COEUR D’ALENE, ID. – Pediatric chronic cutaneous lupus erythematosus transforms into systemic disease in one-quarter of cases, and if it’s going to do so, it’ll typically be within the first year after diagnosis, according to a retrospective study.
"Importantly, no one developed end-organ damage through the end of follow-up, perhaps suggesting that SLE arising in pediatric patients with CCLE follows a more indolent, benign course, just as we’ve seen in previous studies in adults with CCLE with transformation to SLE," Dr. Lisa Arkin observed at the annual meeting of the Society for Pediatric Dermatology.
Dr. Lisa Arkin
If that is indeed true, it’s good news for pediatric CCLE patients and their families because it sets them apart from the others who develop SLE prior to adulthood. Twenty percent of all cases of SLE present before age 20, and in general they tend to follow a more aggressive course than adult-onset SLE, with a higher frequency of end-organ involvement necessitating sustained immunosuppression, as well as higher mortality, noted Dr. Arkin, recently appointed as head of pediatric dermatology at Rush University Medical Center, Chicago.
Pediatric CCLE is a rare and little-studied disease. Its most common form is discoid LE, characterized by scaling, telangiectasias, atrophy, follicular plugging, and scarring.
Much more is known about adult discoid LE, a far more common condition. Less than 5%-10% of adults with discoid LE develop SLE, and when they do, the systemic manifestations are more likely to be benign than is typical in adult SLE patients whose systemic disease was not preceded by discoid LE, the pediatric dermatologist explained.
Because so little is known about pediatric CCLE, she conducted a retrospective study including 45 affected patients seen at Lurie Children’s Hospital of Chicago. Seven of the 45 presented initially with concurrent CCLE and SLE. The remaining 38 were followed for a median of 4.4 years, during which 9 patients (24%) transitioned to SLE. Of note, that 1-in-4 risk of transformation from skin to systemic disease is spot-on with the results of the three previous small retrospective studies of pediatric CCLE, the most recent of which was reported 6 years ago from Brazil (Pediatr. Dermatol. 2008;25:163-7).
Of the 7 patients in Dr. Arkin’s study with concurrent CCLE and SLE at presentation, 6 had discoid LE, as did 34 of the 38 with only CCLE at presentation who were followed for development of SLE.
Of the 38 patients with only CCLE at presentation, 12 (32%) had disease limited to the skin throughout follow-up.
Another 17 (45%) with only CCLE at presentation developed laboratory abnormalities during follow-up without transitioning to SLE, including 14 with antinuclear antibodies. Nine of these patients developed more than two laboratory abnormalities. Notably, all had been on hydroxychloroquine ever since the onset of their CCLE. This suggests the intriguing possibility that hydroxychloroquine – an immunomodulatory agent rather than an immunosuppressant – may favorably alter the natural history of disease progression in this young population, according to Dr. Arkin. That’s been shown to be the case in studies conducted in adult military personnel, where long-term follow-up of troops randomized to hydroxychloroquine for antimalarial prophylaxis delayed the diagnosis of SLE, lowered the rate of autoantibody accumulation, retarded renal damage, reduced the risk of infection, and improved overall survival (Lupus 2007;16:401-9).
Patients with concurrent CCLE and SLE presented at a considerably younger age: a mean of 8.7 years old, compared with 13.3 years of age for those with only CCLE.
No formal guidelines exist for monitoring patients with CCLE. Based upon her study findings, Dr. Arkin recommended that "it seems reasonable" to perform a meticulous physical exam and review of systems and obtain laboratory tests on a quarterly basis, particularly in the first year following diagnosis, when the risk of transformation to SLE is highest. The quarterly lab workup should include a complete blood count and complete metabolic panel, urinalysis, complement, antiphospholipid antibodies, and antinuclear antibodies with titer.
"I think one of the big questions which has not been answered is, should all kids with CCLE get oral hydroxychloroquine? There are no studies in children. The only FDA-approved indication is for antimalarial prophylaxis, although it’s certainly used commonly off-label for pediatric CCLE and also for SLE," she said.
The major side effects of oral hydroxychloroquine in children include retinal toxicity, which is dose-dependent, along with GI upset, headaches, and vivid dreams.
Dr. Arkin observed that while a randomized trial of hydroxychloroquine to delay or prevent SLE in high-risk individuals is warranted, she was unable to identify any predictors of transformation from CCLE to SLE in her study, despite an extensive search.