BERLIN—Doctors are presented with a 49-year-old woman with pain, weakness, and reduced endurance in the muscles, as well as stiffness in the morning. She is also found to have Raynaud’s phenomenon, symptoms of Sicca syndrome, dysphagia, and shortness of breath.
Lab tests show she is positive for antinuclear antibodies (ANAs), but also anticentromere antibodies, and she is negative for other kinds of myositis antibodies. A nailfold capillaroscopy is negative. Organ screening shows esophageal reflux and a completely normal electrocardiogram, with no signs of ischemia, pericarditis, or ventricular hypertrophy. A computed tomography (CT) scan shows no stenosis.
The woman—whose case was presented here at the European League Against Rheumatism (EULAR) 2012 Annual European Congress of Rheumatology, held June 6–9—might be considered at risk for having systemic sclerosis (SSc). But it is not that simple.
“This woman does not have the major criteria required for the diagnosis,” nor does she meet the 1980 ACR criteria for the classification of SSc, said Ulrich Walker, MD, professor of rheumatology at Felix-Platter and University Hospital in Basel, Switzerland.1 “So this woman, by definition, does not have scleroderma.” [Editor’s note: Because of deficiencies in the old criteria, the ACR and EULAR are supporting a joint project to develop new scleroderma classification criteria.]
She was ultimately diagnosed with undifferentiated connective tissue disease, possibly early SSc. Her case was used to highlight some of the potential pitfalls of handling myopathy in SSc.
A Tricky Diagnosis to Make
Although she does not meet the standard definition, studies have found that 47% of patients with Raynaud’s syndrome, and are ANA positive, end up developing SSc. “This woman is at considerable risk to develop scleroderma over time,” Dr. Walker said.
Dr. Walker warned against relying too much on serum creatinine kinase (CK) levels, because it’s been shown that 20% of patients with biopsy-proven myositis don’t have elevated CK. He suggested that serum CK and serum aldolase, together, can bring about a greater sensitivity. But muscle weakness is much more prevalent than serum CK levels in cases of diffuse SSc, he noted.
He also cautioned that serum CK-MB levels that are elevated aren’t necessarily an indication of myocardial involvement, so myocardial imaging might have to be done, helping to distinguish between impaired microcirculation, enhanced myocardial fibrosis, or inflammation and helping guide the intensity of treatment.
Dr. Walker also mentioned a small study his center performed using blood oxygen level–dependent (BOLD) magnetic resonance imaging, in which images are taken as a cuff inflates around the patient’s thigh and then relaxes. Twelve consecutive patients had more pronounced ischemia and lacked a reactive hyperemia compared to age- and gender-matched controls.
“In other words, patients with systemic sclerosis probably have quite pronounced microangiopathy early in their disease despite the fact that, with our normal tools, [they] lack clinical signs of that,” Dr. Walker said. “And I think that should be investigated.”
In the case of this 49-year-old patient, he noted, anticentromere antibodies were found, even though they’ve been shown to be protective against myositis—making this case “somewhat puzzling.”
Calcinosis with SSc
Another case-based presentation focused on calcinosis associated with SSc. The cases, out of the Royal Free Hospital in London, covered an array of severity and contexts for calcinosis.
There was a case of diffuse SSc with rheumatoid arthritis overlap, in which the patient had calcific periarthritis with significant functional problems. The patient was treated with adalimumab. A case of limited SSc, with recalcitrant digital calcinosis and ulceration, was treated with surgery.
A case of limited SSc was treated with minocycline and surgery, with surgery bringing the biggest benefit. Another case of limited SSc, but with debilitating calcinosis, has required large doses of opioids for the patient’s pain.
“Calcinosis is a really major morbidity for patients with systemic sclerosis”—with a diversity of ways to cause problems, said Christopher Denton, MD, professor of experimental rheumatology at Royal Free Hospital and University College of London Medical School.
Treatment is a challenge, and some of the cases show the reliance on surgery, Dr. Denton said. “Surgical management … really is perhaps the only approach to therapy that has unequivocal benefit in the right patient group,” he said. Minimally invasive approaches, using a dental drill or laser excision, have proven effective, he said.
Calcinosis can be assessed with radiography, CT scanning, ultrasound, and isotope bone scanning. But Dr. Denton stressed the importance of keeping function in mind. “We have got to look at the impact of the calcinosis, not just the extent and anatomical location,” he said. “Because it’s really the functional impact that is important and that our patients are troubled by.” This was seen in the case of the patient who had limited SSc, but whose calcinosis left her wheelchair bound.
The diversity of the calcinosis cases makes it hard to identify a unified approach. One attempt, detailed in a forthcoming article by Herrich et al (Rheumatology, in press) divides calcinosis into mild, moderate, and severe, depending on the density of the calcification and the number of sites, although Dr. Denton said the approach can be problematic because the effects can be devastating even in cases not classified as severe.
There are no drugs that are proven to help with calcinosis. Bisphosphonates have shown benefits in some studies but not in others. The antibiotic minocycline showed improvement in eight of nine limited cutaneous SSc patients at 50–100 mg a day. And the calcium-channel blocker Dilitiazem has been shown to be effective at high doses, but not low doses, Dr. Denton said.
TNF antagonists are a candidate, but that, too, is based on scant evidence. “There is a very limited amount of evidence to support the use of different treatments,” Dr. Denton said.
He stressed the importance of trials to understand the underlying genetics of calcinosis better and studies to get at associations and predictors that might lead to better interventions. He noted the start of the Scleroderma Clinical Trials Consortium and EULAR Scleroderma Trials and Research initiative to foster clinical trials on calcinosis in SSc. “This should be a research priority,” Dr. Denton said. “And certainly represents an unmet medical need.”
Thomas Collins is a freelance medical writer based in Florida.
