Doctors often describe sarcoidosis as a diagnosis of exclusion.
“There’s a typical configuration of inflammatory cells present in a granuloma. You must prove that there is not an active infection or cancer,” explains Lynn Hassman, MD, PhD, assistant professor of ophthalmology at the University of Colorado School of Medicine. “Once you’ve excluded those diseases, you’re left with sarcoidosis. But the one disease we call sarcoidosis can affect patients in very different ways.”
Doctors and researchers know more about what the condition isn’t than what it is. Hassman says it’s likely that sarcoidosis is actually several diseases that could be defined differently depending on the part of the body affected or the specific molecules driving inflammation.
Sarcoidosis is an inflammatory disease that can manifest almost anywhere in the body, but most often shows up in the lungs, eyes, and on the skin. Researchers aren’t exactly sure what causes the immune system to overreact and form the clusters of cells, called granulomas. In the eyes, this results in uveitis, eyelid abnormalities, and optic neuropathy, among other signs.
“A patient would likely land in my care because of uveitis,” Hassman, who is also a specialist in the CU Department of Ophthalmology’s Center for Ocular Inflammation, explains. “They may be experiencing redness, blurry vision, floaters, light sensitivity, pain around the eyes, and potentially permanent loss of vision.”
Uveitis can be caused by a number of other diseases, such as syphilis. But certain signs, like granulomas, might key a physician into whether sarcoidosis could be the root source of the ocular inflammation and discomfort. Making the diagnosis requires finding evidence of granulomas in the lungs, lymph nodes or other organs.
Learning more about sarcoidosis and how it manifests in the eyes could benefit ophthalmologists, researchers, and patients who have the disease, along with paving the way for more personalized treatments.
Finding sarcoidosis subtypes
Researchers are just starting to understand the characteristics of sarcoidosis and how they differ in different parts of the body.
“There’s some great work showing that specific organ systems often manifest together in individual patients with sarcoidosis,” Hassman says. “Researchers have learned that there is a skin and lymph node phenotype, for example. That’s where we need to go with uveitis. First, we need to learn which clinical signs correlate into disease subtypes, then which molecules are characteristic of each disease subtype. From there, we can target those specific molecules and more effectively treat patients.”
This could lead researchers toward treatments that are better suited for an individual patient. There are approximately 200,000 cases of sarcoidosis in the U.S., with about 27,000 new diagnoses each year. While the disease can be mild for some patients, it can also be life-threatening and lead to lung and heart disease.
Hassman is currently recruiting uveitis patients for an observational study where she analyzes a sample from the eye using single-cell RNA sequencing to learn more about the molecules driving eye inflammation in individual patients. In time, Hassman envisions being able to create a database of patients with many types of uveitis that could help her and other researchers better understand the spectrum of immune response types found in the eyes.
“Through this study, we hope to place uveitis patients into groups that aren’t based on descriptive terms like ‘sarcoidosis’ but instead are based on treatable molecular features, like ‘IL-6-driven inflammation’ or ‘TNF-driven inflammation,’” she says.
Treatments with personalization in mind
For patients, it’s also helpful to have a defined cause or description of their ocular sarcoidosis.
“Patients want to know why this is happening to them,” Hassman says. “The better we are able to define the disease, the closer we are in helping them understand why this might have happened and what can be done to help.”
In the end, defining subtypes of sarcoidosis could save lives.
“Even if we give a patient a diagnosis of sarcoidosis, we don't really know how to best treat it right now,” Hassman says. “Improving our ability to define subtypes of disease, and then applying molecular techniques like the ones we are using in my lab, will help us understand what’s driving the inflammation and what is targetable with drugs.”
