Toward the Development of Criteria for Global Flares in Juvenile Systemic Lupus Erythematosus

Objective. To develop a definition of global flare in juvenile systemic lupus erythematosus (SLE) and derive candidate criteria for measuring juvenile SLE flares. Methods. Pediatric rheumatologists answered 2 Delphi questionnaires to achieve consensus on a common definition of juvenile SLE flare and identify variables for use in candidate flare criteria. The diagnostic accuracy of these candidate flare criteria was tested with data from juvenile SLE patients (n = 98; 623 visits total). Physician-rated change in the juvenile SLE course (worsening, yes/no) between visits served as the criterion standard. Results. There was 96% consensus that a a flare is a measurable worsening of juvenile SLE disease activity in at least one organ system, involving new or worse signs of disease that may be accompanied by new or worse SLE symptoms. Depending on the severity of the flare, more intensive therapy may be required. Variables suggested for use in flare criteria were: physician-rated disease activity (V1), patient well-being, protein: creatinine ratio, a validated disease activity index (V2), the Child Health Questionnaire physical summary score (V3), anti-double-stranded DNA antibodies, erythrocyte sedimentation rate, and complement levels. Using multiple logistic regression, several candidate flare criteria were derived with area under the receiver operating characteristic curve (AUC) as high as 0.92 (sensitivity >= 85%, specificity >= 85%); classification and regression tree analysis suggested that V1, V2, and V3 suffice to identify juvenile SLE flares (AUC 0.81; sensitivity = 64%, specificity = 86%). Conclusion. Consensus about a definition of global disease flare for juvenile SLE has been obtained and promising candidate flare criteria have been developed. These will need further assessment of their ease of use and accuracy in prospective study.