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FORT WORTH, Texas -- Childhood-onset systemic lupus erythematosus (SLE) differs from adult-onset disease in important ways, but treatment approaches generally have derived from the adult arena, a pediatric rheumatology expert said here.

In most population-based cohorts of SLE, 15%-20% of cases are diagnosed before the age of 18, most often from ages 12 to 14. More pediatric cases are in males than among adult patients.

"But there is no single sign or symptom seen only in adults or only in children," said Hermine Brunner, MD, of Cincinnati Children's Hospital Medical Center and scientific director of the Pediatric Rheumatology Collaborative Study Group.

There are patterns, however. Children typically have more acute onset than adults do and more multiorgan involvement, as well as fever and lymphadenopathy. Hematologic features also are more common, along with neuropsychiatric involvement.

"Most important, because of the impact on longevity and prognosis, is kidney involvement, which is 30% more common in children versus adults," Brunner said at the annual meeting of the Rheumatology Nurses Society. In some populations of pediatric lupus, up to 80% of children developed lupus nephritis within 5 years of diagnosis.

Pediatric lupus nephritis must be recognized and treated quickly, because a child with lupus nephritis has an almost 20 times higher risk of dying than age-matched peers, "and if you do not treat it appropriately and children develop end-stage renal disease, one in five will die from lupus nephritis with 5 years."

Moreover, most of the cost of pediatric SLE is for lupus nephritis, with almost 60% of hospitalizations for lupus in children being for kidney problems.

In general, treatment for childhood-onset SLE is based on standard approaches in adult disease, because there are no large randomized trials in pediatric disease that would directly address questions such as what are the appropriate drug doses and what would be the optimal treatment duration for children, she said.

"When we use medications for children we have to consider that they have longer life expectancy than adults with lupus, and there will still be growth and development."

One of the mainstay drugs for pediatric SLE is hydroxychloroquine, with good-quality evidence that antimalarials reduce disease activity and mortality in children. There also is good evidence that hydroxychloroquine helps maintain bone health, helps prevent thrombosis, and has protective effects against organ damage. Hydroxychloroquine also may help reduce the number of disease flares.

"Antimalarials should be used for all children with lupus unless contraindicated," Brunner stated, explaining that hydroxychloroquine slows down the innate immune system by stopping the crosstalk between toll-like receptors 7, 8, and 9, and makes plasma and dendritic cells sluggish, so they can't produce as much type 1 interferon.

It's advisable to keep the dose below 5 mg/kg/day, and possibly lower if they have lupus nephritis, because hydroxychloroquine is filtered through the kidneys. "We don't know how much. There's actually appallingly little known about hydroxychloroquine metabolism."

Steroids also are commonly used. "Actually, before steroids began to be used in the 1960s one in two children with lupus would die within 2 years," she said.

These drugs work better if given in divided doses (maximum 60-80 mg/day), which provides better inflammation control and an increase in efficacy of 15%-20%.

With regard to treatment for lupus nephritis, it's important to keep in mind that any child with lupus who has unexplained proteinuria should have a kidney biopsy. And if the child has been diagnosed with lupus nephritis, regardless of how well controlled, clinic visits should be every 3 months because of the constant potential for flare, Brunner said.

If the lupus nephritis is class III/IV, treatment should start within a month to prevent damage from developing. Current options include mycophenolate mofetil (Cellcept) and cyclophosphamide. Studies comparing these two agents have demonstrated that they are equivalent for reducing mortality in both adults and children. There also have been no differences between the two medications in preventing end-stage renal disease and in inducing complete remission.

"So it comes down to patient preferences and toxicity."

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