Newborn-onset chronic urticaria as the first manifestation of NLRP3 mosaicism

Objectives: A 7-month-old boy presented with generalized urticaria since the first week of life, without any other clinical manifestation. Cow's milk allergy was ruled out. His development was normal for his age. Maternal history was significant for COVID-19 infection in the third trimester of pregnancy with mild symptoms. Family history was significant for dermatographism in a maternal uncle. Hives were migratory with no single lesion persisting more than 24 h. There were no recognizable triggers and only relieved for 1-2 days after each vaccination. Patient was treated with optimal doses of antihistamines without improvement. Method(s): Laboratory tests and further studies were performed Results: Laboratory tests were normal including complete blood testing, circulating autoantibodies and infectious studies. C-reactive protein level and erythrocyte sedimentation rate were elevated. Due to chronic urticaria of newborn onset unresponsive to antihistamines a monogenic autoinflammatory disease was suspected. A targeted gene panel covering causative genes revealed the unreported p.Gly307Ala variant in the NLRP3 gene with a variant allele frequency (VAF) of 3% compatible with gene mosaicism. NLRP3 variant was classified as "likely pathogenic" based on its location, where a different variant has been reported as causing a severe form of cryopyrin-associated periodic syndromes (CAPS), and bioinformatic analyses. As expected, the variant was absent in patient's parents supporting for its de novo nature. Vision and hearing exams were normal. Treatment with canakinumab will start soon. Discussion(s): CAPS are dominantly-inherited autoinflammatory diseases caused by gain-of-function NLRP3 variants. These variants are often germline, but in some reported cases the variants are postzygotic causing gene mosaicism as in the patient here described. We believe that the mild presentation in our patient, despite having a likely pathogenic variant, may be explained by the low VAF. The genetic diagnosis in our patient allowed early initiation of anti-IL-1 treatment, which probably will prevent the development of other CAPS manifestations.

NUTRITIONAL MONITORING THROUGH THE WHATSAPP® APPLICATION: A POST-COVID-19 PANDEMIC INNOVATION

Background/Purpose: The Covid-19 pandemic has restricted in person care at our cleft treatment center, delayed patient turnout, and led to financial losses and an increased number of missed scheduled appointments. Thus, we have sought new ways to monitor the nutritional status of infant patients with clefts, by using the WhatsApp® application, so as to conduct timely nutritional interventions and to prevent malnutrition and anemia. The purpose was to monitor the nutritional status of newborn babies with cleft, using the WhatsApp® application, and to validate its use. Methods/Description: 71% of internet users in Brazil use WhatsApp® to send and receive messages. This application is easy to use, with privacy ensured by cryptography. This research project was approved by the Institutional Review Board. The protocol established: 1) new cases of infants up to 30 days old, with cleft lip and/or cleft palate;2) consent form signed by parent or guardian;3) the first appointment was in person;with mothers receiving training and guidance to send information about their children's height and weight every month;4) data comparisons were conducted against WHO benchmarks (WAZ score between 0 and - 1 = healthy weight;between - 1 and - 2 = nutritional risk;< - 2 = underweight);6) nutritional interventions considering RDI's. Results: 18 patients were followed up by regular data submission through the WhatsApp® application;8 had cleft lips, 3 cleft palates, and 7 cleft lip and palates. Among these patients, 1 had a gastrostomy tube, 2 had cow milk protein allergy, and 1 had cardiac disease. Thus far, 8 have already been submitted to lip surgery, and 10 are waiting to reach the appropriate age for surgery. Twelve were classified as coming from low-income families, and 6 from medium income families. Most of them (no. = 17) travelled between 100-500 km to receive care, and 1 more than 100 km. Eight received transportation and food subsidized by public funds, and 10 used their own funds. Thirteen children were fed breast milk for 120 days, 8 were breast fed directly and 5 were fed pumped breast milk;5 were fed formula. Nine began eating additional foods at 6 months, the remaining patients were not old enough for that yet. Eleven children had normal weight (eutrophic) since the onset, 3 were malnourished when the study began and recovered after about 54 days, 4 were at risk when the study began and recovered after about 26.5 days. No patient had to delay surgery because of anemia (mean Hb = 11.45g/ dL). Nutritional interventions included encouraging breast feeding and different breastfeeding positions, guidance regarding the appropriate concentration of infant formula and how /when to introduce of additional foods. Milk formula, bottles, scales, and measuring tapes were donated. Conclusions: The use of the WhatsApp® application for nutritional follow up proved to be a valid and effective way tomonitor the patients' growth and development, yielding efficient nutritional recovery.

Efficacy and safety of baked milk oral immunotherapy in children with severe milk allergy: A randomized, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions. OBJECTIVE: We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in children allergic to baked milk. METHODS: Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated. RESULTS: Eleven of 15 (73%) BMOIT participants reached the primary end point, tolerating 4044 mg of baked milk protein after 12 months of oral immunotherapy, compared with 0 of 15 (0%) on placebo. The median maximum tolerated dose and median change from baseline was significantly higher in the BMOIT group than in the placebo group (median maximum tolerated dose, 4044 mg vs 144 mg; P = .001; median change in maximum tolerated dose of 3900 mg vs 0 mg, P = .0001). Dose-related reactions were common, but more than 95% in both groups were mild. There was no significant change in cow's milk- or beta lactoglobulin-IgE from baseline for either group. Cow's milk-sIgG4 did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only, with more improving while on placebo compared with BMOIT. Most children and adolescents in the BMOIT group directly reported improvement in at least 1 domain. CONCLUSIONS: BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.

Elevated Cow's Milk-Specific IgE Levels Prior to Oral Immunotherapy Decrease the Likelihood of Reaching the Maintenance Dose.

BACKGROUND: Food desensitization via oral immunotherapy (OIT) is gaining acceptance in clinical practice. Owing to adverse reactions, the duration of the buildup phase until a maintenance dose is achieved may be prolonged, and in a minority of cases, OIT is stopped. OBJECTIVE: We aimed to assess factors associated with the probability of reaching the maintenance dose in cow's milk (CM) OIT. METHODS: We collected data from patients undergoing CM OIT at the Montreal Children's Hospital, BC Children's Hospital, and Hospital for Sick Children. We compared univariable and multivariable Cox regressions to evaluate sociodemographic factors, comorbidities, clinical characteristics, and biomarkers at study entry associated with the likelihood of reaching a maintenance dose of 200 mL of CM. RESULTS: Among 69 children who reached 4 mL of milk, the median age was 12 years (interquartile range, 9-15 years); 59% were male. Median duration of buildup phase from 4 to 200 mL was 24.0 weeks (interquartile range, 17.7-33.4 weeks). After adjusting for age and sex, higher baseline levels of specific IgE antibodies for α-lactalbumin (hazard ratio [HR] = 0.80; 95% confidence interval [CI], 0.67-0.95), ß-lactoglobulin (HR = 0.86; 95% CI, 0.76-0.98), casein (HR = 0.82; 95% CI, 0.72-0.94), and total CM (HR = 0.79; 95% CI, 0.65-0.97) were associated with a decreased probability of reaching maintenance. In addition, for every 10-mL increase in CM tolerated at entry challenge, the probability of reaching maintenance increased by 10%. CONCLUSIONS: The data suggest that higher levels of CM-specific IgE decreased the likelihood of reaching maintenance, whereas an increased cumulative CM dose at entry challenge increased the likelihood. Assessing these factors before therapy may assist in predicting the success of CM OIT.

Linseed allergy in an infant: A rare but increasing allergen

Case Report: With the growing trend of incorporating seeds in diet, hypersensitivity reactions have been progressively occurring but are rarely suspected. Linseed is a plant from the Linaceae family, and its seeds are increasingly used in bread. Despite being identified as an allergen capable of causing anaphylaxis, case reports are scarce. Female infant, 11 months old, with atopic dermatitis (AD), has been under cow's milk (CM) avoidance diet in the last 3 months due to CM allergy. At 10 months old, 15 minutes after ingesting a maze and sweet potato's bread, a perioral, axillar, and ear's pruriginous erythema developed, as well as nasal, palpebral, and malleolar angioedema. It was medicated with second-generation H1 antihistamine with symptom resolution after 6 hours. She avoided that bread and tolerated wheat bread. Prick to prick tests were positive for the suspected bread but negative for maze flour and raw and cooked sweet potato. After a detailed analysis of the bread's composition, linseed was identified, and prick to prick tests were positive with it. Due to COVID-19 restrictions, the patient has not yet performed oral challenge. A linseed allergy was the most likely diagnosis. Thus, we recommended avoiding this seed or any food that can contain it. Crossreactivity with other foods (wheat, peanut, rapeseed) and rape pollen is poorly understood, and its clinical relevance has not yet been determined. Hence, we did not perform any further investigation. This was a rare finding, and we did not find any report on infancy. This case should raise awareness for a growing trend of seed hypersensitivity. Therefore, this group of foods should be taken into account while we're investigating suspected allergic reactions to cereals and other grains.

COVID-19 Vaccines in Children with Cow's Milk and Food Allergies.

The COVID-19 pandemic is the most challenging global health crisis of our times. Vaccination against COVID-19 plays a key role to control the current pandemic situation. The risk of allergic reactions to new COVID-19 vaccines is low. However, there is a debate on the safety in allergic patients following post marketing findings by different agencies. Our aim is to understand from current experiences whether children with cow's milk or food allergy are at higher risk than a general population for allergic reactions to COVID-19 vaccines. Current data indicate that patients with a history of allergy to cow's milk or other foods, even if severe, should receive COVID-19 vaccine in a setting with availability of treatments for anaphylactic reactions and under medical supervision. Recipients should be discharged after a protracted observation period of 30 min if no reaction developed.