Validation of the Rule of 7's for Identifying Children at Low-risk for Lyme Meningitis

Background: The Rule of 7's classifies children as low-risk for Lyme meningitis with the absence of the following: ≥7 days of headache, any cranial neuritis or ≥70% cerebrospinal fluid mononuclear cells. We sought to broadly validate this clinical prediction rule in children with meningitis undergoing evaluation for Lyme disease. Methods: We performed a patient-level data meta-analysis of 2 prospective and 2 retrospective cohorts of children ≤21 years of age with cerebrospinal fluid pleocytosis who underwent evaluation for Lyme disease. We defined a case of Lyme meningitis with a positive 2-tier serology result (positive or equivocal first-tier enzyme immunoassay followed by a positive supplemental immunoblot). We applied the Rule of 7's and report the accuracy for the identification of Lyme meningitis. Results: Of 721 included children with meningitis, 178 had Lyme meningitis (24.7%) and 543 had aseptic meningitis (75.3%). The pooled data from the 4 studies showed the Rule of 7's has a sensitivity of 98% [95% confidence interval (CI): 89%-100%, I²= 71%], specificity 40% (95% CI: 30%-50%, I²= 75%), and a negative predictive value of 100% (95% CI: 95%-100%, I²= 55%). Conclusions: The Rule of 7's accurately identified children with meningitis at low-risk for Lyme meningitis for whom clinicians should consider outpatient management while awaiting Lyme disease test results.