Caitlin Whyte (Host): This is Flourish. I'm Caitlin Whyte. And with us today is Dr. Ana Gowani, a rheumatologist from Prisma Health. We're diving into the complexities of living with an autoimmune disease.

Well, Doctor, my first question for you today is how do autoimmune diseases develop and why does the immune system start attacking the body in this way?

Dr. Ana Gowani: So, this is a huge question, and one that doesn't have a simple answer. But what we do know is that there are three known factors that influence the development or pathogenesis of an autoimmune disease. So, that's genetics, the immune system, and then the environment.

A patient's genes can increase the risk or genetic susceptibility for an autoimmune disease. Numerous genes have been shown to increase the risk for developing autoimmune diseases. We know about 80 genes in lupus thus far. However, the individual impact is small. And so, apart from a few very rare autoinflammatory disorders that occur due to defects in one single gene, there's typically not one genetic abnormality at the root of an autoimmune disorder.

And so, the immune system has multiple regulatory mechanisms that help prevent sort of autoreactive lymphocytes from developing. And in autoimmune disease, these regulatory mechanisms break down. So, there's various ways that this can happen. This can be due to defective functioning of antigen-presenting cells like dendritic cells or macrophages or due to a decline in the function or number of regulatory T cells. But again, there are sort of multiple areas in the immune system where these, again, regulatory mechanisms can not work correctly.

So finally, environmental factors are felt to contribute to autoimmune disease. So, tobacco use or cigarette smoking has been linked to an increased risk to rheumatoid arthritis development. And then, other factors like pollutants or exposure to certain viral infections are felt to play a role as well.

Host: So, just why are autoimmune disorders often difficult to diagnose? And what are the most common early warning signs?

Dr. Ana Gowani: So, the challenge is that typically there isn't one laboratory test that can definitively diagnose a patient with a specific autoimmune disorder. So, a test that's commonly ordered by various providers is an ANA or anti-nuclear antibody test, which has a range of patterns and titers or degrees of positivity, and is a non-specific test. And I've had multiple patients come to me saying that they were told that they had lupus because they had a positive ANA, when an ANA actually occurs in about 16% of the general population or almost one in five people. And that number rises to about 30% or almost one in three people when patients are 60 years and older.

And so, just having a positive ANA isn't diagnostic of having an autoimmune disorder. Most autoimmune diseases are diagnosed based on clinical history with presentation of certain clinical features, partnered with specific laboratory studies, including autoantibodies. But it's important to see a rheumatologist for evaluation and diagnosis.

 And there are many presentations of autoimmune disease. So, the early warning signs can vary, but one warning sign that can be seen is the development of new-onset Reynaud's phenomenon in an older individual. So, Reynaud's phenomenon is vasospasm of the digits during which it can look like someone's tied a tourniquet around the middle of your fingers, resulting in severe blanching or pale skin that has a clear demarcation. Then, as if the tourniquet was released, the fingers can become red due to increased blood flow back to the fingers. And so, this is very common in young women. But features of Reynaud's phenomenon that would be concerning for a possible underlying autoimmune disease would be older onset, typically after the age of 30, intense or painful episodes that can even result in ischemic digits or digital ulcers or asymmetric attacks.

Host: Well, you mentioned before that environment and lifestyle come into play a bit when it comes to developing these diseases, but I'd love to also talk about the genetics. What role do genetics have in autoimmune diseases, and why do they affect women more than men?

Dr. Ana Gowani: So, one study recently evaluated electronic health record data from six large medical systems, using a software program that generated an estimated prevalence of autoimmune disease. And so, in that particular study, about 4.6% of the US population had an autoimmune disease. But of those patients, 63% of them were female.

 In this study, women were twice as likely as men to be diagnosed with an autoimmune disease. And for some diseases such as lupus or Sjogren's disease, the ratio of women to men being diagnosed has been reported as high as about 9:1. So, there are many proposed explanations for the difference in prevalence, including hormonal differences, environmental factors, or even the expression of the X chromosome.

 So, it's known that men carry one X chromosome while women carry two X chromosomes. And so, normally in nature, one chromosome in women is inactivated to avoid gene overexpression and overproduction of certain proteins. So, one recent study published in Nature was looking at whether these RNA protein, DNA complexes that are generated to help inactivate that X chromosome, whether or not they play a role in triggering autoimmunity. But at this time, there's still a lot of research being done to help investigate these questions further.

Host: Well, what are some of the biggest misconceptions that patients have about autoimmune disorders?

Dr. Ana Gowani: I think that the term inflammation is used in very generalized terms and can sometimes be misinterpreted. So, people will often come in using the phrase, "I feel inflamed" or "I have inflammation." But a lot of the time, that actually translates into pain or discomfort. And so, there is both inflammatory pain and non-inflammatory pain. And both types of pain can be severe, but it's important to differentiate between the two because the treatment is very different.

Host: Well, that brings us to our next question. How have treatment options such as biologics and personalized medicine changed patient outcomes?

Dr. Ana Gowani: The treatment landscape in rheumatology has changed dramatically over the past few decades. As an analogy, the difference in treatment previously versus now is as if you were using towels to dry up water from a running faucet versus now having the ability to turn the faucet off.

And so, there are many cells that are important in the immune system. But two important players are your B cells and T cells. And so, B cells move through the body to help differentiate between ourselves and proteins that shouldn't be there. They can help detect viruses such as influenza and help produce antibodies to coat the foreign protein. T cells then recognize these antibodies and help eliminate the foreign protein. T cells also can help generate a response to upregulate and produce cytokines, which help produce inflammation to help fight this foreign protein.

And so, in autoimmune disease, the immune system starts to malfunction and instead starts to misidentify your cells as foreign. Biologic therapies have different targets, including cytokines or these small proteins that act as messengers for the immune system that are important for cell signaling and can upregulate inflammatory responses. And so, an example of this would be tocilizumab, which is a biologic medication that specifically targets the cytokine interleukin-6.

 In addition, some biologic agents target specific markers on a cell surface such as CD20, so that they can impact a specific cell population. So an example of This is rituximab, which targets CD20 expressed on B cells and can help deplete B cells. And so, the benefit of biologics is that they're much more precise at targeting the underlying proteins that are causing a ruckus.

Host: And then, beyond medication, I'd love to go back and touch on lifestyle factors again, like diet, sleep, and stress management. Can those influence disease progression at all?

Dr. Ana Gowani: So, one great dietary approach is practicing the Mediterranean diet and avoiding a lot of processed foods. The Mediterranean diet includes a high intake of plant-based foods such as whole grains, fruits and vegetables, nuts, fish, seafood. One study looking at rheumatoid arthritis patients who are following a Mediterranean diet in conjunction with physical activity over three months showed a significant reduction in the disease activity score on 28 joints, or the DAS28, which is a clinical disease activity tool, compared to the control group. And those patients also had an improvement in metabolic outcomes such as body weight, body composition, and blood sugar.

With regards to stress, there have been studies looking at rat models with psoriasis where rats that were exposed to unpredictable stressors for eight weeks had increase in their epidermal thickness and worsened psoriasis compared to controls. Sleep disruptions are associated with poor cognitive function, increased pain sensitivity, and a higher risk for depression. So, it's important to try and optimize as many lifestyle factors as possible to improve health and overall function.

Host: Well, how does living with an autoimmune disease affect your mental health fatigue and just your overall quality of life?

Dr. Ana Gowani: Of patients with autoimmune disease, one study found that more than half can suffer from anxiety and depression. And while the link between autoimmune disease and mental health is not fully understood, you can imagine that some contributors to worsening depression could be a new diagnosis of autoimmune disease, and the implications that may have for a patient's life. Some medications can contribute to fatigue. And then, there are other factors such as pain from a condition that may impact or disrupt sleep, which is also known to contribute to an increased risk for depression.

Host: Also, how can autoimmune patients best advocate for themselves when navigating medical care?

Dr. Ana Gowani: So, one example of advice is that sometimes—so using a disease process example. So, patients with diffuse scleroderma are at higher risk for a complication known as scleroderma renal crisis, which can be life-threatening. This can present with severe hypertension, rapid progressive renal failure, congestive heart failure, or severe anemia.

And so, since scleroderma is rare, not all medical providers are familiar with how to treat what is considered a scleroderma emergency. So for these patients, scleroderma renal crisis prevention card can actually be given to patients with diffuse scleroderma to carry with them in their wallet. This can describe, you know, the warning signs of new-onset scleroderma renal crisis, such as new headaches, blurred vision, abrupt elevations in blood pressure, shortness of breath, et cetera. And it's a card that the patient can give to emergency room physicians to explain what may be happening to them and describes the best treatment course, which is an ACE inhibitor, And so This is just one strategy for a particular group of patients with a rare autoimmune disease designed to help improve health outcomes and help patient's advocate for appropriate treatment early.

Host: And to close it out for us today, Doctor, what advice would you give patients on improving quality of life while living with an autoimmune disorder?

Dr. Ana Gowani: For a lot of my patients, we'll say to just take it one day at a time. A lot of times at the beginning of treatment of an autoimmune disease such as rheumatoid arthritis, there are a lot of moving parts in terms of starting new medications, obtaining screening labs or other tests. I think it's important to try and take it one day at a time. Otherwise, it can become very overwhelming.

 There is a lot in autoimmune disease as well that is out of the patient's control. However, it is also important to try and take control of the factors you can control to help improve your autoimmune disease. For example, working on quitting smoking, trying to follow a healthy Mediterranean-based sort of low processed food diet, taking medications as prescribed; trying to practice good sleep habits at night to promote good sleep, such as reducing screen time; and trying to participate in exercise for at least 30 minutes a day, five times a week.

Host: That was Dr. Ana Gowani. For more information, please go to prismahealth.org/flourish. If you enjoyed this podcast, please share it on your social channels and explore our entire podcast library for more topics of interest. I'm Caitlyn Whyte, and this is Flourish. Thank you for listening.