ABSTRACT
The current diagnostic marker of Lyme neuroborreliosis (LNB), the Borrelia burgdorferisensu lato antibody index (AI) in the cerebrospinal fluid (CSF), has insufficient sensitivity in the early phase of LNB. We aimed to elucidate the diagnostic value of PCR for B. burgdorferisensu lato in CSF from children with symptoms suggestive of LNB and to explore B. burgdorferisensu lato genotypes associated with LNB in children. Children were prospectively included in predefined groups with a high or low likelihood of LNB based on diagnostic guidelines (LNB symptoms, CSF pleocytosis, and B. burgdorferisensu lato antibodies) or the detection of other causative agents. CSF samples were analyzed by two B. burgdorferisensu lato-specific real-time PCR assays and, if B. burgdorferisensu lato DNA was detected, were further analyzed by five singleplex real-time PCR assays for genotype determination. For children diagnosed as LNB patients (58 confirmed and 18 probable) (n = 76) or non-LNB controls (n = 28), the sensitivity and specificity of PCR for B. burgdorferisensu lato in CSF were 46% and 100%, respectively. B. burgdorferisensu lato DNA was detected in 26/58 (45%) children with AI-positive LNB and in 7/12 (58%) children with AI-negative LNB and symptoms of short duration. Among 36 children with detectable B. burgdorferisensu lato DNA, genotyping indicated Borrelia garinii (n = 27) and non-B. garinii (n = 1) genotypes, while 8 samples remained untyped. Children with LNB caused by B. garinii did not have a distinct clinical picture. The rate of detection of B. burgdorferisensu lato DNA in the CSF of children with LNB was higher than that reported previously. PCR for B. burgdorferisensu lato could be a useful supplemental diagnostic tool in unconfirmed LNB cases with symptoms of short duration. B. garinii was the predominant genotype in children with LNB.
Subject(s)
Borrelia burgdorferi Group/genetics , Borrelia burgdorferi Group/isolation & purification , DNA, Bacterial/cerebrospinal fluid , Lyme Neuroborreliosis/diagnosis , Molecular Diagnostic Techniques/methods , Real-Time Polymerase Chain Reaction , Antibodies, Bacterial/cerebrospinal fluid , Child , Child, Preschool , DNA, Bacterial/genetics , Female , Genotype , Humans , Lyme Neuroborreliosis/cerebrospinal fluid , Male , Norway , Prospective Studies , Sensitivity and SpecificityABSTRACT
BACKGROUND: Current markers of Lyme neuroborreliosis (LNB) in children have insufficient sensitivity in the early stage of disease. The B-lymphocyte chemoattractant CXCL13 in the cerebrospinal fluid (CSF) may be useful in diagnosing LNB, but its specificity has not been evaluated in studies including children with clinically relevant differential diagnoses. The aim of this study was to elucidate the diagnostic value of CSF CXCL13 in children with symptoms suggestive of LNB. METHODS: Children with symptoms suggestive of LNB were included prospectively into predefined groups with a high or low likelihood of LNB based on CSF pleocytosis and the detection of Borrelia antibodies or other causative agents. CSF CXCL13 levels were compared between the groups, and receiver-operating characteristic analyses were performed to indicate optimal cutoff levels to discriminate LNB from non-LNB conditions. RESULTS: Two hundred and ten children were included. Children with confirmed LNB (n=59) and probable LNB (n=18) had higher CSF CXCL13 levels than children with possible LNB (n=7), possible peripheral LNB (n=7), non-Lyme aseptic meningitis (n=12), non-meningitis (n=91) and negative controls (n=16). Using 18 pg/mL as a cutoff level, both the sensitivity and specificity of CSF CXCL13 for LNB (confirmed and probable) were 97%. Comparing only children with LNB and non-Lyme aseptic meningitis, the sensitivity and specificity with the same cutoff level were 97% and 83%, respectively. CONCLUSION: CSF CXCL13 is a sensitive marker of LNB in children. The specificity to discriminate LNB from non-Lyme aseptic meningitis may be more moderate, suggesting that CSF CXCL13 should be used together with other variables in diagnosing LNB in children.
Subject(s)
Chemokine CXCL13/cerebrospinal fluid , Lyme Neuroborreliosis/diagnosis , Lyme Neuroborreliosis/epidemiology , Adolescent , Antibodies, Bacterial/blood , Antibodies, Bacterial/cerebrospinal fluid , Borrelia burgdorferi Group/immunology , Child , Child, Preschool , Female , Humans , Lyme Neuroborreliosis/immunology , Male , Predictive Value of Tests , Prospective StudiesABSTRACT
We present a case of an 11-year-old boy originally from a Middle East country. He presented with blue nodules and flat blue lesions in skin/subcutis. The lesions involved greater parts of his trunk over weeks; he had increasing migrating pain located to joints and a slight feeling of systemic illness, but no fever. His blood tests were normal except for CRP 21 and ESR 25. We could not find any rheumatic or vasculitis marker, any recent viral infection or chest pathology on X-ray. His spleen was borderline large. MRI showed inhomogeneous marrow and lytic lesions. A bone marrow biopsy was performed and at the same time his skin biopsy from 2 weeks earlier was reviewed using immunohistochemistry. The diagnosis was blastic plasmacytoid dendritic cell neoplasm (BPDCN), an extremely rare leukemia. This is the first known case in Norway. He started NOPHO-2008 ALL extra high risk protocol, had possible eye involvement and therefore extra intrathecal cytostatics, and had a stem cell transplant 6 months after treatment started. He is now well without further treatment 16 months after transplant.
