Better Measurement for Better Calcinosis Cutis Treatment

Monique Hinchcliff, MD, MS: I derive all of my research questions from encounters with patients and look to them to help me ask important questions that will, I hope, one day improve their lives.

Although calcinosis cutis affects many different patient populations, including people with sports injuries or advanced kidney disease, it’s particularly prevalent in people with scleroderma. In our cohort of around 500 patients who receive care through the Yale Scleroderma Program, roughly one-third have clinically evident calcinosis cutis. For some of these patients, their calcinosis cutis is debilitating and makes life harder and more painful.

Hinchcliff: Currently, we don’t have any proven treatment options for this condition. There has never even been a clinical trial of any medication to treat calcinosis cutis, so we do not have high-quality data to inform treatment decisions.

Doctors want to help people, so they do prescribe treatments, like calcium channel blockers or high-frequency ultrasound, based on very limited evidence. Some patients seem to feel better with some of these treatments, but outcomes are purely anecdotal. Without a way to measure and quantify, you simply don't know.

Hinchcliff: One major factor is that we don’t have a good way to measure calcinosis cutis. The current approach is for a radiologist to make a few crude measurements to estimate the area and volume of the lesions. On subsequent X-rays or CT scans, they’ll perform the same measurements and give a rough overview to note whether the lesions have gotten bigger or smaller. It’s time-consuming for radiologists, and the information is often too imprecise to be of much use to us.

Without quantitative outcomes, there’s really no way to determine if treatment has made a difference.

Hinchcliff: Our goal was to identify a way to measure calcinosis cutis precisely and then assess if we could detect changes in size using our best guess for effective treatment.

My coauthor, Ian Odell, MD, PhD, and I partnered with Xenophon Papademetris, PhD, in radiology and biomedical imaging, who had previously developed open-source software called BioImage Suite Web. The software includes a tool that allows clinicians to highlight all voxels (3D pixels) in the image where they see calcinosis cutis. When you’re finished, the tool calculates the volume.

We used this new tool in five patients with scleroderma who had symptomatic calcinosis cutis that was causing them pain. After giving them treatment for six months, we repeated the measurements.

The biggest achievement of our study is that we were finally able to accurately measure changes in calcium deposits. It was a very small study, and more work is needed, but we hope this will lead to clinical trials to find an effective treatment for calcinosis cutis based on science.

Hinchcliff: We are working to automate this process by using AI to train the tool to identify calcinosis cutis. In the future, we hope to embed this tool into the radiology technology we use at Yale and elsewhere, so that radiologists can push a button that automatically calculates the volume of the lesion.

We recently received a new National Institutes of Health (NIH) grant to test our tool in more patients with painful calcinosis cutis. This grant builds on previous work supported by the NIH. We will test whether the changes that we see on imaging during treatment are associated with patients’ impressions of change, including their symptoms. It’s not enough to shrink the deposits; we also want to help our patients feel better.