It begins with cold hands.
Not just put-on-some-gloves cold. Instead, the fingers overreact to cold by turning white or blue and may become numb or tingly.
This hypersensitivity to cold, called Raynaud’s phenomenon, may occur alone, or it may be the first symptom of systemic scleroderma. A rare, autoimmune disease, scleroderma sometimes is known as the "disease that turns people to stone."
Months or even two or three years after the onset of Raynaud’s phenomenon, people with the systemic form of scleroderma usually notice swelling of the hands with an uncomfortable tight sensation. That’s followed by thickening and hardening of the skin that usually starts in the fingers and may spread to the hands, forearms, body, legs and feet.
The word “scleroderma” comes from the Greek “sclero,” meaning hard, and the Latin “derma,” meaning skin. The localized form of scleroderma — more correctly called morphea — is primarily a skin disease and does not affect the internal organs. However, the systemic form of scleroderma (systemic sclerosis or SSc) is much more complicated and serious.
“SSc is far more than a skin disease,” says Maureen Mayes, M.D., professor in the Division of Rheumatology and Clinical Immunogenetics and the Elizabeth Bidgood Chair in Rheumatology at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). “In most people SSc is a multi-organ system disease.”
With scleroderma, the immune system becomes activated, damages the small blood vessels and may cause excessive buildup of fibrous connective tissue, or scar tissue, in the lungs, heart, gastrointestinal tract, kidneys, muscles and joints, as well as the skin. It may cause difficulty breathing, trouble swallowing, joint pain or other complications.
Estimated to affect 300,000 people in the United States (200,000 with morphea and 100,000 with systemic disease), scleroderma affects primarily women who are 25 to 55 years old at onset. Although there is a genetic component, the exact cause of this noncontagious disease is not yet known.
Origins of scleroderma
“We know there are about 30 genes thus far — and there are probably more of them — that will increase a person’s susceptibility to SSc,” Mayes says.
“It’s rare, but occasionally we see that more than one family member will have scleroderma. Then we also see in other families that one member has lupus, someone else has scleroderma, and someone else has rheumatoid arthritis, so those families have susceptibility to multiple autoimmune diseases.”
There’s no explanation for occurrence of the disease in individuals who have none of the known susceptibility genes.
“Just having the genes is not adequate to cause the disease,” Mayes says. “People have to be exposed to something that triggers the disease, and that might not be a single thing. It could be a viral infection or a bacterial infection or some sort of environmental exposure. We’ve certainly looked into a lot for potential environmental exposures but have not yet found much that seems to be specific for people with scleroderma versus those without scleroderma.
“We don’t know what triggers the immune system to respond in this way. Partly because of that, although we can treat it, we can’t prevent or cure it,” says Mayes, who is a past president and a current director of the National Medical and Scientific Board of the United Scleroderma Foundation.
How it is treated
People with scleroderma typically see a rheumatologist first, then other specialists, depending on what organ systems are involved. The UT Physicians Scleroderma Clinic, which is directed by Mayes, coordinates all the subspecialists.
“We try to have a more holistic approach toward the diagnosis and management of scleroderma so we know what’s going on in the lungs, the heart, the kidneys and the GI tract and can help to coordinate therapy,” she says.
Patients generally take multiple medications, some just to treat symptoms. For milder cases, for example, there are medications for Raynaud’s phenomenon and for heartburn and reflux.
“One of the important things that we do in the scleroderma clinic is to monitor people with annual or biannual testing. Just because a patient doesn’t have lung disease today doesn’t mean that they might not get lung disease a year from now. So we get pulmonary function tests and sometimes chest CAT (computerized axial tomography) scans if it looks like the pulmonary function tests are abnormal. We have some treatments that, although not curative, can slow or stop the progression of the disease,” Mayes says.
“Our treatments have potential adverse effects, so you don’t want to give them to someone who’s stable and not worsening. But you want to be able to identify someone who is developing internal organ involvement. It’s better to get treatments started before a lot of damage has been done,” she adds.
Immunosuppressants are the major category of medications used against the overactive immune system. Unfortunately, in decreasing the activity of the immune system, the medications also can make people more susceptible to infections. To guard against serious side effects of some of the medications, the UT Physicians Scleroderma Clinic tests for hepatitis and TB before beginning treatment with immunosuppressants and treats those diseases first if they are present.
Clinical research progress
Results of a major study of a new treatment for early severe scleroderma were reported in January 2018 in the New England Journal of Medicine.
In this multicenter study, for which Mayes was one of the principal investigators, patients were treated with a high dose of chemotherapy to destroy the overactive immune system. The patients’ own immature stem cells — removed before beginning chemotherapy — were then infused to reconstitute the immune system. Because the stem cells are immature or “naïve,” they will not cause a recurrence of the autoimmune disease.
Most of Mayes’ patients who participated in the study did very well. Although some features of scleroderma remain — such as Raynaud’s, vascular damage and scar tissue in the lungs — those problems tend to stop progressing, and skin manifestations tend to improve significantly. Because there was a 3 percent mortality rate from destruction of the immune system, this treatment is appropriate only for people with severe disease and poor prognosis.
Mayes is optimistic about development of future treatments. She encourages people with scleroderma to participate in a clinical trial if they have the opportunity.
“I’ve been involved in almost every single treatment trial that has been conducted in scleroderma over the past 25 years. At first, there would be one trial and then two or three years later a second trial. Now we have six ongoing trials simultaneously, which is, I think, very hopeful that at least one of these medications is going to be effective,” she says.