VIENNA — The prognosis for children with mixed connective tissue disease is highly variable, with some progressing to scleroderma and others developing systemic lupus erythematosus, but in a significant number of cases, the autoimmune disorder improves over the long term, Thomas J.A. Lehman, M.D., said at the annual European congress of rheumatology.
This condition was first described by G.C. Sharp and colleagues in 1972 as a syndrome that included severe myositis, pulmonary hypertension, Raynaud's phenomenon, and esophageal hypomotility. It was felt to be a variant of lupus because patients were antinuclear antibody positive, but many also had features that were not typical of lupus, such as nailfold capillary abnormalities, Gottron's papules, hypergammaglobulinemia, and synovitis. Renal findings almost never included diffuse proliferative glomerular nephritis, although membranous nephritis sometimes was present.
Subsequently, other groups have attempted to refine Sharp's criteria. But even today, precisely what constitutes mixed connective tissue disease remains controversial—there are no official, definitive criteria—and some textbooks categorize the condition as an undifferentiated connective tissue disease or an overlap syndrome.
“Whatever you choose to call it, this is a relatively distinct group that diverges strongly over time, and we don't yet know how to tell who is going to diverge in which direction,” he said at the meeting, which was sponsored by the European League Against Rheumatism.
Most patients are strongly antinuclear antibody positive, ribonucleoprotein antibody positive, and Small antibody negative. C3 and C4 are usually normal, and tests for antidouble-stranded DNA most often are negative. Some 20%–50% of patients also have thrombocytopenia.
Careful monitoring can help determine the direction in which the condition will evolve. Urinalysis, for example, can reveal if a patient has become Smith positive and is developing classic lupus. Signs of progressive respiratory compromise may suggest progression to scleroderma, which tends to have the worst outcomes for the patients.
“But in my experience, the most common outcome has been for them to get better,” said Dr. Lehman, chief of the division of pediatric rheumatology at the Hospital for Special Surgery in New York City, who cares for many of these children.
This good outcome, however, requires close monitoring for potentially serious—or lethal—events, such as sudden, overwhelming sepsis, he said.
“These patients are functionally asplenic, so if the child develops a fever and signs of infection are present, start antibiotics and worry about false alarms later,” he said.
And cough, shortness of breath, or other respiratory problems can signal pulmonary hypertension, so it's wise to suggest an echocardiogram and high-resolution CT, said Dr. Lehman, who is also professor of clinical pediatrics, Weill Medical College of Cornell University, New York City.
The key is treating the individual's symptoms, and this can include the use of low-dose corticosteroids, hydroxychloroquine, and methotrexate, with calcium channel blockers for Raynaud's phenomenon.
“Monitoring the levels of IgG and hemoglobin, as well as the erythrocyte sedimentation rate, will tell you whether your treatment is adequately controlling the disease process,” he said at the meeting, which was sponsored by the European League Against Rheumatism.
“I've never had to use any of the immunosuppressive agents, such as cyclophosphamide or mycophenylate mofetil, at least in the early stages before the disease more fully delineates itself,” he said.