Lupus in Kids: Damage Starts Early Save

A new study sheds important light on the long-term outcomes of children diagnosed with systemic lupus erythematosus (SLE).

The most common form of organ damage in a large Canadian cohort was cataracts, which developed in 14% of the children, and avascular necrosis, which was seen in 10%, according to Earl Silverman, MD, of the Hospital for Sick Children (SickKids) in Toronto, and colleagues.

The study also found that the use of prednisone and immunosuppressives, particularly cyclophosphamide, predicted an increase in damage, and that antimalarial use protected against damage.

"Our study has identified prognostic factors that following validation in independent cohorts, clinicians may use in their patient management strategies to modify damage trajectory evolution," the researchers wrote in Arthritis Care & Research.
The study is the first to use a longitudinal design to measure disease evolution in childhood SLE, from diagnosis into adulthood. Other studies had looked at cross-sectional views of damage accrued.

The study included 473 cases (82%) from the SickKids pediatric lupus clinic. The median age at diagnosis was 14.1.
As patients got older, their care was transferred to an adult lupus clinic. The researchers used rheumatologists and family doctors, and other sources, to obtain information on the complete disease trajectory.

Of the 473 participants, 2% died and 14% were lost to follow-up. The mean duration of follow-up was 5.63 years, with the longest, 26.3 years.

The primary outcome was the SLE International Collaborating Clinics' American College of Rheumatology (SLICC/ACR) SLE damage index (SDI), a validated measure of irreversible damage in SLE.

There were 13 instances of cardiovascular damage in 10 patients, including 11 cerebrovascular accidents and two myocardial infarctions (MIs). The median age at time of cardiovascular damage was 16.8 years, and the two MIs occurred at ages 26.3 and 39.6.

Damage steadily accumulated over the course of the disease, and the damage trajectory did not plateau. The presence of potentially life-threatening disease manifestations at baseline predicted more rapid early increase in damage. Increased age and the number of baseline ACR criteria were associated with greater total damage, but did not affect the rate of the damage trajectory, the researchers reported.

The longitudinal SLE Disease Activity Index 2000 (SLEDAI-2K) score did not predict changes in damage trajectory, but individual items did predict a worsening in the damage trajectory. These included psychosis or confusional state, lupus headache, and fever.

The involvement of lupus headache reflected disease severity, because most patients had central nervous system (CNS) vasculitis, Silverman and colleagues noted.

Over the course of the disease, each 10 mg increment of prednisone exposure from 6 to 24 months before each visit predicted an increase in damage, and compared with Caucasians and Asian patients, those of Afro-Caribbean race had a persistently greater damage trajectory, starting early.

Antimalarial use from 6 months prior to a visit protected against an increase in damage -- "even in the face of high-dose prednisone and cyclophosphamide, which illustrated a window of protection, the authors wrote.

"We were able to show that the protective effects were continued only 6 months after exposure. Therefore, in order to achieve sustained benefits, clinicians need to encourage long-term adherence to antimalarials."

Adult outcomes were not available for all patients, and those lost to follow-up could have had significantly different outcomes, the researchers said, adding that another potential limitation was that they did not collect information on socioeconomic status and adherence to medication.

Asked for his opinion for this article, Daniel J. Lovell, MD, MPH, associate director of the Division of Rheumatology and professor of pediatrics at the University of Cincinnati Medical Center, called the study "important and unique," especially since most of the patients were followed into adulthood.

That damage continued to accrue throughout the observation period, and did not plateau as it has in a few smaller studies, "is a very important but unfortunate finding that lends support for the need of long-term, ongoing vigilance and aggressive treatment," he said.

Although some patients had been followed for over 20 years, the median follow-up was just over 5 years. "This does not represent a truly long-term study for many of the patients," Lovell said. "This underscores the importance of future studies from this cohort of patients."

In addition, the fact that two patients had MIs at a very young age highlights the "dramatic influence of SLE on cardiovascular risk."

The finding that higher doses of prednisone and powerful immunosuppressants were associated with higher trajectories for damage accrual may be confounded by the fact that these medications are used to treat more severe manifestations or flares, which themselves contribute to damage, Lovell explained.

He agreed with the authors that although hydroxychloroquine seemed to slow the rate of accrual of damage, the effect persisted for only 6 months after stopping the medication -- "so continued dosing is important."

Lovell also pointed out some of the study's encouraging observations, such as that although 36% of the patients had significant renal disease at onset, only 2% went on to have end-stage renal disease. And while most patients had CNS vasculitis at baseline, only 4% developed cognitive impairment