It wasn’t long ago that scleroderma was viewed as a disease that followed a single clinical pathway. Then it was recognized that the degree of skin involvement predicted unique complications and long-term outcomes. Classification of patients into limited skin involvement (limited scleroderma) and widespread skin involvement (diffuse scleroderma) provided the first insight into the heterogeneity of the disease process.
That’s when curious clinicians started paying more attention to the finer details of the many ways scleroderma presented and changed over time. More attention to careful, sensitive testing that detected clinically occult disease made a difference as well.
“Over time, we have come to better understand the complexity of scleroderma and recognize multiple subtypes of disease,” said Fredrick M. Wigley, MD, the Martha McCrory Professor of Medicine at Johns Hopkins University School of Medicine. “What I call fine phenotyping, both clinically and with improved laboratory testing, has helped us understand that scleroderma is actually a very heterogeneous and dynamic disease process of which there are subtypes. The clinician needs to appreciate both the subtype of scleroderma and the stage the patient is in to better define what would be appropriate management at that point in time.”
Dr. Wigley will discuss the growing understanding of scleroderma during the Philip S. Hench, MD, Memorial Lecture: Scleroderma 2022: Moving to Precision Management on Sunday, November 13, from 8–9 a.m. ET, in Terrace Ballroom II and III of the Pennsylvania Convention Center. Meeting participants have the option to attend the lecture in person or on the meeting website via livestream, or to view the lecture on demand.
Recognizing that scleroderma has the potential to affect multiple organ systems was one of the early steps in phenotyping the disease. Skin involvement is the most visible manifestation, but scleroderma can affect the lungs, heart, kidney, and other organs. Patients may have just one organ system involved or multiple systems.
“We also understand that the biological processes that are common across all these subtypes vary,” Dr. Wigley continued. “Every article starts out by saying scleroderma is a multisystem disease that is in the autoimmune family, that there is fibrosis in the tissues and there is injury to small blood vessels. There are common features, but how scleroderma expresses itself in each patient is quite different.”
Research is beginning to unravel the pathogenesis of scleroderma. Cancer can trigger scleroderma in a subset of patients, although the precise roles played by patient factors, environment, and other contributors remain unclear.
Single-cell analysis of tissue biopsies, genomic profiling, and similar tools are advancing the basic science of scleroderma. Massive amounts of new data are being generated, Dr. Wigley said. The challenge is linking these novel molecular findings to clinical features in ways that can lead to more personalized management strategies and improved outcomes for patients.
“The state of the art of caring for scleroderma is recognizing that one drug will not knock it out,” he explained. “The disease process is complex and does not follow one pathway but a cluster of different pathways unique to the specific organ involved.”
Many of the genetic mutations seen in lupus and other autoimmune diseases are also seen in scleroderma, Dr. Wigley added. But scleroderma follows a different clinical course with unique features, including tissue fibrosis and vascular disease involving small blood vessels.
“Scleroderma is one of the most challenging rheumatic diseases,” he said, “It’s really a challenge in management. Understanding the patient’s phenotype and where they fall in the progression of disease will help identify the management approaches that are more likely to be effective.”