Prospective evaluation of tolerance to unheated milk-boiled egg after baked milk-egg tolerance under 2 years.

BACKGROUND: The time to acquisition of tolerance to unheated milk and regular egg after achievement of tolerance to baked goods is not known. OBJECTIVE: To determine the time to acquisition of unheated-milk-regular-egg tolerance, after the tolerance of the baked forms, in children younger than 2 years. METHODS: An initial oral food challenge with baked milk (BM) and baked egg (BE) was performed on patients who were reactive to unheated milk-regular egg, respectively. Patients who were BM-BE tolerant were offered unheated-milk-regular-egg challenges, and patients who were BM-BE reactive were offered BM-BE challenges at an average of 3-month intervals. Food-induced atopic dermatitis was included. RESULTS: Thirty-six children with unheated-milk allergy (median age, 7.3 months [interquartile range (IQR), 6.0-13.5]) and 65 with regular-egg allergy (median age, 7 months [IQR, 5.8-11.0]) were included. Seven of 13 children who were BM tolerant acquired unheated-milk tolerance after a median 4.0 months (IQR, 2.0-7.0). Twelve of 23 children who were BM reactive acquired unheated-milk tolerance after a median 5.0 months (IQR, 3.0-8.0) after BM tolerance. Twenty-one of 29 children who were BE tolerant acquired regular-egg tolerance after a median 3.0 months (IQR, 1.0-6.0). Sixteen of 36 children who were BE reactive acquired regular-egg tolerance after a median 4.0 months (IQR, 2.0-6.8) after BE tolerance. CONCLUSION: Different tolerance rates were determined for baked products at different time points in the first 2 years of life. Unheated-milk-regular-egg allergy resolved in up to 65.5% and 75.5% of cases, respectively, in an average 4 to 5 months after acquisition of BM-BE tolerance. Baked-milk-baked-egg tolerance may be regarded as a precursor of tolerance.

A Prospective Assessment of Clinical Characteristics and Responses to Dietary Elimination in Food Protein-Induced Allergic Proctocolitis.

BACKGROUND: Some aspects of diagnostic elimination/challenge diets in food protein-induced allergic proctocolitis (FPIAP) are still poorly defined. OBJECTIVE: This study investigated the symptom spectrum, time required for resolution of each symptom, triggering foods, and risk factors for multiple food allergies (MFA) in FPIAP. METHODS: Infants referred with visible blood in stool were enrolled after etiologies other than FPIAP had been excluded. Laboratory evaluation, clinical features, and elimination/challenge steps were performed prospectively during diagnostic management. RESULTS: Ninety-one of 102 infants (53 boys) were diagnosed with FPIAP. Eleven children did not bleed during challenges. Visible blood in stool began before 2 months of age in 63.6% of the infants not diagnosed with FPIAP, compared with 18.9% of the patients with FPIAP (P = .003). Offending foods were identified as cow's milk (94.5%), egg (37.4%), beef (10.9%), wheat (5.5%), and nuts (3.3%). MFA was determined in 42.9% of patients. Multivariate logistic regression analysis identified atopic dermatitis (AD) (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.18-7.55, P = .021) and an eosinophil count ≥300 cells/µL (OR: 2.72, 95% CI: 1.09-6.80, P = .032) as independent risk factors for MFA. Blood and mucus in stool disappeared in a median 3 days (interquartile range [IQR]: 1-14.5 days) and 30 days (IQR: 8-75 days), respectively. CONCLUSIONS: A tendency to transient bleeding occurs in infants who present with bloody stool before 2 months of age. A 2-week duration of elimination for blood in stool is sufficient to reach a judgment of suspected foods for FPIAP. Mucus in stool is the last symptom to disappear. Concurrent AD suggests a high probability of MFA in FPIAP.

A Novel Homozygous Mutation in the MYO5B Gene Associated With Normal-Gamma-Glutamyl Transferase Progressive Familial Intrahepatic Cholestasis.

The genetic defect of MYO5B is usually associated with microvillus inclusion disease (MVID). MYO5B mutations are one of the rare causes of progressive familial intrahepatic cholestasis (PFIC) with normal/low gamma-glutamyl transferase (GGT). In this report, we discuss the case of a nine-month-old girl with low-GGT cholestasis whose next-generation sequencing (NGS) showed a homozygous splicing variation (c.3045+3A>T) on the MYO5B (NM_001080467) gene, which was a novel mutation. We identified that this mutation had a disease-causing effect in silico analysis.

Utility of fresh egg skin prick test and egg yolk specific immunoglobulin E for outgrowth.

BACKGROUND: In children younger than 2 years, studies evaluating the value of skin prick tests (SPTs) and specific immunoglobulin E (sIgE) results to predict persistence or resolution of egg allergy (EA) are limited. In addition, the value of egg yolk (EY) sIgE and fresh egg (FE) SPTs has not been well characterized. OBJECTIVE: To investigate the optimal decision points (ODPs) for outgrowing allergy with SPTs and sIgE tests for egg allergen preparations. METHODS: SPTs for FE, egg white (EW), and EY, sIgE tests for EW and EY, and oral food challenges (OFCs) were performed in children with suspected EA. Reactive patients strictly avoided all dietary egg. After 1 year, EA was reevaluated with addition OFCs, SPTs, and sIgE tests. RESULTS: A total of 81 children (median age, 7 months; age range, 2-24 months) were enrolled. Notably, 4 children with a history of anaphylaxis and 60 of 77 children with a positive challenge result underwent egg elimination. The 1-year follow-up OFC test was performed on 59 children. A total of 27 reacted to egg. No persistent patient had a follow-up SPT result for FE of 4 mm or less (positive predictive values of 100% and negative predictive value of 56% for outgrowth). The diameters of the initial SPT for FE decreased 50% or more in half of the patients who outgrew EA. The ODPs for outgrowing allergy for follow-up sIgE tests for EY and EW were 2.1 kU/L or less (positive predictive value of 86.2%) and 4.0 kU/L or less (positive predictive value of 84.6%), respectively. CONCLUSION: A SPT diameter for FE of 4 mm or less and sIgE values of 2.1 kU/L or less for EY and 4.0 kU/L or less for EW have a good positive predictive value for outgrowth of EA in children younger than 2 years.

A novel etiologic factor of highly elevated cholestanol levels: progressive familial intrahepatic cholestasis.

Background Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an uncommon cholestatic liver disease caused by mutations in the ATP binding cassette subfamily B member 4 (ABCB4) gene. Although PFIC3 is frequently identified in childhood, ABCB4 disease-causing alleles have been described in adults affected by intrahepatic cholestasis of pregnancy, hormone-induced cholestasis, low-phospholipid-associated cholelithiasis syndrome or juvenile cholelithiasis, cholangiocarcinoma and in sporadic forms of primary biliary cirrhosis. Cholestanol is a biomarker which is elevated especially in cerebrotendinous xanthomatosis and rarely in primary biliary cirrhosis (PBC) and Niemann Pick type C. Case presentation Here we report a Turkish patient with compound heterozygous mutations in the ABCB4 gene, who has hepatosplenomegaly, low level of high-density lipoprotein, cholestasis and high level of cholestanol. Conclusion This is the first PFIC3 case with a high cholestanol level described in the literature. There are very few diseases linked to increased cholestanol levels, two of which are CTX and PBC. From this case, we can conclude that a high cholestanol level might be another indicator of PFIC type 3.

Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry. RESULTS: The mean age of the patients was 13.4 ± 7.9 years, and the follow-up period was 3.4 ± 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency.

Head Circumference Charts for Turkish Children Aged Five to Eighteen Years.

INTRODUCTION: Most head circumference growth references are useful during the first years of life, but they are also useful for older children when screening for developmental, neurological, and genetic disorders. We aimed to develop head circumference growth reference charts for age, height, and waist circumference for Turkish children aged 5-18 years. METHODS: Head circumference, height, and waist circumference measurements were obtained from 5079 students aged 5-18 years from Izmit, Kocaeli Province, Turkey. The LMS method was used to construct reference centile curves. RESULTS: Head circumference measurements were strongly correlated with height (r=0.74), weight (r=0.76), and waist circumference (r=0.68). The mean head circumference values for boys were larger than those for girls at all ages. Compared with data from the United States, the World Health Organization, and other studies from Turkey, our data showed a decrease in head circumference at all ages for both sexes. CONCLUSION: Local growth charts can be used to evaluate head circumference growth in older Turkish children and adolescents.