Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study.

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

TEMPORAL COMPARISON OF WHEEZING PREVALENCE IN THE FIRST YEAR OF LIFE IN SÃO PAULO: INTERNATIONAL STUDY OF WHEEZING IN INFANTS. / COMPARAÇÃO TEMPORAL DA PREVALÊNCIA DE SIBILÂNCIA NO PRIMEIRO ANO DE VIDA EM SÃO PAULO: ESTUDO INTERNACIONAL DE SIBILÂNCIA EM LACTENTES.

OBJECTIVE: To assess the prevalence and severity of wheezing in the first year of life of infants, using the standardized protocol of the Estudio Internacional de Sibilancias en Lactantes- phase 3, and compare the values obtained with those found in phase 1, conducted at the same center. METHODS: Between 2009 and 2010, parents and guardians of infants answered the written questionnaire of the Estudio Internacional de Sibilancias en Lactantes - phase 3, and its results were compared to those of phase 1, performed between 2005 and 2006. We divided the infants into wheezing and non-wheezing. The wheezing group was stratified according to the frequency of episodes: occasional wheezing - less than three -, and recurrent wheezing - three or more. RESULTS: Wheezing prevalence was similar in both phases (44.6 versus 46%). Regarding frequency, the prevalence of occasional wheezing increased (19.4 versus 23%; p=0.03) and recurrent wheezing decreased (26.7 versus 21.6%; p=0.005). Also, diagnosis of asthma (7.5 versus 21.8%), use of inhaled corticosteroids (11.7 versus35%), and hospitalization for wheezing (19.7 versus 32.6%) grew significantly in phase 3. This period coincides with the Influenza A (H1N1) pandemic, which could have contributed to this outcome. CONCLUSIONS: Wheezing prevalence in the first year of life remains high. Despite the temporal assessment showing a decrease in the prevalence of recurrent wheezing, a significant increase in its morbidity was identified due to the higher number of hospitalizations. In addition, there were signs of improvement in the wheezing management of infants, reflected by an increase in the diagnosis of asthma and a greater indication of preventive treatments.

OBJETIVO: Avaliar a prevalência e a gravidade da sibilância em lactentes no primeiro ano de vida, utilizando o protocolo padronizado do Estudio Internacional de Sibilancias en Lactantes- fase 3, e comparar os valores obtidos com os observados no Estudio Internacional de Sibilancias en Lactantes- fase 1, realizado no mesmo centro. MÉTODOS: Entre 2009 e 2010, pais e responsáveis de lactentes responderam ao questionário escrito do Estudio Internacional de Sibilancias en Lactantes- fase 3, e os resultados obtidos foram comparados aos do Estudio Internacional de Sibilancias en Lactantes- fase 1, realizado entre 2005 e 2006. Oslactentes foram separados em sibilantes e "não sibilantes". Osprimeiros foram divididos de acordo com a frequência dos episódios: sibilância ocasional, quando apresentaram menos de três, e sibilância recorrente, quando manifestaram três ou mais. RESULTADOS: A prevalência de sibilantes foi similar nas duas fases (44,6 versus46%). Segundo a frequência, houve aumento na prevalência de sibilância ocasional (19,4 versus 23%; p=0,03) e redução na de sibilância recorrente (26,7 versus 21,6%; p=0,005). Observou-se, ainda, aumento expressivo no diagnóstico de asma (7,5 versus 21,8%) e no uso de corticosteroides inalatórios (11,7 versus 35%), como também na hospitalização por sibilância na fase 3 (19,7 versus 32,6%), período da pandemia Influenza A (H1N1), o que pode ter contribuído para este desfecho. CONCLUSÕES: A prevalência da sibilância no primeiro ano de vida permanece elevada. Apesar de a avaliação temporal mostrar queda na prevalência da sibilância recorrente, aumento significante de sua morbidade foi identificado pelo maior número de hospitalizações. Além disso, houve indícios de melhora no manejo da sibilância dos lactentes, refletido pelo aumento do diagnóstico de asma e maior indicação de tratamentos preventivos.

Comparação temporal da prevalência de sibilância no primeiro ano de vida em são paulo: estudo internacional de sibilância em lactentes / Temporal comparison of wheezing prevalence in the first year of life in são paulo: international study of wheezing in infants

RESUMO Objetivo: Avaliar a prevalência e a gravidade da sibilância em lactentes no primeiro ano de vida, utilizando o protocolo padronizado do Estudio Internacional de Sibilancias en Lactantes- fase 3, e comparar os valores obtidos com os observados no Estudio Internacional de Sibilancias en Lactantes- fase 1, realizado no mesmo centro. Métodos: Entre 2009 e 2010, pais e responsáveis de lactentes responderam ao questionário escrito do Estudio Internacional de Sibilancias en Lactantes- fase 3, e os resultados obtidos foram comparados aos do Estudio Internacional de Sibilancias en Lactantes- fase 1, realizado entre 2005 e 2006. Oslactentes foram separados em sibilantes e "não sibilantes". Osprimeiros foram divididos de acordo com a frequência dos episódios: sibilância ocasional, quando apresentaram menos de três, e sibilância recorrente, quando manifestaram três ou mais. Resultados: A prevalência de sibilantes foi similar nas duas fases (44,6 versus46%). Segundo a frequência, houve aumento na prevalência de sibilância ocasional (19,4 versus 23%; p=0,03) e redução na de sibilância recorrente (26,7 versus 21,6%; p=0,005). Observou-se, ainda, aumento expressivo no diagnóstico de asma (7,5 versus 21,8%) e no uso de corticosteroides inalatórios (11,7 versus 35%), como também na hospitalização por sibilância na fase 3 (19,7 versus 32,6%), período da pandemia Influenza A (H1N1), o que pode ter contribuído para este desfecho. Conclusões: A prevalência da sibilância no primeiro ano de vida permanece elevada. Apesar de a avaliação temporal mostrar queda na prevalência da sibilância recorrente, aumento significante de sua morbidade foi identificado pelo maior número de hospitalizações. Além disso, houve indícios de melhora no manejo da sibilância dos lactentes, refletido pelo aumento do diagnóstico de asma e maior indicação de tratamentos preventivos.

ABSTRACT Objective: To assess the prevalence and severity of wheezing in the first year of life of infants, using the standardized protocol of the Estudio Internacional de Sibilancias en Lactantes- phase 3, and compare the values obtained with those found in phase 1, conducted at the same center. Methods: Between 2009 and 2010, parents and guardians of infants answered the written questionnaire of the Estudio Internacional de Sibilancias en Lactantes - phase 3, and its results were compared to those of phase 1, performed between 2005 and 2006. We divided the infants into wheezing and non-wheezing. The wheezing group was stratified according to the frequency of episodes: occasional wheezing - less than three -, and recurrent wheezing - three or more. Results: Wheezing prevalence was similar in both phases (44.6 versus 46%). Regarding frequency, the prevalence of occasional wheezing increased (19.4 versus 23%; p=0.03) and recurrent wheezing decreased (26.7 versus 21.6%; p=0.005). Also, diagnosis of asthma (7.5 versus 21.8%), use of inhaled corticosteroids (11.7 versus35%), and hospitalization for wheezing (19.7 versus 32.6%) grew significantly in phase 3. This period coincides with the Influenza A (H1N1) pandemic, which could have contributed to this outcome. Conclusions: Wheezing prevalence in the first year of life remains high. Despite the temporal assessment showing a decrease in the prevalence of recurrent wheezing, a significant increase in its morbidity was identified due to the higher number of hospitalizations. In addition, there were signs of improvement in the wheezing management of infants, reflected by an increase in the diagnosis of asthma and a greater indication of preventive treatments.

Correction to: Chronic Granulomatous Disease in a Brazilian Patient Mimetizing Sarcoidosis.

The original version of abstract PO-162 "Chronic Granulomatous Disease in a Brazilian Patient Mimetizing Sarcoidosis" incorrectly listed the name of the second author as Micheli Barsioti. The correct spelling of the author's name is Michele Baziotti Man.

Conhecimento médico sobre as imunodeficiências primárias na cidade de São Paulo, Brasil / Medical awareness concerning primary immunodeficiency diseases in the city of São Paulo, Brazil

OBJETIVO: Avaliar o conhecimento médico sobre as imunodeficiências primárias na cidade de São Paulo (SP). MÉTODOS: Um questionário de 14 questões sobre as imunodeficiências primárias foi aplicado a médicos que trabalhavam em hospitais gerais. Uma das questões apresentava 25 situações clínicas que poderiam ou não estar associadas às imunodeficiências primárias, e a porcentagem de respostas apropriadas gerou um indicador de conhecimento. RESULTADOS: Participaram do estudo 746 médicos, dentre os quais 215 pediatras (28,8%), 244 cirurgiões (32,7%) e 287 clínicos (38,5%). Cerca de 70% dos médicos responderam ter aprendido sobre as imunodeficiências primárias na graduação ou na residência médica. O atendimento a pacientes que usam antibióticos com frequência foi relatado por 75% dos médicos, mas apenas 34,1% já haviam investigado algum paciente e 77,8% não conheciam os dez sinais de alerta para as imunodeficiências primárias. O indicador de conhecimento obtido apresentou uma média de 45,72% (±17,87). Apenas 26,6% dos pediatras e 6,6% tanto dos clínicos quanto dos cirurgiões apresentaram indicador de conhecimento de pelo menos 67% (equivalente à resposta apropriada em dois terços das situações clínicas). CONCLUSÃO: Há uma deficiência no conhecimento médico das imunodeficiências primárias na cidade de São Paulo, mesmo entre os pediatras, a despeito do maior contato com o tema nos últimos anos. A melhora da informação sobre as imunodeficiências primárias entre a comunidade médica é um importante passo para o diagnóstico e o tratamento precoces dessas doenças.

OBJECTIVE: To evaluate medical knowledge of primary immunodeficiency in the city of São Paulo (SP). METHODS: A 14-item questionnaire about primary immunodeficiency was applied to physicians who worked at general hospitals. One of the questions presented 25 clinical situations that could be associated or not with primary immunodeficiency, and the percentage of appropriate answers generated a knowledge indicator. RESULTS: Seven hundred and forty-six participated in the study, among them 215 pediatricians (28.8%), 244 surgeons (32.7%), and 287 clinicians (38.5%). About 70% of the physicians responded that they had learned about primary immunodeficiency in graduate school or in residency training. Treatment of patients that use antibiotics frequently was reported by 75% dos physicians, but only 34.1% had already investigated a patient and 77.8% said they did not know the ten warning signs for primary immunodeficiency. The knowledge indicator obtained showed a mean of 45.72% (±17.87). Only 26.6% if the pediatricians and 6.6% of clinicians and surgeons showed a knowledge indicator of at least 67% (equivalent to an appropriate answer in two thirds of the clinical situations). CONCLUSION: There is a deficit in medical knowledge of primary immunodeficiency in the city of São Paulo, even among pediatricians, despite having greater contact with the theme over the last few years. The improvement of information on primary immunodeficiency in the medical community is an important step towards the diagnosis and treatment process of these diseases.

Primary Immunodeficiency May Be Misdiagnosed as Cow's Milk Allergy: Seven Cases Referred to a Tertiary Pediatric Hospital.

Introduction. The presence of eczema and gastrointestinal manifestations are often observed in cow's milk allergy (CMA) and also in some primary immunodeficiency diseases (PID). Objective. To describe 7 patients referred to a tertiary allergy/immunology Center with a proposed diagnosis of CMA, who were ultimately diagnosed with PID. Methods. This was a retrospective study based on clinical and laboratory data from medical records. Results. Seven patients (6 males) aged between 3 mo and 6 y were referred to our clinic with a proposed diagnosis of CMA. They presented with eczema and/or gastrointestinal symptoms. Five were receiving replacement formula. All patients presented with other clinical features, including severe/recurrent infections unrelated to CMA, and two of them had a positive family history of PID. Laboratory tests showed immune system dysfunctions in all patients. Hyper-IgE and Wiskott-Aldrich syndromes, CD40L deficiency, severe combined immunodeficiency, X-linked agammaglobulinemia, transient hypogammaglobulinemia of infancy, and chronic granulomatous disease were diagnosed in these children. In conclusion, allergic diseases and immunodeficiency are a result of a different spectrum of abnormalities in the immune system and may be misdiagnosed. Educational programs on PID among clinical physicians and pediatricians can reduce the occurrence of this misdiagnosis.

Medical awareness concerning primary immunodeficiency diseases in the city of São Paulo, Brazil.

OBJECTIVE: To evaluate medical knowledge of primary immunodeficiency in the city of São Paulo (SP). METHODS: A 14-item questionnaire about primary immunodeficiency was applied to physicians who worked at general hospitals. One of the questions presented 25 clinical situations that could be associated or not with primary immunodeficiency, and the percentage of appropriate answers generated a knowledge indicator. RESULTS: Seven hundred and forty-six participated in the study, among them 215 pediatricians (28.8%), 244 surgeons (32.7%), and 287 clinicians (38.5%). About 70% of the physicians responded that they had learned about primary immunodeficiency in graduate school or in residency training. Treatment of patients that use antibiotics frequently was reported by 75% dos physicians, but only 34.1% had already investigated a patient and 77.8% said they did not know the ten warning signs for primary immunodeficiency. The knowledge indicator obtained showed a mean of 45.72% (±17.87). Only 26.6% if the pediatricians and 6.6% of clinicians and surgeons showed a knowledge indicator of at least 67% (equivalent to an appropriate answer in two thirds of the clinical situations). CONCLUSION: There is a deficit in medical knowledge of primary immunodeficiency in the city of São Paulo, even among pediatricians, despite having greater contact with the theme over the last few years. The improvement of information on primary immunodeficiency in the medical community is an important step towards the diagnosis and treatment process of these diseases.

Imunodeficiencia combinada severa: descricao de caso clinico / Severe combined immunodeficiency: description of clinical case

A imunodeficiencia combinada severa e uma doenca rara, cuja heranca e autossomica recessiva ou ligada ao cromossomo X. As manifestacoes clinicas expressam um defeito na resposta antigeno especifica. Os autores apresentam a avaliacao de uma crianca portadora de SCID, que apresentava processos infeciosos recorrentes, com multiplas internacoes. Foi realizada a avaliacao imunologica e descartada a deficiencia de adenosina-deaminase. O paciente foi submetido a herniorrafia de urgencia, evoluindo para obito no setimo dia pos-operatorio. O preparo para possivel transplante de medula ossea havia sido iniciado. Os achados anatomo-patologicos mostraram alteracoes em todo sistema imunologico. E discutida a importancia do diagnostico clinico e terapeutico precoces.

Imunodeficiencia combinada severa / Severe combined immnodeficiency

As imunodeficiencias primarias (ID) sao classificadas em ID humorais, celulares, combinadas (humorais e combinadas), de fagocitos e complemento. A Sindrome de Imunodeficiencia Combinada Severa discutida na presente monografia, e uma doenca rara com comprometimento da imunidade celular e humoral, cuja heranca e auto-somica recessiva ou ligada ao cromossomo X. Sao varios os defeitos descritos que levam a SCID: bloqueio das "stem cells", bloqueio da maturacao das celulas T e anormalidades da membrana celular. As principais manifestacoes clinicas sao os processos infecciosos recorrentes associados alteracoes cutaneas, pulmonares, de trato digestivo, com evolucao grave (meningite, sepsis). Os exames laboratoriais mostram linfopenia (20 por cento), niveis de imonuglobulinas baixos e ausencia de resposta linfoproliferativa "in vitro". A terapeutica de reposicao de imunoglobulinas esta indicada e a correcao definitiva pode ser obtida atraves do transplante de medula ossea ou terapia genica (na deficiencia de Adenosina Deaminase)