Pathophysiology of Rheumatic Diseases

Sergio Schwartzman, MD: Rheumatic diseases as a whole do not necessarily have a single unifying pathophysiology. If we look at the panel of autoimmune diseases that fit under the rubric of rheumatic illnesses, they are very different. For example, the pathophysiology of gout, which is 1 of the rheumatic diseases, is very different than the pathophysiology of rheumatoid arthritis or psoriatic arthritis.

However, we do know that the immune system is a critical element in the pathophysiology and the clinical expression of these diseases. As we have learned more about the immune system, the pathophysiology is now becoming a little more clear, although for the most part, we still do not know what causes most of the rheumatic diseases.

As a whole, there are a number of tenets that we hold that we believe are critical in the pathophysiology of rheumatic illnesses. I think the first is that there has to be a genetic predisposition. This has been studied in many illnesses, and for some of the diseases that we treat, it is a critical element. For example, in axial spondyloarthritis, or ankylosing spondylitis, the HLA-B27 genomic component is a critical element in the pathophysiology. Most patients who have ankylosing spondylitis are HLA-B27 positive.

However, just having the gene for a disease does not necessary mean that you are going to develop the disease. So, the genetic predisposition is 1 element. The second element is environmental factors. These environmental factors are being increasingly defined, but we still do not know most of them. For example, we know that in rheumatoid arthritis, smoking is an element—an external element—that impacts the correct genetic genome that then results in a rheumatic disease. So external factors, such as smoking, are critical elements in the pathophysiology of rheumatoid arthritis.

Other diseases may have different elements that are exogenous to the genome that are important in the pathophysiology. If, for example, we look at reactive arthritis, the reactive arthritis is usually a consequence of having had some type of infection. In fact, what used to be called Reiter syndrome and is now called reactive arthritis, was first described in people who developed venereal diseases and infection, and then developed an autoimmune system disorder that then resulted in inflammatory arthritis.

Probably the area that has gleaned the most interest now is really a combination of both an external factor but also the genome, and that is the microbiome. These are the organisms that normally live in our bodies. For every 1 human cell that we have, we have 10 foreigners on us. These are generally viruses, bacteria, or fungi. This microbiome is very different in different people, but it has now been characterized in some diseases.

There’s work that has demonstrated that a certain microbiome may be associated with conditions such as rheumatoid arthritis or psoriatic arthritis. However, it is very complex because the only microbiome that we are really focusing on is the gut microbiome, the organisms that normally live in the large bowel. But the microbiome really encompasses our whole body. To attribute a difference in the microbiome of the GI [gastrointestinal] system to a disease process is a little preliminary. How do I know that it’s not the microbiome in my scalp, the organisms that normally live in my scalp, that’s responsible for rheumatoid arthritis or psoriatic arthritis? It’s never been studied.

I think that the microbiome is an area that has implications in terms of the pathophysiology of diseases, perhaps helping us to define them, but ultimately if it is indeed pathologic, and I’m not yet convinced of that, we can modify the microbiome. That is easily done by things such as antibiotics and potentially diets that can modify the microbiome.

Transcript edited for clarity.