The Scleroderma Chronicles: Coming Full Circle

Systemic Sclerosis is a rare, chronic, progressive, and incurable autoimmune disease that is included in the family of rheumatic conditions. It is characterized by blood vessel damage and the scarring and thickening of skin due to excessive collagen production (fibrosis). The internal organs can also be damaged by inflammation and scarring: the digestive tract, heart, kidneys, and lungs.

There are two main types of systemic sclerosis: diffuse and limited.

I was diagnosed with limited systemic sclerosis 6 years ago.

Hannah: Do you like my circle?

The Circle Starts: In high school I developed a mystery illness that involved intense itching, lots of rashes, sensitivity to sunlight, and swollen digits. I was a mess. It went on for a few years and then the worse of the symptoms faded away.

First Quarter Circle: In my mid twenties I was a researcher working on a scleroderma project for the Division of Rheumatology at the University of Colorado Health Sciences Center in Denver, Colorado. The principal investigator that I worked for was interested in isolating the targets of the autoantibodies that scleroderma patients made; if we found the actual proteins that the antibodies characteristic of this autoimmune rheumatic disease were targeting we would be closer to understanding what they did, and eventually closer to understand the disease process of scleroderma. Let me be clear here: my boss, Dr. Angeline Douvas, was the brains of this little research outfit and I did most of the bench work.

One morning Angie had the hot idea that we should see what happened if we did an anti-nuclear antibody (ANA) test on the polytene chromosomes of the fruit fly Drosophila, a common lab experimental animal. We knew that the antibodies produced by the scleroderma patients were sticking to the chromosomes in the nucleus of cells… what would it look like if we checked this test on the chromosomes of fruit flies which were enormous structures that were easy to look at under the microscope?

After staining we could see that on the entire chromosome a few distinct bands were stained: only a few genes were targeted by the antibodies of the scleroderma patients. What was the function of the genes, and what were those proteins, the clear targets of the antibodies made by these scleroderma patients, doing? Something important that was linked to this disease that we call systemic sclerosis (scleroderma). How was all of that tied to the damaging fibrosis going on in these patients?

Here’s the other interesting conundrum that we kicked around: what changed in these genes/proteins that made them trigger the immune system to make antibodies? There are lots of things that can change genes and the proteins that they make. Things like radiation, chemicals, environmental triggers, viruses…

Hannah: Viruses?! The Kitten Mom and I spend all our time at home hiding from viruses!!!

Second Quarter Circle: Now in my 60s, and diagnosed as a scleroderma patient myself, I began writing letters to my congressman asking him to support the National Commission on Scleroderma and Fibrotic Diseases Act, a bill which would coordinate and organize resources to study the process that is involved in the formation of scar tissue in scleroderma and other diseases/conditions. Two summers ago I met with a representative of my congressman, Jason Crow, with other scleroderma patients to make our case. Scleroderma is special, I argued, because our antibodies are a tool that can be used to unpack the process of fibrosis. Representative Crow did support the bill.

Hannah: Now, are you ready for some really crazy stuff? Hang onto your catnip mice, this gets a little wild!!

Third Quarter Circle: It is 2020 and Covid-19 has arrived. Early on we learned that this is a serious virus that causes an extreme immune system response in some individuals that is life threatening. There is severe lung involvement, blood clots, scarred lungs, injured hearts, failing kidneys… this is no joke if you are already dealing with all of this, so I and other scleroderma patients are avoiding it like the plague and retreating to our online support groups even more than usual. We share observations and experiences in these forums, and it wasn’t very long before we started to notice that these severe Covid-19 cases seemed to be awfully similar to severe systemic sclerosis. We laughed about “Covid Toes” since dealing with blue fingers and toes is a daily struggle for us. Then the news reports about Covid-19 long-haulers started to emerge, and we all started to say to each other… wow… fatigue, brain fog, muscle/joint pains, lung and heart problems… sounds a lot like what we deal with… Then some people started to arrive in our support groups who were newly diagnosed scleroderma patients who were also Covid-19 long haulers. Now every week new people, shocked and frightened by their life-altering diagnosis of systemic sclerosis, are showing up in our forums. “Gee, there are a lot of new patients arriving,” someone wrote last week…

Unbelievable, right? I decided to hunt around online and quickly found that there were a number of reports about Covid-19 and systemic sclerosis. I discovered to my shock that people with severe Covid-19 disease do share a lot of documented clinical features with severely ill diffuse systemic sclerosis patients, and there is a connection between Covid-19 and rheumatic autoimmune diseases. When there was an article in the New York Times reporting that some Covid patients were developing autoimmune disease it caught my eye, so a little more work online found this nicely written overview by the Global Autoimmune Institute that listed specific research reports and the autoantibodies being discovered in Covid-19 patients and Covid-19 long-haulers. There in the reports are listed the same, exact autoantibodies that are the specific hallmarks of my two autoimmune diseases, systemic sclerosis and Sjogren’s Disease. 2020, shame on you. This is really, really bad, even for you.

All of a sudden it is really important to understand fibrotic diseases and how to reverse the damage caused by Covid-19.

Hannah: The Kitten Mom feels like she needs to do something about this!!

The Circle Closes: The genome sequencing service 23andMe has launched a genetic research study of systemic sclerosis patients. They are screening and accepting 1000 diagnosed patients who will donate their DNA for research into systemic sclerosis. I’m pretty sure that this effort to collect more information about the genes of systemic sclerosis patients is in part driven by the urgent need to deal with an emerging flood of new patients with fibrotic organ damage due to Covid-19 infections. Tonight I completed my application to submit my DNA to the study and to participate in all their additional data collection about my disease. Remember those few, distinct genes lit up on the fly chromosome? “Go get ’em, boys!” I muttered to myself as I clicked the submit button.

Today there were 225,558 new cases of Covid-19 in the US and 3,499 new deaths.

How many of the Covid-19 survivors will eventually be dealing with a chronic, progressive, and incurable autoimmune disease?

Wear your masks, people!!

Wednesday Afternoon Update: I’ve been accepted into the research program and they have already shipped my DNA collection kit to me. Hannah is so excited!!

Footnote: Did Angie and I find a protein using the scleroderma patients antibodies? Yep. We did.