CD40 Ligand Deficiency in Latin America: Clinical, Immunological, and Genetic Characteristics.

CD40 ligand (CD40L) deficiency is a rare inborn error of immunity presenting with heterogeneous clinical manifestations. While a detailed characterization of patients affected by CD40L deficiency is essential to an accurate diagnosis and management, information about this disorder in Latin American patients is limited. We retrospectively analyzed data from 50 patients collected by the Latin American Society for Immunodeficiencies registry or provided by affiliated physicians to characterize the clinical, laboratory, and molecular features of Latin American patients with CD40L deficiency. The median age at disease onset and diagnosis was 7 months and 17 months, respectively, with a median diagnosis delay of 1 year. Forty-seven patients were genetically characterized revealing 6 novel mutations in the CD40LG gene. Pneumonia was the most common first symptom reported (66%). Initial immunoglobulin levels were variable among patients. Pneumonia (86%), upper respiratory tract infections (70%), neutropenia (70%), and gastrointestinal manifestations (60%) were the most prevalent clinical symptoms throughout life. Thirty-five infectious agents were reported, five of which were not previously described in CD40L deficient patients, representing the largest number of pathogens reported to date in a cohort of CD40L deficient patients. The characterization of the largest cohort of Latin American patients with CD40L deficiency adds novel insights to the recognition of this disorder, helping to fulfill unmet needs and gaps in the diagnosis and management of patients with CD40L deficiency.

Polyphasic characterisation of Burkholderia cepaciacomplex species isolated from children with cystic fibrosis.

Cystic fibrosis (CF) patients with Burkholderia cepacia complex (Bcc) pulmonary infections have high morbidity and mortality. The aim of this study was to compare different methods for identification of Bcc species isolated from paediatric CF patients. Oropharyngeal swabs from children with CF were used to obtain isolates of Bcc samples to evaluate six different tests for strain identification. Conventional (CPT) and automatised (APT) phenotypic tests, polymerase chain reaction (PCR)-recA, restriction fragment length polymorphism-recA, recA sequencing, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) were applied. Bacterial isolates were also tested for antimicrobial susceptibility. PCR-recA analysis showed that 36 out of the 54 isolates were Bcc. Kappa index data indicated almost perfect agreement between CPT and APT, CPT and PCR-recA, and APT and PCR-recA to identify Bcc, and MALDI-TOF and recA sequencing to identify Bcc species. The recA sequencing data and the MALDI-TOF data agreed in 97.2% of the isolates. Based on recA sequencing, the most common species identified were Burkholderia cenocepacia IIIA (33.4%),Burkholderia vietnamiensis (30.6%), B. cenocepaciaIIIB (27.8%), Burkholderia multivorans (5.5%), and B. cepacia (2.7%). MALDI-TOF proved to be a useful tool for identification of Bcc species obtained from CF patients, although it was not able to identify B. cenocepacia subtypes.

First report of the Hyper-IgM syndrome Registry of the Latin American Society for Immunodeficiencies: novel mutations, unique infections, and outcomes.

Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas.

Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis.

BACKGROUND: Patients with X-linked hyper-IgM syndrome (X-HIGM) due to CD40 ligand (CD40L) mutations are susceptible to fungal pathogens; however, the underlying susceptibility mechanisms remain poorly understood. OBJECTIVE: To determine whether monocyte-derived dendritic cells (DCs) from patients with X-HIGM exhibit normal responses to fungal pathogens. METHODS: DCs from patients and controls were evaluated for the expression of costimulatory (CD80 and CD86) and MHC class II molecules and for their ability to produce IL-12 and IL-10 in response to Candida albicans and Paracoccidioides brasiliensis. We also evaluated the ability of C albicans- and P brasiliensis-pulsed mature DCs to induce autologous T-cell proliferation, generation of T helper (T(H)) 17 cells, and production of IFN-γ, TGF-ß, IL-4, IL-5, and IL-17. RESULTS: Immature DCs from patients with X-HIGM showed reduced expression of CD80, CD86, and HLA-DR, which could be reversed by exogenous trimeric soluble CD40L. Most important, mature DCs from patients with X-HIGM differentiated by coculturing DCs with fungi secreted minimal amounts of IL-12 but substantial amounts of IL-10 compared with mature DCs from normal individuals. Coculture of mature DCs from X-HIGM patients with autologous T cells led to low IFN-γ production, whereas IL-4 and IL-5 production was increased. T-cell proliferation and IL-17 secretion were normal. Finally, in vitro incubation with soluble CD40L reversed the decreased IL-12 production and the skewed T(H)2 pattern response. CONCLUSION: Absence of CD40L during monocyte/DC differentiation leads to functional DC abnormalities, which may contribute to the susceptibility to fungal infections in patients with X-HIGM.

Are pediatricians familiar with hereditary angioedema?

Background: Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of subcutaneous or mucosal edema caused by excess bradykinin. The aim of the present study was to assess the knowledge of pediatricians about hereditary angioedema. Methods: An online survey with 12 HAE-related and 14 demographics-related questions was e-mailed to all pediatricians who were members of the Brazilian Society of Pediatrics (n = 17 145) once a week during the months of June and July 2021. The electronic questionnaire assessed clinical manifestations, diagnosis, and treatment of hereditary angioedema in children and adolescents. Results: Four hundred and fifty-five pediatricians responded to the questionnaire (2.6%), of whom 55 (12.1%) were board certified in Allergy and Immunology (A/I), while 400 (87.9%) were not (N-A/I). Three hundred and sixty-eight (80.9%) were female, 289 (55.7%) were under 50 years of age, 286 (62.9%) graduated from Medical School more than 10 years previously, 83 (18.2%) held an MSc/PhD degree, and 253 (55.6%) were living in the Southeast Region of Brazil. The median number of correct answers to the questions related to HAE among A/I was 7 out of 12 (58.3%), with median ranging from 4.5 to 8 correct answers, while for N-A/I it was 3 (25%), with median ranging from 2.5 to 4 correct answers (p < 0.001). Conclusion: Knowledge about HAE among Brazilian pediatricians, whether board certified in Allergy and Immunology or not, was unsatisfactory. HAE is a rare disease, largely unknown among physicians; therefore, increasing awareness may lead to improvement in diagnosis and treatment.

Expanding the clinical and genetic spectrum of human CD40L deficiency: the occurrence of paracoccidioidomycosis and other unusual infections in Brazilian patients.

CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T > G and c.476 G > C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.

Impact of the environment on the microbiome.

OBJECTIVES: This review aimed to verify indoor and outdoor pollution, host and environmental microbiome, and the impact on the health of the pediatric population. SOURCES: A review of the literature, non-systematic, with the search for articles since 2001 in PubMed with the terms "pollution" AND "microbiome" AND "children's health" AND "COVID-19". SUMMARY OF THE FINDINGS: Prevention of allergic diseases includes the following aspects: avoid cesarean delivery, the unnecessary overuse of antibiotics, air pollution, smoking in pregnancy and second-hand tobacco smoke, stimulate breastfeeding, soil connection, consume fresh fruits and vegetables, exercise and outdoor activities and animal contact. The children's microbiota richness and diversity decrease the risk of immune disbalance and allergic disease development. CONCLUSIONS: Lifestyle and exposure to pollutants, both biological and non-biological, modify the host and the environment microbiome provoking an immune disbalance with inflammatory consequences and development of allergic diseases.

Evaluation of corneal tomography in children and adolescents without ocular or systemic allergy.

PURPOSE: To determine normal corneal tomographic parameters in children and adolescents without corneal disease or atopy diagnosis. METHODS: This descriptive cross-sectional study evaluated patients aged 8-16 years who underwent a complete slit-lamp biomicroscopic examination and tomographic corneal evaluation by a dual Scheimpflug analyzer, excluding those with ocular disease (including allergic conjunctivitis) or a positive prick test for systemic atopies. RESULTS: A total of 170 patients were evaluated, and 34 patients (68 eyes) were analyzed once the exclusion criteria were applied. The sample's mean age was 10.76 ± 2.31 years; with 19 (55.9%) men and 15 (44.1%) women. The mean keratometry in the flat meridian (Kflat), steep meridian (Ksteep), and maximum (Kmax) were 42.37 ± 1.63D, 43.53 ± 1.65D, and 43.90 ± 1.73D, respectively. The mean values for corneal asphericity (ε2) and thinnest point were 0.28 ± 0.11 and 550.20 ± 37.90 µm, respectively. The inferior-superior asymmetry ratio (I-S) and coma were 0.74 ±0.59D and 0.28 ± 0.12D, respectively. CONCLUSION: The knowledge of normal corneal tomographic parameters and their variation in children and adolescents without corneal disease or atopy may be useful for diagnosing keratoconus and initiating early disease treatment.

Different Approaches to Atopic Dermatitis by Allergists, Dermatologists, and Pediatricians.

OBJECTIVES: Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease, with a vast drug arsenal and guidelines available for its management and diagnosis and different medical specialties engaged in providing care. This study aimed to outline the therapeutic and diagnostic approaches to the AD of allergists, dermatologists, and pediatricians and verify whether they are compliant with the guidelines. METHODS: A cross-sectional study using an electronic questionnaire administered through the SurveyMonkey® platform was disclosed by participating medical societies to their medical associates. RESULTS: Of the 1,473 participating physicians, the use of moisturizers as part of AD treatment was observed among pediatricians (91.9%), dermatologists (97.5%), and allergists (100%; p=0.07). The preference for the use of new emollients was lower among pediatricians (57%) than dermatologists (75.9%) and allergists (71.4%; p < 0.001). The prevalence of wet-wrap therapy was lower among dermatologists (16.3%) than allergists (51%; p < 0.001). The recommendation of proactive treatment with topical corticosteroids was more frequently reported by allergists (65.3%) than pediatricians (43.3%) and dermatologists (40.8%; p < 0.001), and the same trend was observed in relation to proactive treatment using calcineurin inhibitors. The use of oral anti-histamines to control pruritus was mainly considered by pediatricians (69.2%) and dermatologists (59.2% p < 0.001). Clinical experience with systemic immunomodulating agents was greater among allergists (77.5%) and dermatologists (60.8%; p < 0.001), with cyclosporine being the most cited systemic immunomodulating agent. Environmental control of aeroallergens was recommended by pediatricians (89.8%), dermatologists (86.9%), and allergists (100%; p=0.01). CONCLUSION: There were differences in the therapeutic and diagnostic approaches to AD used by allergists, dermatologists, and pediatricians and those recommended by the guidelines, especially regarding the use of wet-wrap therapy, proactive treatment with topical corticosteroids or calcineurin inhibitors, prescription of anti-histamines, recommendation of phototherapy, and control of aeroallergens.

Emergence of Thymidine-Dependent Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Patients in Southern Brazil.

We characterized Staphylococcus aureus small-colony variant (SCV) strains isolated from cystic fibrosis (CF) patients in southern Brazil. Smaller colonies of S. aureus were isolated from respiratory samples collected consecutively from 225 CF patients from July 2013 to November 2016. Two phenotypic methods-the auxotrophic classification and a modified method of antimicrobial susceptibility testing-were employed. PCR was conducted to detect the mecA, ermA, ermB, ermC, msrA, and msrB resistance genes. Furthermore, DNA sequencing was performed to determine the mutations in the thyA gene, and multilocus sequence typing was used to identify the genetic relatedness. S. aureus strains were isolated from 186 patients (82%); suggestive colonies of SCVs were obtained in 16 patients (8.6%). The clones CC1 (ST1, ST188, and ST2383), CC5 (ST5 and ST221), and ST398 were identified. Among SCVs, antimicrobial susceptibility testing showed that 77.7% of the isolates were resistant to multiple drugs, and all of them were susceptible to vancomycin. mecA (2), ermA (1), ermB (1), ermC (3), and msrB (18) were distributed among the isolates. Phenotypically thymidine-dependent isolates had different mutations in the thyA gene, and frameshift mutations were frequently observed. Of note, revertants showed nonconservative or conservative missense mutations. SCVs are rarely identified in routine laboratory tests. IMPORTANCE Similar findings have not yet been reported in Brazil, emphasizing the importance of monitoring small-colony variants (SCVs). Altogether, our results highlight the need to improve detection methods and review antimicrobial therapy protocols in cystic fibrosis (CF) patients.

Air pollution and indoor settings.

Indoor environments contribute significantly to total human exposure to air pollutants, as people spend most of their time indoors. Household air pollution (HAP) resulting from cooking with polluting ("dirty") fuels, which include coal, kerosene, and biomass (wood, charcoal, crop residues, and animal manure) is a global environmental health problem. Indoor pollutants are gases, particulates, toxins, and microorganisms among others, that can have an impact especially on the health of children and adults through a combination of different mechanisms on oxidative stress and gene activation, epigenetic, cellular, and immunological systems. Air pollution is a major risk factor and contributor to morbidity and mortality from major chronic diseases. Children are significantly affected by the impact of the environment due to biological immaturity, prenatal and postnatal lung development. Poor air quality has been related to an increased prevalence of clinical manifestations of allergic asthma and rhinitis. Health professionals should increase their role in managing the exposure of children and adults to air pollution with better methods of care, prevention, and collective action. Interventions to reduce household pollutants may promote health and can be achieved with education, community, and health professional involvement.

Current situation of allergy education in Mexico and other parts of Latin America.

Allergic diseases are one of the most frequent chronic diseases in the world. It has been established that there is a worldwide epidemic of allergic diseases; therefore, the treatment of allergies should be acknowledged as a worldwide priority and the specialty of allergy should be considered an important field in medicine. Due to the fact that allergic diseases involve many organs, and Allergy and Clinical Immunology is one of the specialties in which physicians may be trained to treat patients of all ages, the subject in medical schools is not always taught as an individual specialty but often as part of another subject such as internal medicine or pediatrics. Certified allergists are an important contribution to health systems, providing the necessary care for patients who have allergic diseases. Undergraduate programs in many universities do not include allergy as a subject, contributing to a lack of knowledge regarding the correct management of allergic diseases. World Health Organization (WHO) recommends 1 allergist per 50,000 people; however, there is an uneven distribution of allergy and clinical immunology specialists. Most practitioners are localized mainly in larger cities and state capitals, while in other regions, specialists are still greatly needed. Support and training systems are required for allergy and clinical immunology specialists to promote continuing education and keep their clinical competence up to date, which will lead to better care for their patients. Increased exposure to the concepts of allergy and clinical immunology diagnosis and treatment in undergraduate education may also potentially lead to an increase in interest in the field of allergy and clinical immunology among physicians in training. This review will approach allergy education in Mexico and other parts of Latin America.

Levels of Airborne Soybean Allergen (Gly m 1) in a Brazilian Soybean Production City: A Pilot Study.

Asthma epidemics have been shown to be related to where soybeans are loaded and handled, but data are scarce in the literature. This pilot study evaluated the levels of Gly m 1 in dust samples collected in Maringá, Brazil, a city with high soy production and processing. A dust impactor was used to collect seven isolated samples during 2015 and 2016. Samples were analyzed by an ELISA (enzyme-linked immunosorbent assay) detection method. Gly m 1 was found in all samples, ranging from 0.82-24.38 ng/m3 (median 2.41), regardless of the month or year evaluated. The levels of Gly m 1 were considered low, but the concentrations required to cause sensitization and symptoms are uncertain.

Endoscopic and histological characteristics in patients with eosinophilic esophagitis responsive and non-responsive to proton pump inhibitors.

OBJECTIVE: To compare endoscopic and histologic features of pediatric patients with eosinophilic esophagitis (EoE) responding to proton pump inhibitor (PPI) to those not responding to PPI. METHODS: Endoscopic reports and photographs of patients with symptoms of esophageal dysfunction and ≥15 eosinophils per high-powered field (eos/hpf) in esophageal biopsies prior to PPI trial were reviewed. Patients were classified as responsive to PPI (PPIREoE) or non-responsive to PPI (PPINREoE) according to response totreatment (<15 eos/hpf) at second endoscopy after 8 weeks. RESULTS: Of the 231 patients (72.3% male), 64 (27.7%) were responsive to the proton pump inhibitors. Edema (77.3% vs. 62.5%, p=0.031) and vertical lines (69.5% vs. 51.6%, p=0.014) were more frequent in PPINREoE patients. An eosinophil count in the mid-esophagus ≥ 35 eos/HPF (25.1% vs. 12.5%) was more frequent in these patients (p=0.001). Those with eosinophil count < 15 eos/HPF in the mid-esophagus at the first endoscopy were more likely to respond to treatment with proton pump inhibitors compared to patients with 15-34 eos/HPF (p=0.004, OR: 3.26, 95% CI: 1.46-7.24) and to patients with ≥ 35 eos/HPF (p=0.006, OR: 3.20, 95% CI: 1.39-7.41). CONCLUSION: Edema and vertical lines at the endoscopy and a higher eosinophil count in the mid-esophagus were more frequent in patients who were non-responsive to proton pump inhibitors. As there were no significant differences in the other findings between the groups, it cannot be affirmed that these characteristics are sufficient to differentiate between PPINREoE and PPIREoE patients.

Short-term Prophylaxis for Delivery in Pregnant Women with Hereditary Angioedema with Normal C1-Inhibitor.

OBJECTIVE: To verify the efficacy of short-term prophylaxis for vaginal or cesarean section childbirth with plasma-derived C1-inhibitor concentrate in pregnant women. They should have hereditary angioedema (HAE) and normal plasma C1-inhibitor. METHODS: Case report of pregnant women diagnosed with HAE with normal C1-inhibitor who had been treated with intravenous C1-inhibitor concentrate for prophylaxis of angioedema attacks when hospitalized for delivery. The exon 9 of the Factor 12 (F12) genotyping gene was performed by automatic sequencing in all patients. RESULTS: Three cases of pregnant women with HAE with normal serum level of C1-inhibitor are reported. The genetic test detected the presence of a pathogenic mutation in the F12 gene. Deliveries occurred uneventfully and patients had no HAE symptoms in the following 72 hours. CONCLUSION: C1-inhibitor concentrate could be useful to prevent angioedema attacks during and after delivery.

OBJETIVO: Verificar a eficácia da profilaxia de curto prazo para o parto vaginal ou cesáreo com inibidor de C1 derivado de plasma concentrado em mulheres grávidas. Eles devem ter angioedema hereditário e inibidor normal de C1 no plasma. MéTODOS: Relato de caso de gestantes diagnosticadas com angioedema hereditário com inibidor de C1 normal que foram tratadas com inibidor intravenoso de concentrado de C1 para profilaxia de ataques de angioedema quando hospitalizadas para o parto. O exon 9 do gene de genotipagem do fator 12 (F12) foi realizado por sequenciamento automático em todos os pacientes. RESULTADOS: Três casos de gestantes com angioedema hereditário com nível sérico normal de inibidor de C1 são relatados. O teste genético detectou a presença de uma mutação patogênica no gene F12. Os partos ocorreram sem intercorrências e as pacientes não apresentaram sintomas hereditários de angioedema nas 72 horas seguintes. CONCLUSãO: O concentrado de inibidor de C1 pode ser útil para prevenir ataques de angioedema durante e após o parto.

Evaluation of corneal tomography in children and adolescents without ocular or systemic allergy / Avaliação da tomografia de córnea em crianças e adolescentes sem alergia ocular ou sistêmica

ABSTRACT Purpose: To determine normal corneal tomographic parameters in children and adolescents without corneal disease or atopy diagnosis. Methods: This descriptive cross-sectional study evaluated patients aged 8-16 years who underwent a complete slit-lamp biomicroscopic examination and tomographic corneal evaluation by a dual Scheimpflug analyzer, excluding those with ocular disease (including allergic conjunctivitis) or a positive prick test for systemic atopies. Results: A total of 170 patients were evaluated, and 34 patients (68 eyes) were analyzed once the exclusion criteria were applied. The sample's mean age was 10.76 ± 2.31 years; with 19 (55.9%) men and 15 (44.1%) women. The mean keratometry in the flat meridian (Kflat), steep meridian (Ksteep), and maximum (Kmax) were 42.37 ± 1.63D, 43.53 ± 1.65D, and 43.90 ± 1.73D, respectively. The mean values for corneal asphericity (ε2) and thinnest point were 0.28 ± 0.11 and 550.20 ± 37.90 μm, respectively. The inferior-superior asymmetry ratio (I-S) and coma were 0.74 ±0.59D and 0.28 ± 0.12D, respectively. Conclusion: The knowledge of normal corneal tomographic parameters and their variation in children and adolescents without corneal disease or atopy may be useful for diagnosing keratoconus and initiating early disease treatment.

RESUMO Objetivo: Identificar parâmetros tomográficos de normalidade em córneas de crianças e adolescentes sem a presença de atopias sistêmicas e alergias oculares. Métodos: Este estudo descritivo transversal avaliou pacientes com idade entre 8 e 16 anos que foram submetidos a exame biomicroscópico completo por lâmpada de fenda e avaliação tomográfica da córnea por tomógrafo dual Scheimpflug, excluindo pacientes com doença ocular (incluindo conjuntivite alérgica) ou prick test positivo para atopias sistêmicas. Resultados: Cento e setenta pacientes foram avaliados e após cumpridos os critérios de exclusão, 34 (68 olhos) foram analisados. A média etária da amostra foi 10,76 ± 2,31 anos; 19 (55,9%) eram meninos e 15 (44,1%) meninas. A média da ceratometria em dioptrias (D) no meridiano mais plano (Kflat), mais curvo (Ksteep) e máxima (Kmax) foram 42,37 ± 1,63D, 43,53 ± 1,65D e 43,90 ± 1,73D, respectivamente. Os valores médios da asfericidade corneana (ε2) e do ponto mais fino da córnea foram 0,28 ± 0,11 e 550,20 ± 37,90 micras (μm). A assimetria corneana inferior-superior (I-S) e coma foi em média 0,74 ± 0,59D e 0,28 ± 0,12D, respectivamente. Conclusão: O conhecimento dos valores médios e sua variação de parâmetros tomográficos da córnea em crianças e adolescentes sem atopias sistêmicas ou alergias oculares pode ser útil para o diagnóstico precoce do ceratocone e o seu tratamento em estágio inicial.

Incidence of cystic fibrosis in five different states of Brazil as determined by screening of p.F508del, mutation at the CFTR gene in newborns and patients.

Cystic Fibrosis (CF) is one of the most common single-gene defects in European descent populations with an incidence of about 1 in every 2500 live births and carrier frequency of approximately 1 in 25. The most common mutation at the CF transmembrane conductance regulator (CFTR) gene is a deletion (p.F508del) of the phenylalanine codon 508; its frequency, however, is not the same throughout the world. The purpose of this paper is to document an application of a two-tier survey design in different states of Brazil, from which regional differences of the incidence of CF and frequency of CF-causing mutation(s) carriers can be for the first time estimated. We present data on genotype distributions in reference to p.F508del mutation in samples of newborns, adult controls and CF patients from five Brazilian states, in which a total of 2683 newborns born to Brazilian white parents and 500 African-Brazilians adult controls were screened, as well as 300 CF patients (262 European descents and 38 African descents) were genotyped. Our results suggest that the CF-incidence in different parts of Brazil may differ by almost 20-fold. For the five different states as a whole, nearly 48% of the CF-alleles carry the p.F508del mutation, which places the estimates of disease incidence and carrier frequencies for the Brazilian European descents as 1 in 7576 live births and 2.3%, respectively. The implications for prevention of CF and other rare Mendelian diseases through such surveys of mutation screening are discussed.

Oral food challenge in children with contact urticaria in reaction to cow’s milk

Objective: To evaluate the relationship between the occurrence of contact urticaria in reaction to cow’s milk in infants and the diagnosis of cow’s milk allergy (CMA) established by supervised oral food challenge. Methods: In this cross-sectional study, we identified 184 children who had undergone 221 oral food challenge (OFC) at a CMA reference center between July 2015 and August 2019. Of these, 23 (12.5%) had a history of contact urticaria to cow’s milk and underwent a total of 30 OFC. Baked cow’s milk OFC were excluded, and 21 children were included in the study. All data from clinical history and allergy tests (serum-specific IgE dosages and skin prick test [SPT] with reconstituted cow’s milk formula) were recorded on standardized forms. The challenge was conducted with reconstituted cow’s milk formula in increasing volumes every 15–20 min. Results: 24 OFC were performed; 13/24 (54.2%) for diagnostic purpose and 11/24 (45.8%) to evaluate cow’s milk tolerance. Allergy tests were positive in 14 patients (87.5%). Positive oral challenge outcomes were identified in 7/24. One patient had a late flare of atopic dermatitis and five children presented with immediate urticaria (two generalized urticaria and three perioral urticaria). The median papule diameter was 6.5 mm in patients with a positive OFC and 3.75 mm in the negative group (P = 0.02). Conclusion: The occurrence of contact urticaria might be the only manifestation among infants sensitized to cow’s milk with tolerance to oral ingestion. Reactions due to oral challenge were related to a larger wheal diameter on the SPT (AU)

Risco de exacerbação de asma em adolescentes usuários de dispositivos eletrônicos de liberação de nicotina: uma revisão sistemática e metanálise / Risk of asthma exacerbation in adolescent users of electronic nicotine delivery systems: a systematic review and meta-analysis

Este trabalho tem como objetivo investigar a associação entreo o uso dos cigarros eletrônicos e doenças pulmonares em adolescentes. Foi realizada uma revisão sistemática na base de dados PubMed. Os termos Mesh incluídos na busca foram "Electronic Nicotine Delivery Systems" e "Lung Diseases" e sinônimos no título e abstract, com o filtro de idade "child: birth - 18 years", para buscar artigos relacionados ao uso de cigarros eletrônicos e doenças pulmonares em adolescentes. Os critérios de elegibilidade consistiram em: usuários adolescentes, exposição ao cigarro eletrônico e doença pulmonar como desfecho. Os artigos foram selecionados por uma revisão pareada de maneira independente, primeiramente com a leitura dos títulos e resumos, seguida da leitura integral dos artigos selecionados, os quais foram analisados pela ferramenta New Castle-Ottawa quanto sua qualidade, e receberam entre 5 e 7 estrelas. Os dados encontrados foram extraídos para a realização da metanálise. Inicialmente foram encontrados 61 artigos, sendo seis considerados elegíveis, todos transversais e com aplicação de questionários. Na metanálise foi encontrada uma associação significativa entre o uso de cigarro eletrônico e exacerbação de asma (OR ajustado 1,44; IC 95% 1,17­1,76). Não foram encontrados estudos que avaliassem a associação do cigarro eletrônico e outras doenças pulmonares, incluindo EVALI (E-cigarette or Vaping product use-Associated Lung Injury), em adolescentes. Na metanálise foi encontrada uma associação significativa entre exacerbações de asma e uso de cigarros eletrônicos em adolescentes com asma crônica e nos previamente hígidos.

This study aims to investigate the association between electronic cigarette use and lung disease in adolescents. A systematic review was conducted in PubMed. We used the MeSH terms "Electronic Nicotine Delivery Systems" and "Lung Diseases" as well as synonyms in the title and abstract, with the age filter "child: birth - 18 years" to search for articles related to electronic cigarette use and lung disease in adolescents. The eligibility criteria consisted of adolescent users and exposure to e-cigarettes that resulted in lung disease. The articles were selected by independent assessment, reading first the titles and abstracts, then the full text of the selected articles. The Newcastle-Ottawa Scale was used to assess study quality, and the included studies received between 5 and 7 stars. Finally, the data were extracted for meta-analysis. Initially, 61 articles were found and 6 were considered eligible, all of which were cross-sectional and applied questionnaires. The meta-analysis found a significant association between electronic cigarette use and asthma exacerbation (adjusted OR 1.44 95% CI 1.17 - 1.76). However, no studies evaluated the association with other lung diseases, including electronic cigarette or vaping product use-associated lung injury in adolescents. The metaanalysis revealed a significant association between e-cigarette use and asthma exacerbation among adolescents with chronic asthma, as well as among their previously healthy peers.