Back to the Farm

In my gynecology practice, I see a lot of people with thyroid disease, rheumatoid arthritis, celiac disease and scleroderma. Part of that is because I treat people with Lichen Sclerosus of the vulva. People with one autoimmune disease are more likely to develop other autoimmune diseases. Part of it is because women are far more likely to have these problems; 80% of people with autoimmune conditions are female.

The most common question that patients ask when I diagnose them with Lichen Sclerosus is “How did I get this?”. I wave my hands and say something vague about genetics because the true answer is too complicated to explore in a ten-minute office visit.

My first discovery about the complexity of our immune response was in 1998 at the University of Western Ontario where I took a particularly nerdy course on parasites. We learned about an early study funded by the WHO to see which intervention was more effective in preventing tropical parasitic diseases: medication or WASH interventions (water, sanitation and hygiene - toilets, water treatment and handwashing). This type of study is important because parasitic diseases like River Blindness, Elephantiasis, roundworm infection and Guinea worm disease have a huge effect on quality of life for people in tropical countries.

In this early trial they found that both medication and WASH interventions were equally effective in decreasing parasite infection rates. Surprisingly, they also found that allergies and autoimmune disorders become immediately more common on both islands. The “hygiene hypothesis” suggests that with no parasites to fight, the immune system doesn't know when to quit and ends up targeting proteins in the environment and in our bodies. Without the parasite’s special mechanisms to ratchet down the immune response, the reaction keeps causing symptoms, possibly forever.

Turns out that parasites have evolved an almost magical ability to turn down their human host’s immune system enough that it won’t kill them, but not slow it so much that they die of some other infection. The parasite passively and actively changes the balance of almost every immune cell and mediator we make and also secretes anti-inflammatory proteins. The goal of the parasite is to keep us alive so that we can feed them forever. Yum!

We don’t know why the immune system turns on itself and decides to target the thyroid, or the pancreas, or the midline inner skin of the vulva. Sometimes there’s a direct connection to certain infections; for example after bacterial infection with strep, people are more likely to develop psoriasis.

Fifty years of studies have tried to figure out the specifics of hygiene and health. People who live on traditional farms anywhere in the world, or have hunter-gatherer lifestyles have a more diverse bacterial and parasitic microbiome, and also lower incidences of allergies, asthma, and autoimmune diseases. This is called the Old Friends hypothesis, suggesting that our bodies do better when we co-exist with these organisms because we’ve evolved to live together.

The problem is that we can’t figure out exactly how. Some parasites increase the risk of asthma and others decrease them. The immune system is staggeringly complex. Most physicians consider immunologists to be the rocket scientists of the medical hierarchy. Although with Elon Musk being the poster boy for rocket scientists these days maybe I need a new analogy. 

A 2017 study by Varyani et al infected human study participants with the helminth parasites Necator americanus and Trichuris suis and found significant improvements in symptoms associated with Crohn’s disease and ulcerative colitis (both inflammatory bowel diseases). “Helminth therapy” has become a last-resort method of treatment for some people with severe autoimmune diseases. There are people who report dramatic successes in treating ulcerative colitis by swallowing whipworm eggs (T. suis and Trichuris trichiura). I don’t blame them for trying. Ulcerative colitis can be a devastating and painful condition.

The hygiene hypothesis doesn’t completely explain why women are so much more vulnerable to autoimmune disorders. We are much more likely to wash our hands with soap after we use the toilet (65% of women vs 31% of men in a 2009 UK study), and after puberty there is a marked gender difference in gut microbiome. Those differences probably aren’t enough to explain the massive increase in risk for women. 

There is a hypothesis that the number of X chromosomes determines the autoimmune disease risk. People who have 2 X chromosomes have to deactivate one so that they don’t overload the body with X proteins. The RNA that coats the chromosome to turn it off is called Xist and binds proteins that cause strong immune system responses. A 2024 study showed that people with autoimmune diseases had high levels Xist antibodies in their blood. Hopefully, we can use these antibodies to create specific tests for autoimmune disease.

Some people have already heard about the hygiene hypothesis and are worried that kids who grew up during the pandemic in isolation didn’t get all the usual childhood viral illnesses and thus are at increased risk for allergy, asthma and autoimmune diseases.

The part of the immune system that manages viral infection is totally separate from the part that manages bacteria and parasites so the hygiene hypothesis does not apply to viral infections. Viruses may actually increase the risk of certain chronic diseases. HSV, the virus that causes cold sores may be linked to Alzheimer’s disease. Epstein-Barr mononucleosis infection is linked to multiple sclerosis. We optimize our long-term health by being vaccinated.

My family has always spent our summers outside. I bought a tiny home and moved it to the middle of a forest beside a lake. I have fond memories of my kids covered in mud after building shelters from fallen branches or making sandcastles on the beach. I hope I’ve built them a robust microbiome to keep them healthy and happy throughout their lives.