you have an autoimmune disease. And scientists found recently fetal cells from decades earlier in tissues and organs of women with autoimmune diseases. They also link this microchimerism to risk of cancer (reduced risk of breast cancer), rheumatoid arthritis and other autoimmune diseases (both increased risk), and since the fetal cells stay decades after giving birth in the mothers body, so is the increased risk of developing these autoimmune diseases. However, the link has not been proven without a doubt yet, it is a research in the process. But information is very diverse on this topic and in this big scale scientific research I read:

"It is accepted that even short-term microchimerism can lead to autoimmune disease and the higher amount of trafficking at caesarean section might increase the exposure of these mothers and facilitate the development of autoimmune disease."

It would seem a better explanation in a way than X chromosome inactivation, because the onset of autoimmune disease in men and women tends to follow a similar path and similar numbers, right up to the reproductive years of women; after approximately age 20, women get a massive rise in autoimmune disease, while the statistics for men stay on roughly the same level. Only after menopause do these percentages get back on the same line.

How soon in the pregnancy does microchimerism take place?
To develop microchimerism, it is not necessary to go through the full pregnancy and to deliver a baby. It starts to take place very early on in the pregnancy, from 6 weeks gestation. Also, scientists found that the highest levels of fetal cells ( up to 500,000 nucleated fetal cells) were found back in the mothers circulation after an abortion had taken place. Possibly because there is a cutting off the placenta then and more fetal cells can enter the uterus and mothers body therefore freely. Fetal microchimerism is measured by using a technique called polymerase chain reaction (PCR), where Y chromosome DNA is identified. Microchimerism takes place regardless of the babies sex, but since mother and daughter both carry two X chromosomes, it is much easier to detect microchimerism through the one Y chromosome of a son. Here is an image of the research outcome, where they tested if types of pregnancy outcome influenced the onset of autoimmune disease:

Their final conclusion was:
"In this study we report the risk of autoimmune disease during and after pregnancy. Overall the risk of autoimmune disease (AID) in women was significantly higher in the first year following vaginal delivery or caesarean section, but was lower in the first year following abortion. While the risk of AID was reduced between the 3rd and 10th year following vaginal delivery, there was no evidence of a change in the risk of AID beyond the first year following CS or abortion. However, women who were pregnant had a higher incidence of AID than those who had no pregnancy records. Pregnancy has both short and long term effects on the woman's immune system. Fetal microchimerism, or low levels of fetal cells persisting in the mother, is implicated in the pathogenesis of autoimmune diseases, which have a predilection for women after childbearing. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. To our knowledge, this is the first epidemiological study on the risk of AID following pregnancy. The main strength of the paper is the large cohort used and the fact

that it is population based, which avoids the problem of selection bias." So to summarize, levels of microchi-merism were measured in women having abortions compared to deliveries of their babies, both natural births and caesarean sections. They were connected to how many of these women developed autoimmune disease (AID). Women who had a vaginal delivery or caesarean had the highest risk of developing AID (caesarean the highest risk of the two). Scientists think it has to do with the amount of fetal cells that getting in contact with the mother during these incidents. These researchers found however that women who had an early abortion, had less risk of developing AID, and they think that the fetal cells that are interchanged then are very primitive fetal cells, which might somehow have a protective effect against AID on the mother receiving them. But overall, women who had been pregnant had a statistically higher risk of getting auto-immune diseases than women who had never been pregnant.

In this scientific rapport
scientists researched and compared the levels of fetal microchimerism (FM) resulting from miscarriage or abortion. They found that FM levels were higher after an abortion than after a spontaneous miscarriage. Abortions that were done surgically also resulted in higher FM cell count in the mother compared to medically induced abortions (with abortion inducing drugs). FM is also later detectable when it is the result of miscarriage/abortion, than when it stems from a full term pregnancy; years later in fact. And fetal cells (from the baby) that are stored in the mothers body for years or decades after the pregnancy, can be linked in some cases to auto-immune diseases. Some cases of rosacea are also thought to be auto-immune related. "We found that fetal cell transfer was common in both miscarriage and abortion. [..] Additionally, aneuploid or otherwise genetically abnormal fetal cells are overrepresented in miscarriage and pregnancy termination compared with uncomplicated term deliveries, and the implications of acquiring genetically abnormal cells are unknown."

	Pre-treatment	Post-treatment (30 min)	Post-treatment (2 weeks)
Fetal microchimerism detection, n (%)	4/75 (5%)	18/75 (24%)	2/5 (40%)
Fetal microchimerism concentration,* median (range), mean	0 (0.0–0.7), 0.1	0 (0.0–36.0), 10.6	0 (0.0–0.7), 0.2

Table 1. Fetal microchimerism detection and concentration after miscarriage and pregnancy termination

The researchers state that because there are so many missed miscarriages (close to half of all pregnancies), and because of the risks FM pose on health onset, this could pose a problem for general womens health. "Women who have given birth to a child with Down Syndrome for instance, have a higher risk of developing Alzheimer dementia (a common risk in individuals with Down Syndrome themselves). Whether this could be related to microchimerism from the child with Down Syndrome is unknown, but it is notable that both murine and human studies have demonstrated localization of microchimeric cells in the brain of the mother." It is clear that pregnancy loss (miscarriage or pregnancy termination) can result in acquisition of cellular fetal microchimerism that can persist long-term. Further investigation of the relationship between pregnancy outcomes and both immediate transfer and long-term persistence of fetal microchimerism is needed in order to better understand reproductive influences on disease. Fetal microchimerism has been associated with both beneficial and detrimental effects. Furthering our understanding of the physiology of maternal-fetal cell transfer and the ways in which obstetric management can influence the process may allow us to shift this balance toward benefit. This is a very easy to read and interesting article on fetal microchimerism and the positive and negative health effects it can have for the mother. And this and this easy to follow article does the same. FM can help protect against the onset of breast cancer, multiple sclerosis and rheumatoid arthritis (These conditions improve during pregnancy and for some time afterward — suggesting that the mother’s immune system is more focused on attacking the “other,” not herself), but increase the risk of developing other autoimmune diseases like lupus. "While fetal cells may stimulate the mother’s immune system to be more vigilant, this dynamic can tip into something like violence. A mother’s body may attack the fetal cells within, and in the crossfire her healthy cells get bombarded. The fetal cells themselves may also attack us, the little traitors. What sets off these battles is unknown, but in the fallout, we may suffer autoimmune diseases like scleroderma and lupus". Fetal cells can also act as cancer stem cells in the mothers body. It is unclear if FM can have any effect on rosacea. Rosacea isn't even classed as a strict autoimmune diseases yet, although it seems clear that at least a portion of rosasea sufferers have underlying autoimmune diseases and quite possibly have rosacea acting like an autoimmune diseases, with the body promoting inflammation in the skin and bloodvessels.

And on a different note, there are also cells of the mother circulating in the body of the baby, both while it is in the uterus and once it is born. Nearly 1 in every 100 cells in a fetus comes from her mom. The population plummets to something like 1 in 100,000 after birth, but they still are present then and breast feeding will make more cells enter the babies body again. "Maternal cells are busybodies. Some researchers think they train and shape the baby’s immune system and even decrease the risk of allergies. They’re healers too; there’s evidence that maternal stem cells can morph into, for instance, insulin-producing cells that proliferate and repair damaged tissue in kids with juvenile diabetes. And, like fetal cells in mothers, maternal cells in children may cause autoimmune problems. How many people have left their DNA in us? Any baby we’ve ever conceived, even ones we’ve miscarried unknowingly. Sons leave their Y chromosome genes in their mothers. The fetal cells from each pregnancy, flowing in a mother’s bloodstream, can be passed on to her successive kids. If we have an older sibling, that older sibling’s cells may be in us. The baby in a large family may harbor the genes of many brothers and sisters. My mother’s cells are in my body, and so are my daughter’s cells, and half my daughter’s DNA comes from her dad. Some of those cells may be in my brain. This is squirm-worthy. But there’s something beautiful about this too. Long post postpartum, we mothers continue to carry our children, at least in a sense. Our babies become part of us, just as we are a part of them. The barriers have broken down; the lines are no longer fixed. Moms must be many in one." It is interesting that during testing, one firth of women without a son were tested positive for FM. This can be explained by (missed) miscarriages of a male embryo, a vanished male twin, or even male cell transfer from an older sibling through the maternal circulation to a later pregnancy. There has even been done a suggestion that intercourse could lead the way to male DNA entering and staying in the body, but this has not been researched yet.

So, it sounds like there’s some mixed effect going on here. Fetal cells can sometimes cause auto-immune disorders (like scleroderma and lupus), but they might also be protective in some cases (like rheumatoid arthritis and multiple sclerosis), depending on factors we don’t understand very well yet. See this research article for more in depth info on this. My risk investigation towards rosacea is that its closest linked to LUPUS, one of the 4 autoimmune diseases mentioned in these articles to worsen due to fetal microchimerism, and therefore pregnancy can in theory exacerbate rosacea along the same pathways, possibly. Apart from the hormonal imbalance and the increase of hormones like estrogens and progesterone, aiding in rosacea-like symptoms, perhaps microchimerism can be another piece of the puzzle in trying to find out why exactly pregnancy can sometimes make rosacea worse for (some) patients.