Alyson Kakakios

Food Protein-Induced Enterocolitis Syndrome: 16-Year Experience

Objective. The goal was to examine the demographic characteristics, causative foods, clinical features, treatments, and outcomes for children presenting with acute food protein-induced enterocolitis syndrome. Methods. This was a retrospective study of children with food protein-induced enterocolitis syndrome who presented to the Childrens Hospital at Westmead (Sydney, Australia) over 16 years. Results. Thirty-five children experienced 66 episodes of food protein-induced enterocolitis syndrome. The mean age at initial presentation was 5.5 months. Children frequently experienced multiple episodes before a correct diagnosis was made. Twenty-nine children reacted to 1 food, and 6 reacted to 2 foods. Causative foods for the 35 children were rice (n = 14), soy (n = 12), cows milk (n = 7), vegetables and fruits (n = 3), meats (n = 2), oats (n = 2), and fish (n = 1). In the 66 episodes, vomiting was the most common clinical feature (100%), followed by lethargy (85%), pallor (67%), and diarrhea (24%). A temperature of <36°C at presentation was recorded for 24% of episodes. A platelet count of >500 × 109 cells per L was recorded for 63% of episodes with blood count results. Only 2 of the 19 children who presented to an emergency department with their initial reactions were discharged with correct diagnoses. Additional investigations of food protein-induced enterocolitis syndrome episodes presenting to the hospital were common, with 34% of patients undergoing abdominal imaging, 28% undergoing a septic evaluation, and 22% having a surgical consultation. Prognosis was good, with high rates of resolution for the 2 most common food triggers (ie, rice and soy) by 3 years of age. Conclusions. Misdiagnosis and delays in diagnosis for children with food protein-induced enterocolitis syndrome were common, leading many children to undergo unnecessary, often painful investigations. Decreased body temperature and thrombocytosis emerge as additional features of the syndrome.

Rice: a common and severe cause of food protein induced enterocolitis syndrome.

Objective: To examine and compare the characteristics of food protein-induced enterocolitis syndrome (FPIES) caused by rice and cow’s milk/soy. Design: Retrospective study of children presenting with FPIES to the Children’s Hospital at Westmead, NSW, Australia, over a 16-year period. Results: There were 14 children with 26 episodes of rice FPIES compared with 17 children with 30 episodes of cow’s milk (n = 10) or soy (n = 7) FPIES. Children with rice FPIES were more likely to have FPIES caused by other foods (36%) than children with FPIES caused by cow’s milk/soy (0%). Rice caused more episodes of FPIES before a correct diagnosis was made (median 4 (range 1–4) vs median 2 (range 1–4)) and triggered more severe reactions with higher rates of intravenous fluid resuscitation (42% vs 17%) than reactions caused by cow’s milk/soy. Conclusions: This study highlights the emerging importance of rice, a food commonly thought to be “hypoallergenic”, as a significant trigger of FPIES. Paediatricians should be aware that rice not only has the potential to cause FPIES, but that such reactions tend be more severe than those caused by cow’s milk/soy.

Safety of food challenges to extensively heated egg in egg-allergic children: a prospective cohort study

Many children with IgE‐mediated allergy to egg can tolerate egg in baked foods. However, the clinical characteristics and severity of reactions of egg‐allergic children who react to baked egg at open food challenge (OFC) are not well defined.

A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy

Background: Epidemiologic evidence suggests delayed introduction of egg might not protect against egg allergy in infants at risk of allergic disease. Objective: We sought to assess whether dietary introduction of egg between 4 and 6 months in infants at risk of allergy would reduce sensitization to egg. Methods: We conducted a randomized controlled trial in infants with at least 1 first‐degree relative with allergic disease. Infants with a skin prick test (SPT) response to egg white (EW) of less than 2 mm were randomized at age 4 months to receive whole‐egg powder or placebo (rice powder) until 8 months of age, with all other dietary egg excluded. Diets were liberalized at 8 months in both groups. The primary outcome was an EW SPT response of 3 mm or greater at age 12 months. Results: Three hundred nineteen infants were randomized: 165 to egg and 154 to placebo. Fourteen infants reacted to egg within 1 week of introduction (despite an EW SPT response <2 mm at entry) and were unsuitable for intervention. Two hundred fifty‐four (83%) infants were assessed at 12 months of age. Loss to follow‐up was similar between groups. Sensitization to EW at 12 months was 20% and 11% in infants randomized to placebo and egg, respectively (odds ratio, 0.46; 95% CI, 0.22–0.95; P = .03, χ2 test). The absolute risk reduction was 9.8% (95% CI, 8.2% to 18.9%), with a number needed to treat of 11 (95% CI, 6–122). Levels of IgG4 to egg proteins and IgG4/IgE ratios were higher in those randomized to egg (P < .0001 for each) at 12 months. There was no effect on the proportion of children with probable egg allergy (placebo, 13; egg, 8). Conclusions: Introduction of whole‐egg powder into the diets of high‐risk infants reduced sensitization to EW and induced egg‐specific IgG4 levels. However, 8.5% of infants randomized to egg were not amenable to this primary prevention.

Baked egg food challenges – clinical utility of skin test to baked egg and ovomucoid in children with egg allergy

Many children with IgE‐mediated egg allergy can tolerate products containing extensively heated (baked) egg. Aside from food challenge, there are no tests which reliably predict tolerance to baked egg in egg‐allergic individuals.

A comparison of IL-2 levels in nasopharyngeal and endotracheal aspirates of babies with respiratory syncytial viral bronchiolitis

BACKGROUND Cytokines such as IL-2 are thought to be important in the pathogenesis of respiratory tract inflammation. Cytokine levels in nasopharyngeal aspirates (NPAs) have been used as a measure of respiratory inflammation in children with viral infections, but it is unclear whether they reflect levels in the lower respiratory tract. OBJECTIVE We sought to assess the correlation between IL-2 levels in the nasopharyngeal and endotracheal secretions of children intubated with respiratory syncytial virus (RSV)-positive bronchiolitis. METHODS NPA and endotracheal aspirates were collected concurrently from intubated infants with RSV-positive bronchiolitis. IL-2 levels were assayed by ELISA, and the results were compared according to collection site. RESULTS Nine paired specimens were collected. IL-2 levels ranged from 31 pg/mL to 8040 pg/mL. No significant difference was found in the geometric mean IL-2 values from the 2 collection sites. The intraclass correlation coefficient between NPA IL-2 levels and endotracheal aspirate IL-2 levels was 0.83. CONCLUSION IL-2 levels in NPAs are comparable with those in the lower respiratory tracts of infants with RSV-positive bronchiolitis. NPA cytokine levels provide a simple and useful means of assessing respiratory tract inflammation.

Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing

Roifman Syndrome is a rare congenital disorder characterized by growth retardation, cognitive delay, spondyloepiphyseal dysplasia and antibody deficiency. Here we utilize whole-genome sequencing of Roifman Syndrome patients to reveal compound heterozygous rare variants that disrupt highly conserved positions of the RNU4ATAC small nuclear RNA gene, a minor spliceosome component that is essential for minor intron splicing. Targeted sequencing confirms allele segregation in six cases from four unrelated families. RNU4ATAC rare variants have been recently reported to cause microcephalic osteodysplastic primordial dwarfism, type I (MOPD1), whose phenotype is distinct from Roifman Syndrome. Strikingly, all six of the Roifman Syndrome cases have one variant that overlaps MOPD1-implicated structural elements, while the other variant overlaps a highly conserved structural element not previously implicated in disease. RNA-seq analysis confirms extensive and specific defects of minor intron splicing. Available allele frequency data suggest that recessive genetic disorders caused by RNU4ATAC rare variants may be more prevalent than previously reported.

The emergence of resistant pneumococcal meningitis—implications for empiric therapy

Background: Following the emergence of penicillin and cephalosporin resistant pneumococcal meningitis in the United States, inclusion of vancomycin in empiric therapy for all suspected bacterial meningitis was recommended by the American Academy of Pediatrics. Few data are available to evaluate this policy. Aims: To examine the management and clinical course in relation to antibiotic therapy of a large unselected cohort of children with pneumococcal meningitis in a geographic area where antibiotic resistance has recently increased. Methods: Retrospective review of all cases of pneumococcal meningitis in a defined population (Sydney, Australia), 1994–99. Results: A total of 104 cases without predisposing illnesses were identified; timing of lumbar puncture (LP) was known in 103. Resistance to penicillin increased from 0 to 20% over the study period. Only 57 (55%) had an early LP (prior to parenteral antibiotics); 55 (96%) had organisms on Gram stain. Severe disease (intensive care admission or death) increased significantly from 57 cases with early LP (28%) to 33 with delayed LP (42%) to 13 with no LP (62%). Evidence of pneumococcal infection was available within 24 hours in 85% of those with delayed or no LP. Outcome was not related to empiric vancomycin use, which increased from 5% prior to 1998 to 48% in 1999. Conclusion: LP is frequently delayed in pneumococcal meningitis. Based on disease severity, empiric vancomycin is most justified when LP is deferred. If an early LP is done, vancomycin can be withheld if Gram positive diplococci are not seen.

Detection of Chromosomal Breakpoints in Patients with Developmental Delay and Speech Disorders

Delineating candidate genes at the chromosomal breakpoint regions in the apparently balanced chromosome rearrangements (ABCR) has been shown to be more effective with the emergence of next-generation sequencing (NGS) technologies. We employed a large-insert (7–11 kb) paired-end tag sequencing technology (DNA-PET) to systematically analyze genome of four patients harbouring cytogenetically defined ABCR with neurodevelopmental symptoms, including developmental delay (DD) and speech disorders. We characterized structural variants (SVs) specific to each individual, including those matching the chromosomal breakpoints. Refinement of these regions by Sanger sequencing resulted in the identification of five disrupted genes in three individuals: guanine nucleotide binding protein, q polypeptide (GNAQ), RNA-binding protein, fox-1 homolog (RBFOX3), unc-5 homolog D (C.elegans) (UNC5D), transmembrane protein 47 (TMEM47), and X-linked inhibitor of apoptosis (XIAP). Among them, XIAP is the causative gene for the immunodeficiency phenotype seen in the patient. The remaining genes displayed specific expression in the fetal brain and have known biologically relevant functions in brain development, suggesting putative candidate genes for neurodevelopmental phenotypes. This study demonstrates the application of NGS technologies in mapping individual gene disruptions in ABCR as a resource for deciphering candidate genes in human neurodevelopmental disorders (NDDs).

Intravenous immunoglobulin to treat severe atopic dermatitis in children: a case series.

Abstract:  Severe cases of atopic dermatitis (AD) may require systemic immunosuppression to achieve disease control. Unfortunately, some cases continue to be refractory to management or develop unacceptable adverse effects. There are limited reports of the use of intravenous immunoglobulin (IVIg) in the treatment of severe AD, but results are inconsistent. In a retrospective study, we report 10 children with severe AD refractory to systemic immunosuppression and maximal topical therapy who were treated using IVIg. The children received monthly IVIg for an average of 24 months. This resulted in a significant improvement in symptoms, with fewer infection‐related exacerbations and hospitalizations, allowing systemic immunosuppression to be tapered. The effect was associated with a significant decrease in serum immunoglobulin E and was sustained after cessation of IVIg in 50% of cases. No significant side effects attributable to the IVIg infusions were noted. In this cohort of children with severe AD and recurrent cutaneous infections, IVIg provided an effective treatment with minimal side effects and significant benefits in school attendance and quality of life.