Several inborn errors of immunity are caused by defects in the general DNA repair machinery as exemplified by the T-B- RS-SCID condition owing to impaired resolution of programmed DNA double strands breaks introduced by RAG1/2 during V(D)J recombination. The genome instability generally associated with these conditions results in an increased propensity to develop malignancies requiring genotoxic based anti-cancer treatments. Moreover, the extent of immune deficiency often calls for hematopoietic stem cell transplantation as a definitive treatment, thus also demanding genotoxic based conditioning regimen prior to transplantation. In both cases, the underlying general DNA repair defects may result in catastrophic iatrogenic consequences. It is therefore of paramount importance to assess the functionality of the DNA repair apparatus prior to any genotoxic treatment when the exact molecular cause of the disease is unknown. For this purpose, two simple assays can be used on patient’s derived peripheral blood lymphocytes. 1) The PROMIDISα biomarker, based on the next generation sequencing analysis of the TCRα will highlight specific signatures of DNA repair deficiencies. 2) Direct analysis of the sensitivity of peripheral lymphocytes to ionizing radiations will formally identify patients at risk to develop toxicity towards genotoxic based treatments.
To the EditorReply to Stefano Miceli SopoFirst of all we want to thank for giving us an opportunity to reply to this correspondence (1), acknowledging the correspondence authors important point about the recommendation of introducing well-cooked, but not raw or uncooked pasteurized hen’s egg as part of complementary feeding.We agree that the evidence-base is sparse, with just two trials about cooked egg contributing to the low to moderate certainty evidence in our review (2) and guideline (3). These studies were in different populations (4, 5). We highlighted these points in the guideline, and the subgroup analysis from the Perkin study (6) was used only as supporting material, and for estimating the amount of egg that could be used. It is correct that the Natsume study included infant at higher risk due to eczema, but that was the case for both groups, and outcome was assessed by controlled challenges as described in the systematic review (2).As set out in the guideline, the process took into account expert insight weighing up benefits and harms, costs, feasibility, standard practice and patient preferences, in addition to published evidence. Weighing up all of these factors, the task force decided that the potential benefits outweighed potential harms in the case of well-cooked egg. One relatively large study found a 29% absolute decrease in the proportion of high risk infants with egg allergy at 1 year when very small amounts of egg were introduced (RR 0.22, 95% CI 0.08 to 0.54) (4). And two trials found no adverse effects (4, 5). It is likely feasible for many families to introduce well-cooked egg as part of complementary feeding, including in baked goods. The potential benefits do not outweigh the harms for uncooked egg, so the task force did not suggest trying this approach.The task force included representatives from many countries and specialties, and followed a robust process when reviewing evidence and debating potential recommendations. As the correspondence authors note, this recommendation is in line with other key guidelines. Whilst the correspondence authors may not agree with specific recommendations, the process used to debate and vote on them was systematic and took into account perspectives from across the world, including those from organisations representing patients and their families. Furthermore, a public consultation process sought feedback prior to publication, which further reinforced consensus about this recommendation.As is the case with all guidelines, the EAACI food allergy prevention guideline provides suggestions for clinicians to consider, alongside the needs of individual patients and local contexts and customs. The guideline is not prescriptive and does not override clinical judgement ad individual circumstances. Given the lack of likely harm, the convenience of this approach and best available evidence to date, the task force stands by its suggestion that clinicians in countries where egg allergy is an issue discuss with families the potential and desire to introduce small amounts of well-cooked egg into the infant diet when appropriate as part of complementary feeding. This need not be from the beginning of complementary therapy and the amounts may be very small.The guideline suggests half of a well-cooked, small egg twice a week, which may be in the form of a hard-boiled egg, well-cooked egg pasta, bread or baked goods, for example (p. 850). There is no evidence of significant harm, and it is likely that infants in many parts of the world may be exposed to egg in their diet anyway. There is no need to avoid this to prevent egg allergy, and in the opinion of the EAACI task force, introducing it may have benefits.Susanne Halken, Professor a, ProfessorAntonella Maria Muraro b, ProfessorGraham Roberts c, ProfessorDebra de Silva d, ProfessorOn behalf of On behalf of the EAACI Prevention Guideline Task Forcea Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, DenmarkbDepartment of Women and Child Health, Food Allergy Referral Centre Veneto Region, Padua University Hospital, Padua, Italyc Clinical and Experimental Sciences and Human Development in Health, Faculty of Medicine, University of Southampton, Southampton, UK. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UKdThe Evidence Centre Ltd, London, UKReferencesStefano Miceli Sopo, Dario Sinatti, Francesco Mastellone, Giulia Bersani, Mariannita Gelsomino. Comment on Halken et al. Pediatr Allergy Immunol . 2022de Silva D, Halken S, Singh C, et al. Preventing food allergy in infancy and childhood: systematic review of randomised controlled trials. Pediatr Allergy Immunol . 2020;31(7):813-826Halken S, Muraro A, de Silva D, et al. EAACI guideline: Preventing the development of food allergy in infants and young children (2020 update). Pediatr Allergy Immunol. 2021;32(5):843-858.Natsume O, Kabashima S, Nakazato J, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 92 2017;389(10066):276-286.Perkin MR, Logan K, Tseng A, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374(18):1733-1743.Perkin MR, Logan K, Bahnson HT, et al. Efficacy of the enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy. J Allergy Clin Immunol. 2019;144(6):1606-1614.
Threshold and safe ingestion dose among infants sensitized to hen’s eggMasatoshi Mitomori,a Noriyuki Yanagida,aMakoto Nishino,a Kyohei Takahashi,aKen-ichi Nagakura,a Kiyotake Ogura,aMari Takei,b Sakura Sato,b Motohiro EbisawabaDepartment of Pediatrics, National Hospital Organization, Sagamihara National Hospital, Kanagawa, JapanbClinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, JapanRunning title: Threshold and safe ingestion dose of egg
Background: Genetic areas of FOXP3 TSDR, HLA-G upstream of CpG island 96, CpG41 and CpG73 islands of the HLA‐DRB1 and HLA-DQB1 genes respectively, previously documented to display immune modulatory properties, were subjected to epigenetic/genetic analysis to assess their influence in IgE-mediated food allergy (FA) development in children. Methods: 64 orally challenged and IgE- tested food allergic subjects together with 44 controls were recruited. Targeted pyrosequencing analysis, to detect DNA methylation status and genetic variations was utilized and experimental results obtained were analysed by statistical software platform and correlated to clinical data. Also, transcription factor (TF) binding sites at study areas were unmasked by the JASPAR prediction database. Results: Parents’ smoking was significantly correlated with aberrant methylation patterns, regardless food allergic or control status. HLA-G promoter region showed a trend for hypomethylation in food allergic subjects, with one of the CG sites displaying significantly decreased methylation values. Rs1233333, residing within HLA-G promoter region preserved a protective role towards DNA methylation. Variable methylation patterns were recorded for CpG41 of the HLA‐DRB1 gene and hypermethylation of the region was significantly correlated with the presence of (Single Nucleotide Polymorphisms) SNPs. TFs’ recognition sites, located at studied genetic areas and exerting pivotal regulatory biological roles, are potentially affected from divergent DNA methylation status. Conclusions: We propose that HLA-G expression is triggered by food derived allergens, providing a TregFoxP3-/HLA-G+ subpopulation generation and direct immune-tolerance. Furthermore, clear evidence is provided for the underlying co-operation of genetic polymorphisms with epigenetic events, mainly at CpG41 island of HLA-DRB1 gene, which need an extended investigation and elucidation.
Background Cold urticaria (coldU) is associated with substantial morbidity and risk of fatality. Data on coldU in children are sparse. We aimed to evaluate the clinical characteristics, management, risk of associated anaphylaxis, and resolution rate of coldU in a pediatric cohort. Additionally, we sought to compare these metrics to children with chronic spontaneous urticaria (CSU). Methods We prospectively enrolled children with coldU from 2013-2021 in a cohort study at the Montreal Children’s Hospital and an affiliated allergy clinic. Data for comparison with participants with solely CSU were extracted from a previous study. Data on demographics, comorbidities, severity of presentation, management, and laboratory values were collected at study entry. Patients were contacted yearly to assess for resolution. Results Fifty-two children with cold urticaria were recruited, 51.9% were female and the median age of symptom onset was 9.5 years. Most patients were managed with second generation H1-antihistamines (sgAHs). Well-controlled disease on sgAHs was negatively associated with concomitant CSU (adjusted odds ratio (aOR)=0.69 [95%CI: 0.53, 0.92]). Elevated eosinophils were associated with cold-induced anaphylaxis (coldA) (aOR=1.38 [95%CI: 1.04, 1.83]), which occurred in 17.3% of patients. The resolution rate of coldU was 4.8 per 100 patient-years, which was lower than that of CSU (adjusted hazard ratio=0.43 [95%CI: 0.21, 0.89], P<10-2). Conclusion Pediatric coldU bears a substantial risk of anaphylaxis and a low resolution rate. Absolute eosinophil count and co-existing CSU may be useful predictive factors.
To the Editor,Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE) mediated food allergy that predominantly affects infants and is characterized by repetitive vomiting that occurs 1–4 h after the ingestion of causative food. The etiology and underlying mechanisms of FPIES are not well understood. Recently, egg yolk (EY) has been recognized as a major causative food of FPIES.1,2 Most FPIES patients achieve tolerance with age;3 however, the practice management of EY-associated FPIES (EY-FPIES) has yet to be established. In a preliminary analysis of EY-FPIES, we found that the patients who acquired tolerance to EY had been diagnosed at a significantly younger age than non-tolerated patients despite no difference in the age of onset between both patients. This suggested that the early diagnosis and intervention is beneficial for tolerance acquisition in EY-FPIES. To investigate this further, we compared clinical outcomes between the early and late diagnosis of EY-FPIES.The present study enrolled 21 patients with EY-FPIES (1) diagnosed by positive oral food challenge (OFC) tests at our hospital between April 2018 and April 2021 who (2) subsequently underwent OFC to evaluate tolerance acquisition (re-OFC) at least once. The open OFC was performed by ingestion of a single dose once or three divided doses every 30 minutes. OFC was considered positive for FPIES based on delayed abdominal reactions without immediate skin or respiratory reactions. After confirmation by OFC, we instructed all patients to continue complete elimination of EY, regardless of threshold doses of OFC. We retrospectively collected data from electronic medical records on sex, age of first ingestion of EY, disease onset, first visit to our hospital, diagnosis, specific IgE (sIgE) to EY measured by ImmunoCAP test at diagnosis, asymptomatic histories of EY consumption before onset, the number of symptomatic episodes before diagnosis, the period between the first ingestion of EY and diagnosis of EY-FPIES, and age of tolerance acquisition. Tolerance acquisition was defined by (1) negative OFC and (2) the ability of daily EY consumption without FPIES reactions for three months at home. We divided the patients into the following two groups according to their age at the time of diagnosis: the early diagnosis (ED) group (<12 months) and the late diagnosis (LD) group (≥12 months), and compared the clinical features between both groups. A sIgE value higher than 0.35 UA/ml was defined as positive. Statistical analyses were performed using GraphPad Prism 9. The Mann-Whitney U test was used to compare nonparametric independent samples between the groups. Tolerance acquisition during follow-up was analyzed using a Kaplan–Meier survival curve and the log-rank test. P-value <0.05 was considered statistically significant. This study was approved by the Institutional Review Board of the KKR Sapporo Medical Center (2021-06).Patients’ characteristics are shown in Table 1. The ED group consisted of 12 patients (57.1%), 10 (83.3%) of whom acquired tolerance to EY, and the LD group consisted of nine patients (42.9%), three (33.3%) of whom acquired tolerance to EY. Among 21 patients with EY-associated FPIES, a total of 35 re-OFCs were performed, with a median interval of seven months (interquartile range [IQR], 6–11 months) (Figure 1). The median ages that re-OFC proved negative in ED and LD groups were 16 and 26 months, respectively (p = 0.014) (Table 1). The time to tolerance acquisition was significantly longer in the LD group than that in the ED group, as shown in the Kaplan–Meier analysis (log-rank, p = 0.0015) (Figure 2). The median ages of onset and first visit to our hospital were significantly younger in the ED group than those in the LD group (Table 1). All patients had a history of three episodes (IQR 2–6) of asymptomatic consumption before onset. Although the median age of the first introduction of EY in the ED group was younger than that in the LD group (six months vs. eight months, p = 0.004), there was no significant difference in the median number of asymptomatic consumptions before onset and the period between the first introduction and onset between the groups. The period between the first introduction of EY and FPIES diagnosis was shorter in the ED group than that in the LD group (2.5 months vs. 7 months, p = 0.0002).We demonstrated that the ED group achieved tolerance at a higher rate than the LD group, suggesting that early diagnosis and intervention predict favorable prognosis in EY-FPIES. Consistent with a previous report,4 all patients with EY-FPIES had histories of asymptomatic consumption before disease onset. Involvement of both innate and adaptive immunities with resultant proinflammatory cytokine production has been suggested in the pathology of acute FPIES.5 Our results suggest that the development of EY-FPIES requires sensitization of the adaptive immune system. T helper (Th)2 and Th17 cells are considered as key players of the immune response in FPIES,6 which is reflected by local infiltration of eosinophils and neutrophils, respectively. Adaptive immunity of infants shows dynamic changes with a rapid decline of regulatory T cells and maturation of Th17, while Th2 dominance is preserved.7 Additionally, the intestinal barrier function immaturity was also observed, resulting in a higher permeability of antigens across the intestines.8 Thus, early infants may be predisposed to FPIES because of immunological as well as anatomical immaturity. Although both ED and LD groups shared a similar interval between the first introduction of EY and onset, the period between the onset and diagnosis in the ED group was significantly shorter than that in the LD group. Our results suggest that an earlier elimination of EY after onset prevents the complete development of EY-FPIES.The median age at onset in the 21 patients with EY-FPIES was 8 months (IQR, 7–9 months), which is comparable to previous reports.9 Similar to another report,9 13 patients (65.0%) achieved tolerance at the median age of 16 months. This is earlier than the median age reported in a European series that demonstrates a 50% cumulative probability of resolution at the age of 41 months.10Notably, the median age of diagnosis is older (12 months) in that study compared with that in our series. Thus, the different clinical courses may attribute to differences in age of diagnosis. Otherwise, the clinical course may depend on ethnicity. In 2017, the Japanese Society of Pediatric Allergy and Clinical Immunology recommended the early introduction of EY to infants with a high risk for IgE-mediated egg allergy. This might have increased the number of early-onset EY-FPIES in Japan. Our results suggest that a first re-OFC seven months after the diagnosis is reasonable for preventing unnecessary food avoidance in EY-FPIES.Our study is limited by a retrospective review of a small number of patients from a single institute. Additionally, accidental exposures after diagnosis occurred in one patient in the LD group, influencing the scheduling of re-OFC. Moreover, we evaluated solely patients with a confirmational diagnosis by OFC, which might be insufficient to reflect the whole heterogeneity of EY-FPIES.Conclusively, the ED group achieved tolerance in EY-FPIES earlier compared with the LD group. Early diagnosis and complete elimination of EY may be beneficial for EY-FPIES.
Abstract Background: The level of pollen in Korea has increased over recent decades. Research suggests that pollen-food allergy syndrome (PFAS) may be more frequent in childhood than previously recognized. We aimed to investigate the prevalence and characteristics of PFAS in children aged 6–10 years from a general population-based birth cohort. Methods: We analyzed 930 children from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) birth cohort. Allergic diseases were diagnosed annually by pediatric allergists. The skin prick tests were performed with 14 common inhalant allergens and four food allergens for children aged 3 and 7 years. Results: Of the 930 eligible children, 44 (4.7%) aged 6–10 years were diagnosed with. The mean age at onset was 6.74 years. PFAS prevalence was 7.2% among children with allergic rhinitis (AR) and 19.1% among those with pollinosis, depending on comorbidity. PFAS was more prevalent in schoolchildren with atopic dermatitis, food allergy, and sensitization to food allergens and grass pollen in early childhood. In schoolchildren with AR, only a history of food allergy before 3 years increased the risk of PFAS (aOR 2.971, 95% CI: 1.159–7.615). Conclusion: Food allergy and food sensitization in early childhood was associated with PFAS in schoolchildren with AR. Further study is required to elucidate the mechanism by which food allergy in early childhood affects the development of PFAS.
Background: Previous studies reported controversial results regarding the association between allergic disorders and ADHD/ASD. The aim of this article is to investigate whether allergic disorders are associated with ADHD/ASD in a large cohort of pediatric patients. Methods: A retrospective study using the pediatric (0-18 year) database (ICD-9-CM codes) of Clalit Health Services during the years (2000-2018). Diagnosis of all disorders was made by specialist physicians. Results: 117,022 consecutive non-selective allergic children diagnosed with one or more allergic disorder (asthma, rhinitis. conjunctivitis, skin, food, or drug allergy) and 116,968 non-allergic children were enrolled to our study. The mean follow-up period was 11±6 years. The presence of allergic disorders in early childhood (mean age of allergic diagnosis 4.5± 4.3 years) in boys as well as in girls, significantly increased the risk to develop ADHD (O.R 2.45, CI 2.39-2.51; P<0.0001), ASD (O.R 1.17, CI 1.08-1.27; P<0.0001) or both ADHD+ASD (O.R 1.5, CI 1.35-1.79; P<0.0001). Children with more than one allergic comorbidity revealed a much higher risk. In a multivariable analysis (adjusted for age at study entry, number of yearly visits and gender) the risk of allergic children to develop ADHD and ADHD+ASD, but not ASD alone, remained significantly higher. Conclusion: Allergic disorder in early childhood significantly increased the risk to develop ADHD, and to a less extend ASD, in later life.
Background: Cross-reactivity between wheat and other cereals is an essential issue in the management of wheat allergy. Few studies have reported in vitro cross-reactivity in immediate-type wheat allergy. This study aimed to examine cross-reactivity of the three fractions (albumin/globulin, gliadin, and glutenin fractions) among cereals in children with wheat allergy. Methods: Sera from 128 children with immediate-type wheat allergy were collected. We measured specific immunoglobulin E (sIgE) levels against each fraction of wheat, barley, and rye by using an enzyme-linked immunosorbent assay (ELISA). Cross-reactivities of each fraction among wheat, barley, and rye were examined via inhibition ELISA. Results: All subjects were sensitized to all the fractions of wheat, and also those of barley and rye. The wheat sIgE levels were significantly higher than those of barley and rye in all the fractions (p ≤ 0.001) and were significantly correlated with sIgE levels to them in each fraction (r = 0.887–0.969, p < 0.001). On inhibition ELISA, wheat inhibited the IgE binding to most of the solid phases at the lower protein levels compared to barley and rye in all fractions. Conclusions: In children with immediate-type wheat allergy, sensitization to all the three fractions of wheat was observed. In addition, they showed sensitization to barley and rye caused by in vitro cross-reactivity with wheat in each fraction. When managing children with wheat allergy, sensitization to barley and rye caused by the cross-reactivities should be considered.
Drug-induced enterocolitis syndrome with paracetamol (acetaminophen) in a 12-month-old-old boy B.Pascalab, B.Evrardac, E.Merlinbc, C.Egronb, B.Bonnetac, E.Michaudba Service d’immunologie, hôpital Gabriel Montpied, Clermont-ferrand, Franceb Service de pédiatrie générale, hôpital Estaing, Clermont-ferrand, Francec Université Clermont Auvergne, Clermont ferrand, FranceTo the Editor,Drug-induced enterocolitis syndrome (DIES) is a new clinical presentation similar to food protein-induced enterocolitis syndrome (FPIES). It was described for the first time in 2014 by Novembre et al.(1). More and more cases have been described since and clinical diagnostic criteria have recently been proposed. (2)A 12-month-old boy was referred to our Pediatric Allergy Unit for a suspected drug hypersensitivity. At age 10 months, he was admitted to the pediatric emergency room for vomiting and fever, previously treated with two intake of intrarectal paracetamol (15 mg/kg every 6 hours), the last one 4 hours before admission. He had no previous history (and no allergic history). During the initial examination, we observed asthenia, paleness, no fever (after antipyretics) and tachycardia, followed by four episodes of mucus vomiting without diarrhea. An occlusive syndrome was suspected. Given the hemodynamic disorders, continued fluid resuscitation was performed. Blood tests showed an isolated hyperleukocytosis with neutrophils (11.08 G/L). Eosinophils (0.210 G/L), lymphoid cells (7.25 G/L), the ionogramm and CRP (4.9 mg/L) were normal. Blood gas revealed a compensated respiratory alkalosis (lactates 2.2 mmol/L, methemoglobinemia 1.3%). No tryptase or specific IgE test was performed. Abdominal ultrasound was normal. Microbiological workup was negative. The next day, he was still irritable with several night vomiting episodes. He was discharged with some clinical improvement (diagnosed viral disease).By questioning the parents, they noticed that their child presented digestive disorders’ events at home since birth, which coincided with the 5 times intake of Paracetamol, twice orally and then intrarectally. The symptoms appeared systematically from the first intake. In the child’s medical history, we found no rhythmicity related to meals or other etiologies. His father has a well-known pollen and Penicillin allergies. By reviewing the emergency room observations (Figure 1), we noticed systematic digestive disorders approximately 3h to 6h after each paracetamol intake, explaining the moderate initial clinical improvement.Four months later, skin prick tests (10 mg/mL) and intradermal tests (0.1 mg/mL) were negative. The drug oral challenge (Table 1) was positive: repeated vomiting, marked pallor, lethargy, and crying without cutaneous or respiratory symptoms 2 hours after the last paracetamol intake. Rehydration and corticosteroid therapy brought a complete clinical recovery. No mast cell degranulation was observed (normal tryptase levels: 6.6 µg/L to 6.2 µg/L 1 hour after reaction). There was no infectious context or other confounding factors on the day of the challenge test.We inferred a drug-induced enterocolitis syndrome (DIES) caused by paracetamol, in the absence of other plausible causes. This child’s reaction met the various major and minor criteria described (3), independently of the dosage form, formally implicating paracetamol (Table 2). Therefore, the assay of specific immunoglobulins and the performance of a basophils activation test were not performed.Based on all these observations, we decided to propose an alternative treatment with ibuprofen, if the child had fever and eliminate cross allergy, confirmed by a negative challenge test. We will follow the child and perhaps propose another Paracetamol challenge test, in a few years, to assess possible cure of the syndrome. Since the provocation test, parents kept paracetamol excluded, the child no longer presented any digestive disorder. Prognosis of the DIES is actually unknown. Oral challenge seems to be indeed the only useful test to confirm or exclude DIES (3). In contrast, skin tests don’t provide conclusive evidence to diagnose DIES, as for FPIES.This is the first clinical presentation of DIES with paracetamol. Similar cases following antibiotic intakes (including amoxicillin) and only one for pantoprazole have been described, with similar clinical and biological manifestations (2). DIES is a clinical entity more frequent in a pediatric population, described with a minimum age of 2 years old, but adult cases are more and more reported in the literature. The patient is therefore younger than the cases described in the literature.Currently, it is considered in the literature that DIES is a syndrome equivalent to FPIES but with allergens of a different nature, respectively drug versus food. FPIES is a non-IgE mediated gastrointestinal food allergy (prevalence 1%), symptoms depend on the frequency of food exposure. FPIES affects infants and young children, diagnosis is clinical, and there are no specific biomarkers. In the literature, there were two kinds of FPIES being described: chronic FPIES occurs when food consumption is regular, symptoms (chronic diarrhea, vomiting, weight loss..) resolve with a period of avoidance, and acute FPIES occurs with occasional consumption of food and can have severe symptoms which may lead to shockSimilarly, DIES present specific criteria of non-IgE-mediated hypersensitivity, based only on the presence of typical symptoms (Table 2). However, to date, acute or chronic forms have not yet been described.Although its clinical manifestations can be severe and lead to hypovolemic shock, DIES pathophysiology is still not well understood. There is also no validated biomarker. According to Powell and al (4), neutrophilia has been recognized as a common finding in patients presenting with acute FPIES for a long time. The increase of the eosinophil cationic protein (ECP) in stool samples from 24 and 48 h after the reaction was also described. (5) Many cases of FPIES will be probably described in the coming years, maybe with new different drugs. This diagnosis should be considered in the event of a recurrent digestive disorder, at any age.To date, several unanswered questions need to be addressed. Clinicians must be known for example if DIES is a transient or persistent trouble. Further studies may allow to find the origin, evolution and treatment of DIES.In conclusion, we reported the first DIES induced by PARACETAMOL, with tolerance to IBUPROFEN, confirmed by oral challenge test. Until now, it is the youngest patient case report and the first for PARACETAMOL.Keywords: children; drug hypersensitivity reactions; drug-induced enterocolitis syndrome; drug allergy; antipyreticReferences1. Drug-Induced Enterocolitis Syndrome (DIES) Elio Novembre, Francesca Mori, Simona Barni, Neri Pucci,2. Mori F, Liccioli G, Fuchs O et al. Drug-induced enterocolitis syndrome: Similarities and differences compared with food protein-induced enterocolitis syndrome. Pediatr Allergy Immunol. 2021 Mar 2.3. Van Thuijl AOJ, Landzaat LJ, Liem O, et al. Drug-induced enterocolitis syndrome (DIES): A clinical entity that deserves more awareness. Ann Allergy Asthma Immunol. 2019 May;122(5):538-539.4. G K Powell. Enterocolitis in low-birth-weight infants associated with milk and soy protein intolerance J Pediatr. 1976 May;88(5):840-4.5. Freundt Serpa NP, Sánchez-Morillas L, Jaqueti Moreno P, González-Gutiérrez ML, Cimarra M, Cerecedo I, Fernández-Rivas M. Drug-Induced Enterocolitis Syndrome Due to Amoxicillin-Clavulanic Acid With Good Tolerance to Penicillin. J Investig Allergol Clin Immunol. 2020;30(4):301-302. doi: 10.18176/jiaci.0500. Epub 2020 Feb 25. PMID: 32101171.
Increased prevalence of Autoimmune Diseases in Children with Chronic Spontaneous UrticariaMichelle Le, MD1, Lydia Zhang MD2, Sofianne Gabrielli MSc2, Connor Prosty BSc, MD(c)1, Laura May Miles LLM, MD(c)2, Elena Netchiporouk, MD, MSc1, Sharon Baum, MD3, Shoshana Greenberger, MD3, Luis F. Ensina, MD, MSc, PhD4, Fatemeh Jafarian, MD1, Xun Zhang, PhD5, Moshe Ben-Shoshan, MD, MSc21Division of Dermatology, McGill University, Montreal, QC, Canada2Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada3Department of Dermatology, Chaim Sheba Medical Center, Tel-Aviv University, Sackler School of Medicine, Tel Hashomer, Israel4Department of Pediatrics, Federal University of São Paolo, Brazil5Centre for Outcome Research and Evaluation, Research Institute of McGill University Health Centre, Montreal, QC, CanadaCorrespondence: Michelle Le, M.D., 1001 Decarie Blvd, Montréal, Québec, H4A 3J1 email: [email protected] type: LetterManuscript word count: 981References : 10Tables : 1Figures: NoneFunding sources : NoneConflicts of interest: None declaredIRB Approval Status : Reviewed and approved by McGill University Health Centre; approval 12-255GEN
In conclusion, in a cohort of children with a history of severe bronchiolitis those exposed to ASM prenatally are not at increased risk of developing food or environmental allergen sensitization by early childhood. The mechanism by which ASM exposure increases risk of childhood asthma remains unclear, but alterations in the gut microbiome merit consideration.
Levetiracetam (LEV) is a second-generation antiepileptic drug (AED) that is well tolerated, has a broad spectrum of action, low protein binding, and minimal hepatic metabolism. The incidence of hypersensitivity to LEV in children and adults is 0.6%. This is the first reported fixed drug eruption (FDE) identified using a patch test in a pediatric case associated with LEV
Background: Defects in IFN–gamma receptor (IFN-γR) signaling via STAT1 leads to susceptibility to infection by otherwise weak pathogenic mycobacteria, resulting in mendelian susceptibility to mycobacterial disease. We identified three patients presented with disseminated mycobacterial infections caused by M. avium, M. persicum or M. bovis BCG respectively. Whole-exome sequencing (WES) was used as the first line diagnostic approach, however in all patients additional analysis was crucial to make the definite diagnosis. Method: WES, SNP array and long range PCR were performed to identify the genetic defects. Expression of IFNGR1, STAT1, CD64, SOCS1 and phosphorylation of STAT1 were determined after stimulation with IFN-α or IFN-γ. Results: In Patient 1, only one heterozygous variant p.(Val63Gly) in the IFNGR1 gene was identified by WES. Additional genetic analysis identified a second complex Alu-insertion in IFNGR1. Patient 2 was compound heterozygous for the null p.(Val68Lysfs*6) variant and the hypomorphic p.(Ile37Thr) variant in IFNGR1. In Patient 3 a novel variant in the STAT1 gene p.(Asn460Ile) was identified. Patients 1 and 2 had reduced expression of IFN-γR1. All patients had reduced phosphorylation of STAT1 and absent induction of SOCS1 after IFN-γ stimulation. While STAT1 phosphorylation was normal after IFN–α stimulation in Patient 1 and 2, and mildly reduced in Patient 3. Conclusion: We conclude that functional assays are crucial to assess the extent of IFN-γR signaling defects when new combinations of bi-allelic or non-conclusive genetic variants are found, which is important in the determination of clinical treatment.
Background: Guidelines for management of patients with allergic conditions are available, but the added value of nurses, allied health care professionals (AHPs) and general practitioners (GPs), in the management of allergic disease has not been fully clarified. The European Academy of Allergy and Clinical Immunology (EAACI) appointed a task force to explore this issue. Aim: To investigate the added value of nurses, AHPs and GPs in management of allergic diseases, in an integrated model of care. Methods: A search was made of peer-reviewed literature published between 2010 and December 2020 (Cochrane Library, PubMed, and CINAHL) on the involvement of the various specific health care providers (HCPs) in the management of allergic diseases. Results: Facilitative models of care for patients with allergies can be achieved if HCP collaborate in the diagnosis and management. Working in multidisciplinary teams (MDT) can increase patients’ understanding of the disease, adherence to treatment, self-care capabilities, and ultimately improve quality of life. The MDT competencies and procedures can be improved and enhanced in a climate of mutual respect and shared values, and with inclusion of patients in the planning of care. Patient-centered communication among HCPs and emphasis on the added value of each profession can create an effective integrated model of care for patients with allergic diseases. Conclusion: Nurses, AHPs, and GPs, both individually and in collaboration, can contribute to the improvement of the management of patients with allergic disease. The interaction between the HCPs and the patients themselves can ensure maximum support for people with allergies.