Eosinophilic pustular folliculitis (EPF) of infancy (EPFI), as a rare variant of EPF, is an inflammatory dermatosis characterized by recurrent outbreaks, itchy papulopustules and involvement of scalp and other body areas. In our case, we present a 3-month-old boy with persistent itchy vesiculopustular rashes on the scalp, hands and feet, eosinophilia in the peripheral blood test, widespread eosinophil clusters in the swab of the pustule and egg allergy in the skin prick test. This is the first case of EPFI associated with food allergy that is permanently suppressed by elimination diet with the limited use of cetirizine.

We report for the first time the case of allergy to egusi seeds in an atopic child of Nigerian origin with allergy to other seeds and nuts. This case highlights the need to know and explore less common foods as potential allergens, the importance of modified skin prick testing and the basophil activation test to support the diagnosis of rare food allergies and of awareness about world cuisine and exotic foods as potential allergens.

Background: Selective IgM deficiency (sIgMD), classified under primary immunodeficiencies, is characterized by low serum IgM(<2SD for age), normal IgG and IgA levels. The aim of this study was to define immunologic and clinical features of sIgMD. Method: We assessed a retrospective medical record of patients who fullfilled the criteria for sIgMD in a Pediatric Immunology department. Results: There were 55 patients with sIgMD. Out of 55 patients, thirteen(23.6%) diagnosed with a well-defined primary immunodeficiency (PID) during the follow-up.The ratio of the sIgMD was %0.12 in the out-patient clinic of pediatric immunology. Out of 33 patients, 8(23.5%) were asymtomatic during the follow-up period. Fifteen(45.4%) patients presented with several type of infections). Six patients (18%) had chromosomal anomaly, or syndrome (trisomy 21, 22q11.2 deletion 1p deletion, CHARGE syndrome, and Cohen Syndrome). Six (18%) had autoimmune/inflammatory diseases, such as Behcet’s disease, immune thrombocytopenic purpura, Crohn disease, Guillain Barre syndrome, and diabetes mellitus. Five(15%) had allergic disorders. Three(9%) have developed malignancy. The diagnoses of thirteen PID patients were combined immunodeficiency, common variable immunodeficiency, autoimmune lymphoproliferative syndrome, chronic granulomatous disease, adenosine deaminase deficiency, and congenital neutropenia. Genetic disorders, autoimmune/inflammatory and allergic diseases may accompany sIgMD. Approximately one third of the patients were asymptomatic in our series. Malignancy risk is relatively increased. We observed that an important ratio of patients with low IgM (23.6%) got sooner the diagnosis of a specific PID in the follow-up period. Conclusion: Thus, patients with sIgMD should be followed regularly in immunology clinics.

Postnatal SARS-CoV-2 Infection and Immunological Reaction: A Prospective Family Cohort Study

Background: Chronic spontaneous urticaria is well-described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria. Methods: This retrospective study followed children up to 18 years-old, diagnosed with chronic spontaneous urticaria, between the years 2002-2018 and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments and outcomes was extracted from electronic medical records. Results: Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4 years, 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25±15.2 months. The urticaria in 208 children )83.2%) resolved within 24 months. Eighty-seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2% and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease. Conclusions and clinical relevance: Chronic spontaneous urticaria in children is a self-limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population; increasing the possibility of a special subgroup of TH2-related chronic urticaria in children.

A document by Jana Eckert. Click on the document to view its contents.

BACKGROUND: Despite SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs, thus it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study seeks to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs samples. To define anti-SARS-CoV-2 antibodies we measured neutralization activity and total IgG load (Diasorin). We also evaluated antigen-specific B and CD8+T-cells, using a labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+T-cells. Whereas pro-inflammatory plasma protein profile was associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.

Comment on Platts-Mills T, Caraballo L, Jacquet A, Zarzuk J. Dust mite allergy. In: Dramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, et al. EAACI Molecular Allergology User’s Guide 2.0. Pediatr Allergy Immunol. 2023 Mar;34 Suppl. 28:e13854.

Background Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine assessment of household mitigation measures; nasopharyngeal, saliva and stool PCR testing; along with mucosal and systemic SARS-CoV-2 specific antibodies, to comprehensively characterise SARS-CoV-2 infection and transmission in households. Methods Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following onset of infection with ancestral SARS-CoV-2 variants. Results The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and non-respiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterised by lower respiratory Ct-values than low transmission families (Median 22.62 vs 32.91; IQR 17.06 to 28.67 vs 30.37 to 34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralising antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. Conclusion Utilising respiratory and non-respiratory PCR testing, along with measurement of SARS-CoV-2 specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.

Background: Periostin has emerged as a novel biomarker in the pathogenesis of T helper 2-type allergic diseases in the last years. The aim of this study was to investigate the association of serum periostin levels with clinical features in children with asthma. Methods: Children with physician-diagnosed asthma who attended regularly to an outpatient pediatric allergy and asthma center were enrolled in the study along with control subjects. Asthma severity and control status of the patients were evaluated according to recent GINA guidelines. Results: A total of 158 children (125 with asthma and 33 age and sex-matched control subjects) with a median age of 10.2 years (range 5.9-17.0) were enrolled. Asthma severity was mild in 41 (32.8%), moderate in 63 (50.4%) and severe in 21 (16.8%) children. Children with asthma had significantly higher periostin levels than controls (53.1 ± 13.1 vs 43.0 ± 11.2 ng/mL; p < 0.001). The mean serum periostin levels of children with severe asthma (63.8 ± 10.8) were significantly higher than in children with moderate asthma (53.3 ± 12.7) and mild asthma (47.4 ± 11.1) (p < 0.001). Serum periostin levels were found to be significantly correlated with asthma severity (Spearman’s rho [r]=0.41, p < 0.001). Results of multivariable logistic regression analysis demonstrated an association between serum periostin levels and asthma severity in children (OR, 1.10; 95% CI, 1.04-1.15; p <0.001) Conclusion: Serum periostin levels may serve clinicians in identifying children with severe asthma.

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect daily functioning of the infant and family, it is referred to GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and the medical and dietary management. The Task Force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using a predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.

Background: Due to the recency of the postbiotic field, there are no head-to-head postbiotic studies investigating its biotherapeutic potential for atopic dermatitis (AD). No network meta-analysis (NMA) has yet been conducted to synthesize relevant studies to compare postbiotic interventions for AD. Objective: To assess the comparative efficacy and safety of postbiotic strains for treating pediatric AD. Methodology: This is an NMA of randomized controlled studies that evaluate postbiotics in treating pediatric AD. Systematic search of databases and registers from inception to November 30, 2022. Three authors independently performed the search, screening, appraisal using the Cochrane risk of bias tool version 2 and data extraction. Data analysis was done using STATA14 software. Results: There were 9 studies that evaluated 8 postbiotic preparations. Lactobacillus rhamnosus IDCC 3201 (LR) ranked highest in the efficacy outcome. Compared to placebo, LR may be effective in reducing symptoms of atopic dermatitis both in the main analysis (SMD -0.53, 95%CI -1.02 to -0.04) and sensitivity analysis involving studies that used SCORAD (MD -5.52, 95% CI -10.46 to -0.58), based on low-certainty evidence. Based on moderate-certainty evidence, LR probably does not increase the risk of adverse events (RR 0.97, 95% CI 0.79 to 1.21). Although Lactobacillus paracasei GM080 (LP2) ranked highest in the safety outcome, it may not reduce AD symptoms compared to placebo (SMD -0.03, 95% CI -0.37 to 0.32) based on low-certainty evidence. Conclusion: LR showed significant benefits for children with AD, based on low-certainty evidence. Further investigation on LR is recommended.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately four weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

A document by Marguerite Lawler. Click on the document to view its contents.

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

Background: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. Methods: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients <18 years and initiating omalizumab between 2006-2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared to the baseline period. Results: Of the 484 patients included, 101 (20.9%) reached six years of treatment. The mean±standard deviation number of exacerbations decreased during the first year of treatment (7.9±6.6 to 1.1±2.0, p<0.001) and remained likewise for up to six years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. Conclusion: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long-term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited and spontaneously resolve within days after drug discontinuation, sometime HRs reactions to AEDs can be severe and life threatening. Aim: This paper seeks to show examples on practical management of AEDs HRs in children starting from a review of what it is already known in literature. Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications and genetic factors. The diagnosis work-up consists of in vivo (Intradermal testing and Patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays and granulysin (Grl) in flow cytometry]. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. Conclusion: Dealing with AEDs HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternate anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

We describe a case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) to multiple CFTR modulators and piperacillin in an 8 year old female with CF. To our knowledge this is the first reported case of delayed type, T-cell mediated hypersensitivity to multiple CFTR modulators described in literature. Our findings suggest possible cross-reactivity between CFTR modulators or multiple sensitisations, which should be taken into account in similar cases.