Brain Abscess as Severe Presentation of Specific Granule Deficiency.

Severe invasive infections such as brain abscess in a child should prompt an immune evaluation. Specific granule deficiency (SGD) is a rare morphologic neutrophil granular defect characterized by reduced granules within neutrophils, absence of granule proteins, and bilobed nuclei. Patients are susceptible to invasive bacterial infections and Candida infections. Mutations in CCAT/enhancer binding protein epsilon (C/EBP-ε) are the most commonly described cause of SGD. The dihydrorhodamine assay is a quantitative and qualitative functional test that determines the oxidative burst and killing potential of neutrophils. Herein, we describe two brothers with specific granule deficiency. The index patient had a history of cellulitis twice in the first year of life and then presented at 13 months age with fever, leukocytosis, and right sided weakness. A large space occupying brain abscess was diagnosed. He underwent surgical drainage and cultures yielded Staphylococcus aureus. This infection prompted his diagnosis. His older brother had also been healthy but too had had several episodes of cellulitis. His brother too was diagnosed with SGD when family genetic screening was performed. Evaluation of the index patient included a peripheral smear that showed absent neutrophil granule presence. Forward and side scatter of whole blood via flow cytometry revealed a loss of granularity of neutrophils. A DHR was performed to rule out functional killing defects. After stimulation with PMA, neutrophils from the index patient displayed three distinct patterns, two with abnormal oxidase production, and two with reduced function. Both patients were ultimately diagnosed with SGD and remain on lifelong anti-bacterial prophylaxis. Diagnosis of SGD relies on establishing reduced or absent granularity within neutrophils. Lifelong anti-bacterial and anti-fungal prophylaxis is indicated. Hematopoietic cell transplantation has also been curative.

External caliper-based measurements of the modified percent depth as an alternative to cross-sectional imaging for assessing the severity of pectus excavatum.

BACKGROUND: Cross-sectional imaging (CSI) may be clinically unnecessary in the evaluation of pectus excavatum (PE). The purpose of our study was to prospectively evaluate the accuracy and reliability of the modified percent depth (MPD), derived from caliper-based external measurements, in identifying PE. METHODS: Children 11-21 years old presenting for evaluation of PE or to obtain thoracic cross-sectional imaging for other indications were measured to derive the Modified Percent Depth. The Haller Index (HI) and Correction Index (CI) were calculated from CSI. Receiver-Operator Characteristic (ROC) analysis was used to compare the sensitivity and specificity of MPD, HI, and CI. Interrater reliability was assessed using Spearman's correlation coefficient and Cohen's Kappa coefficient. RESULTS: Of 199 patients, 76 (38%) had severe PE. Median age was 16 years (range = 11-21). The median Modified Percent Depth was 21.4% (IQR = 16.2-26.3) among those with PE versus 4.1% (IQR = 1.7-6.4) in those without (p < 0.001). MPD ≥ 11% exhibited similar sensitivity and specificity to HI ≥ 3.25 and CI ≥ 10 for identifying PE (ROC 0.98 vs. 0.97 vs. 0.98, respectively, p = 0.41). With respect to interrater reliability, independent clinicians' caliper measurements exhibited 87% agreement when identifying MPD ≥ 11% (p < 0.001) with excellent correlation (Spearman's ρ > 0.71, p < 0.001). CONCLUSION: Caliper-based, physical examination measurements of the Modified Percent Depth reliably identify pectus excavatum and represent an alternative to CSI-based measurements for the assessment of PE. TYPE OF STUDY: Diagnostic test. LEVEL OF EVIDENCE: Level II.