Three novel homozygous ITGB2 mutations among two patients with leukocyte adhesion defect type-1: Two case reports.

BACKGROUND: A leukocyte adhesion defect (LAD) is a rare primary immunodeficiency disorder. LAD type 1 (LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of ß2 integrin, which impairs leukocyte adherence to the endothelium. CASE SUMMARY: The first two cases of LAD-1 in Thailand presented with recurrent omphalitis, soft tissue infection, marked leukocytosis, and neutrophilia. One patient experienced delayed umbilical cord separation. Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. The results revealed two novel homozygous missense mutations, c.920C>T (p.Leu307Pro) in exon 8 and c.758G>A (p.Arg253His) in exon 7, and one novel homozygous nonsense mutation, c.262C>T (p.Gln88Ter) in exon 4, in the genomic DNA of the first and second patients, respectively. Heterozygous mutations were identified in the parents of both patients, suggesting a carrier status. The patients were administered intravenous antibiotics for infections with good clinical responses. Hematopoietic stem cell transplantation could not be performed due to the unavailability of matched donors. However, a significant decline in infections was observed after antibiotic prophylaxis. Several follow-up visits were conducted for both patients. They are currently 6 years old. CONCLUSION: Molecular analysis is essential for definitive diagnosis, early treatment implementation, and prevention of LAD-1 in future pregnancy.

Toxic epidermal necrolysis after first dose of Pfizer-BioNTech (BNT162b2) vaccination with pharmacogenomic testing.

Toxic epidermal necrolysis (TEN) is a rare and acute life-threatening condition and one of the severe cutaneous adverse drug reactions. There are limited data on TEN from the COVID-19 vaccine regarding its pathogenesis, treatment, and prognosis, particularly in children. We report a case of COVID-19 vaccine-induced TEN and the patient's human leukocyte antigen pharmacogenomic profile.

Accuracy of in-house alcohol-dissolved wheat extract for diagnosing IgE-mediated wheat allergy.

BACKGROUND: The standard method for diagnosing immediate wheat allergy is oral food challenge test (OFC). However, OFC can provoke anaphylaxis during the challenge process. Skin prick test (SPT) using commercial wheat extract yielded unsatisfactory result for diagnosis of wheat allergy. As a result, an in-house, alcohol-dissolved (Coca-10% EtOH) wheat extract was developed to improve accuracy of the SPT. OBJECTIVE: To determine the accuracy of in-house, alcohol-dissolved wheat extract in children with immediate wheat allergy. METHODS: This prospective cross-sectional study included children with history of immediate reaction after wheat ingestion. SPTs with commercial and in-house Coca-10% EtOH wheat extract were performed and wheat and omega-5 (ω-5) gliadin specific IgE (sIgE) were measured. Patients with no history of recent anaphylaxis after wheat ingestion underwent OFC with 31 grams of wheat flour. RESULTS: Thirty children were recruited. Thirteen of those had history of anaphylaxis after wheat ingestion. Eleven of the remaining 17 children (64.7%) had a positive result for wheat challenge test. Wheal size of 3 mm for both in-house and commercial wheat extract yielded the best accuracy for the test. Using these cutoff parameters, in-house Coca-10% EtOH wheat extract yielded 91.7% sensitivity, 66.7% specificity, and 86.7% accuracy. Comparatively, the commercial extract yielded 70.8% sensitivity, 100% specificity, and 76.6% accuracy. CONCLUSIONS: SPT using in-house Coca-10% EtOH wheat extract yielded better accuracy than commercial extract for diagnosing immediate type wheat allergy in children.

Age of resolution from IgE-mediated wheat allergy.

BACKGROUND: The natural history of wheat allergy varies among different countries. OBJECTIVE: To study the age of resolution from IgE-mediated wheat allergy and to define the predictors of wheat tolerance. METHODS: Patients with a history of immediate reactions after wheat ingestion were enrolled. Skin prick test (SPT) and measurement of serum specific IgE (sIgE) to wheat and ω-5 gliadin were performed. Oral challenge to wheat was performed to determine wheat tolerance. RESULTS: Fifty-five patients, aged 6 months to 12 years, were studied. The median age of wheat tolerance was 76 months (range 37-114 months). The percentage of children with wheat tolerance was 14.7% at age 2 years, 27% by age 4, 45.7% by age 5 and 69% by age 9. Predictors for wheat tolerance were SPT for wheat less than 3 mm of wheal diameter (hazard ratio 8.9), sIgE levels of wheat and ?-5 gliadin less than 0.35 (HR 4.3) and 0.35 kAU/L (HR 44), respectively, duration of onset of symptoms to time of physician diagnosis less than 36 months (HR 7.6) and no history of allergic rhinitis (HR 4.8). CONCLUSIONS: Forty percent of children with IgE-mediated wheat allergy develop tolerance by the age of 5 years. Size of SPT, IgE level of wheat and ω-5 gliadin, time from onset of symptoms to physician diagnosis and history of allergic rhinitis are helpful for predicting wheat tolerance.

Successful wheat-specific oral immunotherapy in highly sensitive individuals with a novel multirush/maintenance regimen.

We reported a successful oral immunotherapy (OIT) in 2 children with high wheat sensitivity (4 and 14 years old boys). Oral challenges indicated eliciting doses of 300 mg, and wheat flour of 30 mg. The OIT protocol includes 5 days of build-up phase in the hospital, intervening with 2 to 5 months of home maintenance phase. Patients could tolerate 45 g, and 60 g of wheat flour per day, respectively. We have demonstrated that OIT to a large amount of wheat in extremely sensitized patients could be achieved with a stepwise multi oral/maintenance regimen.