SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.
Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.
Dr. Virginia Steen
Nail Fold Capillaries/Digital Ulcers
For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.
Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.
"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.
Arthritis/Joint Involvement
Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.
Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).
"Hand arthritis is often quite mixed," Dr. Steen said.
Muscle Involvement
Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.
Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.
Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.
Skin Involvement
Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.
"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.
Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.
Gastrointestinal Involvement
Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.
"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.
Interstitial Lung Disease
Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.
"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.
Pulmonary Hypertension
Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.
A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.