Mortality Easing in Pediatric Rheumatic Disease

Major Finding: Overall mortality among children with rheumatic diseases was lower than expected; and although SLE and some other rheumatic conditions were associated with higher mortality, the rates were lower than previously reported for those diseases in this age group.

Data Source: Data from the Indianapolis Pediatric Rheumatology Disease Registry on nearly 49,000 children who were followed for about 8 years.

Disclosures: The study was supported by the Northeast Ohio Chapter of the Arthritis Foundation. The authors had no disclosures.

A study that analyzed data on almost 49,000 children and adolescents enrolled in a U.S. pediatric rheumatology registry found that the overall mortality for pediatric rheumatic diseases was not increased when compared to the general population, results that require further follow-up but were described as “encouraging” by the authors.

“Even for those diseases and conditions associated with increased mortality, the rates were significantly lower than those reported in previous studies,” especially for systemic juvenile rheumatoid arthritis (JRA), childhood systemic lupus erythematosus (SLE), dermatomyositis (DM), and vasculitis, reported Dr. Philip J. Hashkes of the Cleveland Clinic and his associates.

The study, which they said was “the largest systematic mortality outcome study in pediatric rheumatology published to date,” analyzed mortality outcomes among the 48,885 children newly diagnosed with a rheumatic disease between 1992 and 2001 and enrolled in the Indianapolis PRDR (Pediatric Rheumatology Disease Registry), involving patients from 62 centers in the United States. Children with a malignancy were excluded. Patients were followed for a mean of 8 years.

Almost 64% had an inflammatory diagnosis, of which the majority (almost 40%) was JRA, followed by SLE in almost 6% and Raynaud's phenomenon in almost 5%. Arthralgia was the most common noninflammatory diagnosis, affecting 36% of those with a noninflammatory rheumatic disease. Almost 7,000 patients had more than one rheumatic diagnosis.

To compare the observed survival rates to the expected survival rates, the authors calculated the SMR (standardized mortality ratio, defined as the number of observed deaths divided by the number of expected deaths).

The mortality of the patients in the registry was significantly lower than was the expected mortality of the U.S. population, adjusted for age and sex. Overall, there were 110 deaths (0.23%) among the nearly 48,000 patients for whom complete data were available, for an SMR of 0.65.

Put another way: The 5-year survival rate was 99.77% for the entire group, and was slightly lower for those with connective tissue disease, systemic JRA, and those with primary vasculitis other than Kawasaki disease.

There were significant differences in the SMR for several diagnostic categories and specific diseases. SMR was significantly increased for the categories of connective tissue diseases and primary vasculitis, with the exception of Kawasaki disease and Henoch-Schönlein purpura (HSP). The SMR was significantly greater for SLE (3.06) and DM (2.64), but not for systemic JRA (1.8). The SMR was significantly decreased for pain syndromes (0.41) and arthralgia (0.23). The SMR did not differ significantly for other specific diseases, including all subtypes of JRA, Kawasaki disease, and HSP.

The SMRs in the group of patients with noninflammatory diseases (0.58) and those with inflammatory diseases (0.76) were significantly lower than in the general population; the difference was more significant in the noninflammatory group.

Of all the 110 deaths, 64 (58%) were in patients with an inflammatory disease. The rest, with the exception of one patient whose primary diagnosis was not known, were in patients with a noninflammatory disease.

In 39 cases (35%), the cause of death was related to the rheumatic diagnosis. Other causes of death included treatment complications in 11 patients (10%), non-natural causes in 25 (23%), and background disease in 23 (21%). In 12 (11%) patients, the cause of death was unknown or not clear.

The investigators found a significant correlation between the rheumatic diagnosis and cause of death: Among the 64 patients who had been diagnosed with an inflammatory disease before their death, 28 (44%) deaths were related to the diagnosis, for which they were being treated by a rheumatologist, compared with 11 (24%) of the 45 patients diagnosed with a noninflammatory disease.

The cause of death among the patients with SLE included renal disease in six cases, pancreatitis in two patients, pulmonary hemorrhage in one patient, and intracranial hemorrhage in one patient. Four died of an infection, including two who had had a bone marrow transplant. Of the patients with JRA who died, two died of macrophage activation syndrome, which the authors said is “probably currently the most common cause of death” in patients with systemic JRA. Two patients died of heart disease, one died of an infection, and one died of a secondary malignancy.