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Autoimmune manifestations in SCID due to IL7R mutations: Omenn syndrome and cytopenias

B+NK+SCID (severe combined immunodeficiency) due to IL7Rα deficiency represents approximately 10% of American SCID cases. To better understand the spectrum of autoimmune disorders associated with IL7Rα deficiency, we describe two unrelated IL7Rα-deficient female SCID infants whose clinical picture was dominated by autoimmune manifestations: one with intrauterine Omenn syndrome (OS) and another with persistent thrombocytopenic purpura since 4months of age. The OS baby harbored a homozygous p.C118Y mutation in IL7R. She presented dense eosinophilic infiltrates in several organs, including pancarditis, which may have contributed to her death (on the 2nd day of life). B cells were observed in lymph nodes, spleen, bone marrow and thymus. The second patient harbored compound heterozygous p.C118Y and p.I121NfsX8 mutations. She underwent a successful unrelated cord blood transplant. In conclusion, early OS can be observed in patients with IL7R mutations, and autoimmune cytopenias could also complicate the clinical course of SCID babies with this type of defect.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies

RESUMO Nos ultimos anos, novas imunodeficiencias primarias e defeitos geneticos tem sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composicao e para uso por via subcutânea, tornaram-se disponiveis em nosso meio. Com o objetivo de orientar o medico no uso da imunoglobulina humana para o tratamento das imunodeficiencias primarias, os membros do Grupo de Assessoria em Imunodeficiencias da Associacao Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisao narrativa da literatura e sua [...]

Baked milk tolerant patient: Is there any special feature?

BACKGROUND Determining whether patients with cows milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. OBJECTIVES The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. MATERIALS AND METHODS A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8g of cows milk protein). To exclude cows milk (CM) tolerance, the patients were subsequently challenged with unheated CM. RESULTS Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin (p=0.01) and casein (p=0.004) and the serum specific IgE for casein (p=0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p=0.037). CONCLUSIONS Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance.

The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers

Autoimmune polyendocrine syndrome type 1 (APS1) is characterized by multiorgan autoimmunity. We aim at characterizing a multi-center Brazilian cohort of APS1 patients by clinical evaluation, searching mutation in the AIRE gene, measuring serum autoantibodies, and investigating correlations between findings. We recruited patients based on the clinical criteria and tested them for AIRE mutations, antibodies against interferon type I and interleukins 17A, 17F and 22. We identified 12 unrelated families (13 patients) with typical signs of APS1 in the proband, and the screening of relatives recognized an asymptomatic child. Candidiasis was present in all cases, and 19 other manifestations were observed. All patients carried one of 10 different mutations in AIRE, being 3 new ones, and were positive for anti-interferon type I serum antibody. Anti-interleukin-17A levels inversely correlated with the number of manifestations in each patient. This negative correlation may suggest a protective effect of anti-interleukin-17A with a potential therapeutic application.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies (vol 15, pg 1, 2017)

[This corrects the article doi: 10.1590/S1679-45082017AE3844].

Comment to: II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies. einstein (Sao Paulo). 2017; 15(1): 1-16

Caro editor, Em relação ao “II Consenso Brasileiro sobre o uso de imunoglobulina humana em pacientes com imunodeficiências primárias”, publicado na revista einstein (São Paulo), em 2017, volume 15, numero 1,(1) gostaríamos de atualizar uma informação fornecida na página 6, a respeito do uso de imunoglobulina subcutânea facilitada pela hia luronidase. No momento da redação do texto, a informação, devidamente referenciada, era de que o produto não se encontrava aprovado em crianças e gestantes, mesmo nos países em que estava disponível comercialmente. No entanto, o produto está liberado na Europa para uso em crianças de qualquer idade desde julho de 2016.(2-4) O uso em gestantes ainda se encontra em investigação.(4) Consideramos relevante corrigir esta informação de maneira a garantir que o texto por nós redigido forneça as informações mais atualizadas possível, ao mesmo tempo que garantimos que os pacientes tenham acesso a mais este recurso terapêutico, assim que esta medicação seja liberada para uso em nosso meio.

Esofagite eosinofílica: um conceito em evolução?

RESUMO 1. Instituto da Criança Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Unidade de Alergia e Imunologia São Paulo, SP, Brasil. 363 O objetivo deste artigo é revisar a literatura dos últimos 10 anos sobre esofagite eosinofílica (EoE) e descrever os conceitos atuais da doença em seus aspectos de definição, fisiopatologia, fatores de risco, quadro clínico, diagnóstico e tratamento. Foram pesquisados artigos na base de dados do PubMed, do Bireme/ LILACS e do SciELO, nos últimos 10 anos. Os critérios para a inclusão dos artigos foram: (a) publicação nos últimos 10 anos, (b) artigos originais, (c) apenas humanos, (d) artigos de revisão, (e) diretrizes. Os critérios de exclusão foram: (a) artigos que não continham como tema principal a EoE, (b) artigos repetidos, (c) descrição de casos, (d) artigos com abordagem muito específicas para tratamento e diagnóstico. Foi realizada leitura dos resumos por dois pesquisadores, e posterior seleção dos artigos completos para a leitura. Foram acrescentados estudos que aprofundavam aspectos cruciais da revisão, sendo incluídos, ao todo, 3 consensos, 35 estudos e 3 artigos de revisão, que constituíram o total de artigos analisados. A conclusão é de que a EoE é uma doença crônica, cujos aspectos clínicos são fundamentais para a suspeita diagnóstica, mas requer a associação de achados endoscópicos e histológicos para sua confirmação. Na última década, houve modificações significativas nos critérios diagnósticos e algumas novas recomendações no tratamento, mas que necessitam uma observação em longo prazo. Descritores: Esofagite eosinofílica, diagnóstico, patologia, tratamento farmacológico. The objective of this paper was to review literature on eosinophilic esophagitis (EoE) published over the last 10 years and to describe current disease concepts related to definition, pathophysiology, risk factors, clinical presentation, diagnosis and treatment. We searched the PubMed, Bireme/LILACS and SciELO databases for articles published in the last 10 years. The following inclusion criteria were used to select articles: (a) publication in the last 10 years; (b) original articles; (c) studies with humans only; (d) review articles; (e) guidelines. Exclusion criteria were: (a) articles that did not have EoE as the main subject; (b) repeated articles; (c) case reports; (d) articles addressing a very specific treatment or diagnostic technique. Abstracts were screened by two investigators, and articles meeting the criteria were selected for full-text reading. Any relevant studies addressing crucial aspects of the review were added to the sample, resulting in a total of 3 consensus articles, 35 original articles, and 3 review articles. The review showed that EoE is a chronic disease in which clinical aspects are essential for diagnostic suspicion, but associated endoscopic and histological findings are required to confirm diagnosis. Over the last 10 years, significant changes were observed in diagnostic criteria, and some new treatment recommendations emerged, however still requiring long-term follow-up.

Cow's milk allergy: Evaluating tolerance through skin-prick test.

Objective: To evaluate the wheal diameter in allergy skin-prick tests (SPT) with cows milk extract (CM) comparing tolerant and persistent patients. Method: A retrospective cohort study involving database analysis of children with diagnosis of cows milk protein allergy (CMPA) mediated by immunoglobulin E in a specialized outpatient clinic that regularly performed SPT between January 2000 and July 2015. Patients were allocated into two groups: tolerant or persistent. Comparisons were made at diagnosis and over time between tolerant and persistent patients using Fishers, Mann-Whitney or Wilcoxon tests and significance level at 5%. Results: After applying inclusion and exclusion criteria, the sample includes 44 patients (29 tolerant and 15 who persisted with CMPA). In the tolerant group, the medians of SPT were: 6 mm at diagnosis and 2 mm at the development of tolerance; a significant difference (p<0.0001) was found. In the persistent group, the median SPT at diagnosis was 7 mm, while in the last SPT it was 5 mm, with no statistical difference (p=0.173). The comparison of medians in the last SPT between groups was significant (p=0.001), with a reduction greater than 50% in SPT in the tolerant group. Conclusion: Serial SPTs were useful for diagnosis, and a decrease higher than 50% in diameter can indicate the moment to perform oral food challenge (OFC) tests, helping to detect tolerance in CMPA.

Primary hypogammaglobulinemia: The impact of early diagnosis in lung complications

Objective: To describe clinical features, tomographic findings and pulmonary function in pediatric patients with primary hypogammaglobulinemia (PH). Method: A retrospective cohort study of children with PH who received intravenous immunoglobulin (IVIG) and prophylactic antibiotics between 2005 and 2010. Epidemiological and clinical features, computed tomography (CT) findings, and spirometric data were compared, assuming a 5% significance level. Results: We evaluated 30 patients with PH. After the start of IVIG replacement, there was a decline in the frequency of pneumonia (p<0.001). The 11 patients with bronchiectasis in their first CT scan were older at diagnosis (p=0.001) and had greater diagnostic delay (p=0.001) compared to patients without bronchiectasis. At the end of the study, 18 patients had bronchiectasis and 27 also had other lung disorders, alone or in combination. The Bhalla score was applied to the last CT scan of 16 patients, with a median score of 11 (range 7-21), with a positive correlation between the score and the number of pneumonias after the start of treatment (r=0.561; p=0.024). The score was also correlated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) values in 13/16 patients, with negative correlation to FEV1 previously to bronchodilator (r=-0.778; p=0.002) and after bronchodilator (r =-0.837; p<0.001) and FVC (r=-0.773; p=0.002). Conclusion: Pulmonary complications were common in this cohort, despite the decrease in the frequency of pneumonia with treatment. Early investigation of patients with recurrent infections for primary immunodeficiencies can reduce the frequency of these complications. The monitoring of changes in spirometry may indicate the need to carry out radiological investigation.

Hemophagocytic lymphohistiocytosis: contribution from clinical and laboratory criteria for the diagnosis

Results Eight patients (4 males) were evaluated, being diagnosed 2 mutations in the perforin gene (in 3 patients, including twins), 3 secondary to Chediak-Higashi syndrome, 1 associated to Epstein-Baar virus infection, 1 associated to Kawasaki syndrome, and another unknown cause. The median age at diagnosis was 29,5 months (from 2 months to 12 years). The median time necessary to confirm HLH was 21 days (from 15 to 42 days), and the most precocious ones were in patients with genetic mutations. Fever was the first symptom presented by all patients, the incidence of thrombocytopenia was also 100%; anemia, hypertriglyceridemia and increased ferritin were presented by 87%; hypofibrinogenemia by 75%; neutropenia and splenomegaly by 62%; hemophagocytosis in bone marrow by 37%. The most frequent criteria combination was fever, thrombocytopenia, anemia, increased ferritin and hypertriglyceridemia. Soluble CD25 and NK-cell activity weren’t avaiable at the diagnosis. By the time HLH was established, all patients were receiving antibiotics. Their outcomes were 2 deaths, 2 bone marrow transplants with good evolution and 4 patients are still in follow-up.