Vitamin D supplementation and severity of atopic dermatitis: pre-post assessment.

BACKGROUND/OBJECTIVES: There is evidence that vitamin D (VD) supplementation may help in the management of atopic dermatitis (AD). The aim of this study was to assess the influence of VD supplementation on the severity of AD. METHODS: Pre-post interventional study with prospective data collection in patients younger than 14 years. The severity of AD was determined through SCORAD (SCORing Atopic Dermatitis) and classified as mild (SCORAD < 25), moderate (≥25 and <50), and severe (≥50). Skin prick test was performed in all patients. Serum VD levels were classified as sufficient (≥30 ng/mL), insufficient (29 to 21 ng/mL), and deficient (≤20 ng/mL); and those with inadequate levels received oral supplementation of VD for 3 months, and were reassessed after treatment. RESULTS: A total of 152 patients were included. Patients with sufficient vitamin levels had lower SCORAD values (p = 0.04). Further, 116 patients (76.3%) received VD supplementation and after 3 months, VD levels were significantly higher (35.9 ng/mL) compared to baseline levels (23.7 ng/mL, p < 0.001). At the same time, a reduction in the SCORAD index was observed (19.4 before vs 12.3 after supplementation, p < 0.001). Considering other factors that could influence the decrease in AD severity after VD supplementation, female gender was associated with a worse treatment response (p = 0.02). CONCLUSION: Vitamin D supplementation could be an adjuvant in reducing the severity of atopic dermatitis.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2).

INTRODUCTION: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. PATIENTS AND METHODS: This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. RESULTS: Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. CONCLUSION: The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Ocular symptoms in nonspecific conjunctival hyperreactivity.

BACKGROUND: Ocular symptoms can be triggered by nonspecific environmental factors, characterizing conjunctival hyperreactivity (CHR). OBJECTIVE: To examine CHR in subjects with ocular symptoms by means of a hyperosmolar conjunctival provocation test (HCPT). METHODS: Sixty-three subjects with ocular complaints (itching, redness, or tearing) were tested for allergy to a common panel of inhalant allergens (Alk Abelló-FDA Allergenic, Brazil). They were considered allergic if tests were positive to at least 1 allergen. HCPT with serial diluted glucose concentrations was positive if it produced conjunctival hyperemia up to a 50% solution. Digital images were analyzed by 2 observers who marked redness in the challenged eyes in red (GIMP 2.6.5 software). The number of red dots of the affected eye was compared with the number of blue dots of the control eye. RESULTS: HCPT was positive in 6 of 7 grass pollen-sensitive subjects, in 17 of 20 dust mite-sensitive subjects, and in 10 of 11 subjects who were sensitive to both allergens. HCPT was positive in 33 of 38 allergic subjects (87%) and in 4 of 25 (16%) non-allergic subjects; sensitivity was 87%, and specificity was 84%. Significant correlation (r = 0.96 Pearson; P < .0001) was seen between the number of red dots in 23 digitalized images marked by observers. CONCLUSION: HCPT indentified CHR in allergic as well as in non-allergic subjects. Allergic subjects exhibited more CHR than did non-allergic subjects. Conjunctival hyperreactivity was present in allergic subjects even when they were asymptomatic. Digital images may be useful for objective evaluation of ocular hyperemia in HCPT.

Conjunctival Provocation Test With Blomia tropicalis.

Background: Conjunctival provocation test (CPT) is used to demonstrate clinical relevance to a specific allergen. Blomia tropicalis (Bt) is a prevalent allergen in tropical regions. Its major allergen Blo t 5 is commonly detected in house dust in Brazil. Patients with allergic rhinoconjunctivitis (ARC) have IgE antibodies to Bt although it may not indicate clinical allergy. Objective: The purpose of this study is to demonstrate the role of CPT in clinical allergy to Bt in allergic conjunctivitis (AC). Methods: CPT was performed in asymptomatic subjects with ARC (n = 26) outside the grass pollen season. They had positive skin prick tests (SPT) to Bt and other common inhalant allergens and they were off topical or systemic antihistamines. Standardized allergens were used for CPT (Blo t 5 462.5 ng/mL in 1:1 solution, Alk Abelló). CPT was conducted on a control group of subjects (n = 29) without symptoms of ARC and with negative SPT. CPT was performed with progressive doses of allergen solutions in normal saline (1:32, 1:16, 1:8, 1:4, 1:2). CPT with the same allergen dose that elicited a positive reaction was repeated one week later. The protocol was approved by the local Ethics Board and signed informed consent was obtained from all participants. Results: There were 92% (24/26) of positive CPT in subjects sensitized to Bt. Significant association was found between SPT and CPT results with Bt (p < 0.0001). CPT had 92% sensitivity and 100% specificity when compared to SPT results. Positive reactions with the same dose or one immediately higher occurred in 21 out of 22 subjects who repeated TPC 1 week later. Mild transient nasal symptoms (21/24) were the major side effects of positive CPT followed by moderate periorbital edema which occurred in 41% (10/24). One controlled asthmatic BT-sensitized subject developed wheezing and dyspnea during a positive CPT with Bt that cleared with inhaled albuterol (400 mcg). There were no reactions whatsoever of CPT in non-allergic subjects. Conclusion: This study demonstrated that Bt may cause allergic conjunctivitis in our population. In addition, CPT is a safe and reproducible test if standardized allergens are used.

Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis.

Allergic rhinitis (AR) is the most common undiagnosed chronic condition in children. Moderate/severe AR symptoms significantly impair quality of life, and cause sleep disruption, absenteeism and decreased productivity. Additionally, untreated AR predisposes children to asthma and other chronic conditions. Although intranasal corticosteroids are the most effective pharmacologic treatment for AR, oral antihistamines are often preferred. First-generation antihistamines may be chosen to relieve AR symptoms as they are inexpensive and widely available; however, they cause sedative and cardiovascular negative effects due to poor receptor selectivity. Therefore, second-generation antihistamines were developed to reduce adverse effects while retaining efficacy. There are fewer clinical trials in children than adults, therefore, efficacy and safety data is limited, particularly in children under 6 years, highlighting the need to generate these data in young children with AR. Fexofenadine, a highly selective second-generation antihistamine, effectively alleviates symptoms of AR, is non-sedating due to decreased blood-brain barrier permeability, and is devoid of cardiovascular side effects. Importantly, fexofenadine relieves the ocular symptoms of allergic conjunctivitis, which occur concomitantly with AR, improving quality of life. Overall, fexofenadine displays a favorable safety profile and results in greater treatment satisfaction in children compared with other second-generation antihistamines. This review aimed to evaluate and compare the safety and efficacy of fexofenadine with other available first- and second-generation antihistamines in children with AR.

Associated factors with recurrent wheezing in infants: is there difference between the sexes?

OBJECTIVE: Identify associated factors for recurrent wheezing (RW) in male and female infants. METHODS: Cross-sectional multicentric study using the standardized questionnaire from the Estudio Internacional sobre Sibilancias en Lactantes (EISL). The questionnaire was applied to parents of 9345 infants aged 12-15 months at the time of immunization/routine visits. RESULTS: One thousand two hundred and sixty-one (13.5%) males and nine hundred sixty-three (10.3%) females have had RW (≥3 episodes), respectively (p10 colds episodes (OR = 3.46; IC 95% 2.35-5.07), air pollution (OR = 1.33; IC 95% 1.12-1.59), molds at home (OR = 1.23; IC 95% 1.03-1.47), Afro-descendants (OR = 1.42; IC 95% 1.20-1.69), bronchopneumonia (OR = 1.41; IC; 1.11-1.78), severe episodes of wheezing in the first year (OR = 1.56; IC 95% 1.29-1.89), treatment with bronchodilators (OR = 1.60; IC 95% 1.22-2,1) and treatment with oral corticosteroids (OR = 1,23; IC 95% 0.99-1,52). Associated factors for RW for females were passive smoking (OR = 1.24; IC 95% 1.01-1,51), parents diagnosed with asthma (OR = 1.32; IC 95% 1,08-1,62), parents with allergic rhinitis (OR = 1.26; IC 95% 1.04-1.53), daycare attendance (OR = 1.48; IC 95% 1.17-1,88), colds in the first 6 months of life (OR = 2.19; IC 95% 1.69-2.82), personal diagnosis of asthma (OR = 1.84; IC 95% 1.39-2.44), emergency room visits (OR = 1.78; IC 95% 1.44-2.21), nighttime symptoms (OR = 2.89; IC 95% 2.34-3.53) and updated immunization (OR = 0.62; IC 95% 0.41-0.96). CONCLUSION: There are differences in associated factors for RW between genders. Identification of these differences could be useful to the approach and management of RW between boys and girls.

VITAMIN D RECEPTOR GENE MUTATIONS AND VITAMIN D SERUM LEVELS IN ASTHMATIC CHILDREN. / MUTAÇÕES DO GENE DO RECEPTOR DE VITAMINA D E NÍVEIS SÉRICOS DE VITAMINA D EM CRIANÇAS COM ASMA.

OBJECTIVE: To verify the relationship between polymorphisms of the vitamin D receptor gene (VDR), clinical findings, and serum vitamin D (VD) levels in asthmatics. METHODS: A cross sectional study of 77 children aged 7 to 14 years old, who were attended at a specialized clinic. The children were divided into 3 groups: asthmatics who had been using inhaled corticosteroids (ICS) for more than one year; asthmatics who had not been using ICS; non-asthmatics, and children without allergies (according to the International Study of Asthma and Allergies in Childhood -- ISAAC). Spirometry, skin prick tests, the presence of a VDR promoter CDX2 polymorphism from an allele-specific polimerase chain reaction (PCR), exons 2 and 3 polymorphisms genotyping by PCR-SSCA (single-strand conformational analysis), total immunoglobulin E (IgE) and specific IgE to mites and grass were evaluated in these three groups. Levels of 25-hydroxyvitamin D were determined in asthmatics only. RESULTS: The mean age of the children was 10.8±2.0 years old, 57% were male, 38 were asthmatic and using ICS, 22 were asthmatic and not using ICS, and 17 were non-asthmatic. Allergic rhinitis was present in 90% of asthmatics. Homozygous CDX2 was detected in 23% of the patients and absent in the control group (p=0.03). Lower forced expiratory volume in 1 second (FEV1%) values were observed in CDX2 homozygous asthmatics (p=0.001). Variations in the exon 2 and 3 sequences were not related to asthma or the other tests. VD deficiency or insufficiency was detected in 98% of asthmatics. There was no association between VD levels and genetic polymorphisms from exons 2 and 3. CONCLUSIONS: There was a positive association between homozygous CDX2 polymorphism, asthma and lower FEV1% values. CDX2 is capable of modifying cell interaction between VDR and VD, and it could be associated with the prevalence of asthma, and the difficulty in controlling the disease.

OBJETIVO: Verificar a relação dos polimorfismos do gene do receptor de vitamina D (RVD) com sinais clínicos e níveis de vitamina D (VD) em asmáticos. MÉTODOS: Estudo transversal com 77 crianças de 7 a 14 anos de um ambulatório especializado, divididas em 3 grupos: asmáticos, em uso de corticoide inalatório (ICS) por mais de um ano; asmáticos sem necessidade de ICS; não asmáticos e não alérgicos (de acordo com o International Study of Asthma and Allergies in Childhood - ISAAC. Foram avaliados: espirometria, testes alérgicos, presença do polimorfismo CDX2 do promotor do RVD por reação em cadeia da polimerase (PCR) e genotipagem de polimorfismos dos éxons 2 e 3 por PCR-SSCA (single-strand conformational analysis), imunoglobulina E (IgE) total e IgE específica para ácaros e gramíneas nos três grupos estudados. Níveis de 25-hidroxivitamina D foram dosados nos asmáticos. RESULTADOS: A média de idade foi 10,8±2,2 anos, 57% masculinos, 38 asmáticos com ICS, 22 sem ICS e 17 não asmáticos. Rinite alérgica esteve presente em 90% dos asmáticos, polimorfismo CDX2 em 23% dos asmáticos e ausente nos controles (p=0,03). Menores níveis de volume expiratório forçado no primeiro segundo (VEF1%) foram observados nos asmáticos homozigotos para CDX2 (p=0,001). Variações nas sequências dos éxons 2 e 3 não foram relacionadas com a asma ou demais testes. Deficiência ou insuficiência de VD foi diagnosticada em 98% dos asmáticos. Não houve associação entre níveis de VD e polimorfismos genéticos dos éxons 2 e 3. CONCLUSÕES: Observou-se associação positiva entre polimorfismo CDX2 em homozigoze com asma e menores valores de VEF1%. O CDX2 pode modificar a interação celular do RVD com a vitamina, bem como pode estar associado com a asma e com a dificuldade de controle da doença.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Prevalence of recurrent wheezing in infants.

OBJECTIVE: To identify the prevalence of recurrent wheezing in infants in the city of Curitiba, PR, Brazil. METHODS: A cross-sectional study carried out by means of administering questionnaires to the parents of infants aged 12 to 15 months attending health centers for immunization during the period between August 2005 and December 2006. This is a standardized and validated instrument consisting of questions on demographic characteristics, wheezing, respiratory infections and risk factors. At the time of the study the City Health Department had 107 health centers, 35 of which were selected by lots and distributed homogeneously across the municipal territory. RESULTS: A total of 1,364 infants (45.4%) had episodes of wheezing during their first 12 months of life, with onset at 5.5+/-3.1 months (mean +/- standard deviation), and 678 (22.6%) had had three or more episodes. In 84.6% of the wheezing children treatment was with .2-agonists, with inhaled corticosteroids in 18.5%, oral corticosteroids in 24.3% and leukotriene receptor antagonists were used with 5.4%. The wheezing children exhibited nocturnal symptoms, intense difficulty breathing and visits to emergency services in the proportions of 58.9, 46.2 and 57.6%, respectively; 12.7% were admitted to hospital for asthma and 10.9% had had a medical diagnosis of asthma. Nocturnal symptoms, visits to emergency, severity of symptoms, hospital admissions for asthma and medical diagnoses of asthma were all more common among those who had suffered three or more crises (p < 0.001). CONCLUSIONS: There is an elevated prevalence of wheezing among the infants of Curitiba, with early onset and elevated morbidity. It is possible that these infants represent a large contingent of asthmatics.

Mudanças na sazonalidade de polens de Poaceae em Curitiba / Seasonal changes in Poaceae pollen counts in Curitiba, south of Brazil

Introdução: Doenças alérgicas afetam de 10 a 30% da população mundial, e polens são frequentes desencadeantes. A polinose é doença decorrente da sensibilização ao pólen e é a forma sazonal da rinite alérgica e/ou asma mediada pela imunoglobulina E (IgE). A família Poaceae tem o maior número de gêneros de plantas que contribuem para a polinose, pois liberam alta quantidade de pólen na atmosfera e são largamente distribuídas. Objetivo: O presente trabalho quantificou a concentração de polens da família Poaceae na atmosfera de Curitiba e comparou a curva de distribuição de polens com os dados das décadas de 1980 e 90. Também classificou a concentração diária de pólen de gramíneas segundo a National Allergy Bureau (NAB). Método: O equipamento de amostragem foi o captador volumétrico Hirst, instalado a uma altura de aproximadamente 25 metros. Resultados: O pico de concentração diária de pólen total ocorreu no começo do mês de agosto, correspondendo a 302 grãos/m3. O mês de agosto também concentrou oito dos maiores picos diários de pólen total, sendo sete deles superiores a 200 grãos/m3. Foi encontrado pólen Poaceae ao longo de todo o ano e o maior pico de concentração foi de 27 grãos/m3 em agosto e setembro. Nas décadas de 80 e 90, os picos de polens foram no mês de novembro e período de polinização entre outubro e abril. Isso não foi observado no ano de 2018, uma vez que a época de polinização das gramíneas se adiantou, com início em agosto, e o pico de concentração foi em de agosto e setembro. Conclusão: Este estudo mostra que houve mudança na estação polínica. Os dois picos de dispersão de polens de Poaceae se repetem ao longo dos anos, mas têm sido encontrados em outros meses. Pacientes com alergia a polens podem ter sintomas por exposição fora das estações determinadas anteriormente.

Background: Allergic diseases affect 10% to 30% of the world population, with pollen as a major trigger. Pollinosis results from sensitization to pollen and is the seasonal form of allergic rhinitis and/or immunoglobulin E (IgE)-mediated allergic asthma. The Poaceae family is distributed worldwide and has the largest number of plant genera contributing to pollinosis, as they release large amounts of pollen into the atmosphere. Objective: To quantify pollen grains from the Poaceae family in the atmosphere of Curitiba, compare the pollen distribution curve with data from the 1980s and 1990s, and classify the daily concentration of grass pollen according to the National Allergy Bureau (NAB). Method: A Hirst-type volumetric sampler was placed at approximately 25 meters from the ground. Results: The peak of daily total pollen concentration occurred in early August, corresponding to 302 grains/m3. August also had 8 of the highest daily total pollen concentrations, 7 of which were greater than 200 grains/m3. Poaceae pollen was found throughout the year, with the highest concentration peak of 27 grains/m3 in August and September. In the 1980s and 1990s, the pollen peaks occurred in November and the pollen season occurred between October and April. In 2018, however, the pollen season started earlier, in August, and the pollen peaks occurred in August and September. Conclusion: This study shows a change in the grass pollen season. Although the 2 peaks of Poaceae pollen dispersion have repeated over the years, grass pollen is currently observed in other months of the year. Patients with pollen allergy may experience symptoms from allergen exposure outside the previously established grass pollen seasons.

Diretriz Latino-americana sobre o Diagnóstico e Tratamento da Alergia Ocular ­ Em nome da Sociedade Latinoamericana de Alergia, Asma e Imunologia (SLAAI) / Latin American Guideline on the Diagnosis and Treatment of Ocular Allergy ­ On behalf of the Latin American Society of Allergy, Asthma and Immunology (SLAAI)

A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.

Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.

Associated factors with recurrent wheezing in infants: is there difference between the sexes?

Abstract Objective: Identify associated factors for recurrent wheezing (RW) in male and female infants. Methods: Cross-sectional multicentric study using the standardized questionnaire from the Estudio Internacional sobre Sibilancias en Lactantes (EISL). The questionnaire was applied to parents of 9345 infants aged 12-15 months at the time of immunization/routine visits. Results: One thousand two hundred and sixty-one (13.5%) males and nine hundred sixty-three (10.3%) females have had RW (≥3 episodes), respectively (p10 colds episodes (OR = 3.46; IC 95% 2.35-5.07), air pollution (OR = 1.33; IC 95% 1.12-1.59), molds at home (OR = 1.23; IC 95% 1.03-1.47), Afro-descendants (OR = 1.42; IC 95% 1.20-1.69), bronchopneumonia (OR = 1.41; IC; 1.11-1.78), severe episodes of wheezing in the first year (OR = 1.56; IC 95% 1.29-1.89), treatment with bronchodilators (OR = 1.60; IC 95% 1.22-2,1) and treatment with oral corticosteroids (OR = 1,23; IC 95% 0.99-1,52). Associated factors for RW for females were passive smoking (OR = 1.24; IC 95% 1.01-1,51), parents diagnosed with asthma (OR = 1.32; IC 95% 1,08-1,62), parents with allergic rhinitis (OR = 1.26; IC 95% 1.04-1.53), daycare attendance (OR = 1.48; IC 95% 1.17-1,88), colds in the first 6 months of life (OR = 2.19; IC 95% 1.69-2.82), personal diagnosis of asthma (OR = 1.84; IC 95% 1.39-2.44), emergency room visits (OR = 1.78; IC 95% 1.44-2.21), nighttime symptoms (OR = 2.89; IC 95% 2.34-3.53) and updated immunization (OR = 0.62; IC 95% 0.41-0.96). Conclusion: There are differences in associated factors for RW between genders. Identification of these differences could be useful to the approach and management of RW between boys and girls.