Chronic polyarthritis as isolated manifestation of toxocariasis.

Human toxocariasis is a parasitic zoonosis mainly caused by Toxocara canis or Toxocara cati and is acquired by ingestion of the parasite's embryonated eggs. Arthralgia and/or arthritis were reported in up to 17% of the cases, generally with acute duration (less than 6 weeks). However, to our knowledge, chronic polyarthritis, as the isolated presentation of Toxocara infection, was not reported. One of the 5809 patients that was followed up at our service (0.017%) had chronic polyarthritis as the single manifestation of toxocariasis and was described herein. A 3-year-old girl was referred to our service with severe painful chronic polyarthritis for a period longer than 10 weeks and morning stiffness of 30min. Dog contact exposure history in the recreational areas of neighborhood was reported. Her exams showed high levels of eosinophils in peripheral blood (29%), bone marrow aspirate revealed marked eosinophilia (32%) and Toxocara enzyme-linked immunosorbent assay (Elisa) was positive (1:1280). She was treated with paracetamol (40mg/kg/day) and thiabendazole (25mg/kg/day) for 10 days, and all manifestations reduced. After eight months of follow-up, she was on clinical and laboratorial remission. In conclusion, we described a case of chronic polyarthritis, as isolated manifestation of toxocariasis, mimicking juvenile idiopathic arthritis and leukemia. Importantly, this zoonosis should be considered in patients with arthritis and eosinophilia.

Chronic polyarthritis as isolated manifestation of toxocariasis / Poliartrite crônica como manifestação isolada da toxocaríase

ABSTRACT Human toxocariasis is a parasitic zoonosis mainly caused by Toxocara canis or Toxocara catiand is acquired by ingestion of the parasite’s embryonated eggs. Arthralgia and/or arthri-tis were reported in up to 17% of the cases, generally with acute duration (less than 6weeks). However, to our knowledge, chronic polyarthritis, as the isolated presentation ofToxocara infection, was not reported. One of the 5809 patients that was followed up at ourservice (0.017%) had chronic polyarthritis as the single manifestation of toxocariasis and wasdescribed herein. A 3-year-old girl was referred to our service with severe painful chronicpolyarthritis for a period longer than 10 weeks and morning stiffness of 30 min. Dog contactexposure history in the recreational areas of neighborhood was reported. Her exams showedhigh levels of eosinophils in peripheral blood (29%), bone marrow aspirate revealed markedeosinophilia (32%) and Toxocara enzyme-linked immunosorbent assay (Elisa) was positive(1:1280). She was treated with paracetamol (40 mg/kg/day) and thiabendazole (25 mg/kg/day)for 10 days, and all manifestations reduced. After eight months of follow-up, she was onclinical and laboratorial remission. In conclusion, we described a case of chronic polyarthri-tis, as isolated manifestation of toxocariasis, mimicking juvenile idiopathic arthritis andleukemia. Importantly, this zoonosis should be considered in patients with arthritis andeosinophilia.

RESUMO A toxocaríase é uma zoonose parasitária causada principalmente pelo Toxocara canis ou peloT. cati. É adquirida pela ingestão de ovos embrionados do parasita. A artralgia e/ou artriteforam relatadas em até 17% dos casos, geralmente com duração aguda (menos de seis sema-nas). No entanto, que se tem conhecimento, a poliartrite crônica como manifestação isoladada infecção por Toxocara ainda não foi descrita na literatura. Um dos 5.809 pacientes acom-panhados em nosso serviço (0,017%) exibiu poliartrite crônica como manifestação únicada toxocaríase e foi descrito neste estudo. Uma menina de três anos foi encaminhada aonosso serviço com poliartrite crônica dolorosa grave por um período superior a 10 semanase rigidez matinal diária de 30 minutos. Foi relatada história de exposição a contato comcão nas áreas de lazer do bairro. Seus exames revelaram níveis elevados de eosinófilos nosangue periférico (29%), o aspirado de medula óssea revelou eosinofilia acentuada (32%)e o ensaio imunoenzimático ligado a enzima (ELISA) para Toxocara foi positivo (1:1.280). Acriança foi tratada com paracetamol (40 mg/kg/dia) e tiabendazol (25 mg/kg/dia) durante10 dias e houve regressão de todas as manifestações. Depois de oito meses de seguimento,a pequena paciente estava em remissão clínica e laboratorial. Em conclusão, descreve-seum caso de poliartrite crônica como manifestação isolada da toxocaríase, que mimetizouuma artrite idiopática juvenil e leucemia. É importante ressaltar que essa zoonose deve serconsiderada em pacientes com artrite e eosinofilia.

Doenças autoimunes e autoanticorpos em pacientes pediátricos e seus parentes de primeiro grau com deficiência de imunoglobulina / Autoimmune diseases and autoantibodies in pediatric patients and their first-degree relatives with immunoglobulin A deficiency

Introdução: As manifestações clínicas da deficiência de imunoglobulina A (DIgA) incluem infecções recorrentes, atopia e doenças autoimunes. No entanto, para o nosso conhecimento, as avaliações concomitantes de doenças autoimunes e autoanticorpos em uma coorte de pacientes com DIgA com idade atual > 10 anos e seus parentes não foram feitas. Objetivos: Avaliar doenças autoimunes e presença de autoanticorpos em pacientes com DIgA e seus parentes de primeiro grau. Métodos: Estudo transversal feito em 34 pacientes com DIgA (idade atual > 10 anos) e em seus parentes de primeiro grau. Todos foram acompanhados em um centro terciário brasileiro para imunodeficiência primária: 27 crianças/adolescentes e sete de seus parentes de primeiro grau com diagnóstico tardio de DIgA. Doenças autoimunes e autoanticorpos (anticorpos antinucleares, fator reumatoide e antitireoglobulina, antitiroperoxidase e anticorpos antiendomísio da classe IgA) também foram avaliadas. Resultados: Doenças autoimunes (n = 14) e/ou autoanticorpos (n = 10, quatro deles com autoanticorpos isolados) foram observadas em 18/34 (53%) dos pacientes e seus parentes. As doenças autoimunes mais comuns encontradas foram tireoidite (18%), artrite crônica (12%) e doença celíaca (6%). Os autoanticorpos mais frequentes foram anticorpos antinucleares (2%), antitireoglobulina e/ou antitireoperoxidase (24%). Nenhuma diferença significativa foi observada no sexo feminino, idade no momento do diagnóstico e idade atual em pacientes com DIgA com e sem doenças autoimunes e/ou presença de autoanticorpos (p > 0,05). As frequências de imunodeficiência de primárias na família, autoimunidade em família, atopia e infecções recorrentes foram semelhantes em ambos os grupos (p> 0,05). Conclusão: Doenças autoimunes e autoanticorpos foram observadas em pacientes com DIgA durante o acompanhamento, o que reforça a necessidade de um acompanhamento rigoroso e contínuo durante a adolescência e a idade adulta. .

Introduction: Clinical manifestations of Immunoglobulin A Deficiency (IgAD) include recur-rent infections, atopy and autoimmune diseases. However, to our knowledge, theconcomitant evaluations of autoimmune diseases and auto antibodies in a cohort of IgADpatients with current age >10 years and their relatives have not been assessed. Objectives: To evaluate autoimmune diseases and the presence of auto antibodies in IgADpatients and their first-degree relatives. Methods: A cross-sectional study was performed in 34 IgAD patients (current age >10years) and their first-degree relatives. All of them were followed at a tertiary Brazilianprimary immunodeficiency center: 27 children/adolescents and 7 of their first-degree rela-tives with a late diagnosis of IgAD. Autoimmune diseases and autoantibodies (antinuclearantibodies, rheumatoid factor, and anti-thyroglobulin, anti-thyroperoxidase and IgA classanti-endomysial antibodies) were also assessed. Results: Autoimmune diseases (n = 14) and/or autoantibodies (n = 10, four of them with iso-lated autoantibodies) were observed in 18/34 (53%) of the patients and their relatives. Themost common autoimmune diseases found were thyroiditis (18%), chronic arthritis (12%)and celiac disease (6%). The most frequent autoantibodies were antinuclear antibodies(2%), anti-thyroglobulin and/or anti-thyroperoxidase (24%). No significant differences wereobserved in the female gender, age at diagnosis and current age in IgAD patients with andwithout autoimmune diseases and/or presence of auto antibodies (p > 0.05). The frequen-cies of primary immunodeficiencies in family, autoimmunity in family, atopy and recurrentinfections were similar in both groups (p > 0.05). Conclusion: Autoimmune diseases and auto antibodies were observed in IgAD patients dur-ing follow-up, reinforcing the necessity of a rigorous and continuous follow-up duringadolescence and adulthood. .

[Autoimmune diseases and autoantibodies in pediatric patients and their first-degree relatives with immunoglobulin A deficiency]. / Doenças autoimunes e autoanticorpos em pacientes pediátricos e seus parentes de primeiro grau com deficiência de imunoglobulina.

INTRODUCTION: Clinical manifestations of Immunoglobulin A Deficiency (IgAD) include recurrent infections, atopy and autoimmune diseases. However, to our knowledge, the concomitant evaluations of autoimmune diseases and autoantibodies in a cohort of IgAD patients with current age > 10 years-old and their relatives have not been assessed. OBJECTIVES: To evaluate autoimmune diseases and the presence of autoantibodies in IgAD patients and their first-degree relatives. METHODS: A cross-sectional study was performed in 34 IgAD patients (current age > 10 years-old) and their first-degree relatives. All of them were followed at a tertiary Brazilian primary immunodeficiency center: 27 children/adolescents and 7 of their first-degree relatives with a late diagnosis of IgAD. Autoimmune diseases and autoantibodies (antinuclear antibodies, rheumatoid factor, and anti-thyroglobulin, anti-thyroperoxidase and IgA class anti-endomysial antibodies) were also assessed. RESULTS: Autoimmune diseases (n=14) and/or autoantibodies (n=10, four of them with isolated autoantibodies) were observed in 18/34 (53%) of the patients and their relatives. The most common autoimmune diseases found were thyroiditis (18%), chronic arthritis (12%) and celiac disease (6%). The most frequent autoantibodies were antinuclear antibodies (2%), anti-thyroglobulin and/or anti-thyroperoxidase (24%). No significant differences were observed in the female gender, age at diagnosis and current age in IgAD patients with and without autoimmune diseases and/or presence of autoantibodies (p>0.05). The frequencies of primary immunodeficiency's in family, autoimmunity in family, atopy and recurrent infections were similar in both groups (p>0.05). CONCLUSION: Autoimmune diseases and autoantibodies were observed in IgAD patients during follow-up, reinforcing the necessity of a rigorous and continuous follow-up during adolescence and adulthood.

Serum lipids in Brazilian children and adolescents: determining their reference intervals.

BACKGROUND: Demographic, geographic, environmental and genetic factors influence lipids. In many countries, the normal lipid ranges for laboratory tests are based on references from American children and adolescents. In this work, we determined the reference intervals (RIs) for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein cholesterol (nHDL-c), low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) in Brazilian healthy children and adolescents. METHODS: A cross-sectional study was conducted of 1,866 randomly sampled healthy children and adolescents from kindergartens and schools. Blood samples were collected after a variable period of fasting based on the age of the participant. The upper cut-off points were the 75(th) and 95(th) percentiles for TC, nHDL-c, LDL-c and TG. The 10(th) percentile (low) was used as the bottom level for HDL-c. Non-parametric tests were used for statistical analyses. RESULTS: The following RI and 75(th) and 95(th) percentiles were observed for each age interval. The 95(th) percentile values obtained for TC were: 1 to 2 years, 189 mg/dL, 3 to 8 years, 199 mg/dL; 9 to 12 years, 205 mg/dL. For the nHDL c, the only age group 1 to 12 years, this percentile value was 150 mg/dL. For the LDL-cholesterol, the values corresponding to the percentiles above, aged 1 to 8 years and 9 to 12 years, were 132 mg/dL 139 mg/dL, respectively. For the triglycerides, the values corresponding to 95(th) percentile were: 1 year, 189 mg/dL; 2 to 5 years, 139 mg/dL; 6 to 12 years, 139 mg/dL . The 10(th) percentiles for HDL-c were 24 mg/dL, 28 mg/dL, 32 mg/dL and 36 mg/dL for children 1, 2, 3 and 4-12 years old, respectively. CONCLUSIONS: The lipid reference intervals defined in the studied Brazilian children and adolescents differ from those recommended by the international literature and should be used for clinical decisions contributing to improve the diagnosis in this particular group in our country.

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion / Cardiopatias Congênitas como um Sinal de Alerta para o Diagnóstico da Deleção do 22q11.2

Background: To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective: To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods: The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results: CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion: Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients. .

Fundamento: Alertar para o diagnóstico da síndrome da deleção 22q11.2 (SD 22q11.2) em pacientes com cardiopatias congênitas. Objetivo: Descrever as principais cardiopatias, alterações fenotípicas, metabólicas e imunológicas em uma série de 60 pacientes com a SD22q11.2. Métodos: Foram incluídos 60 pacientes com SD22q11.2 avaliados entre 2007 e 2013 (M:F = 1,3; idades entre 14 dias a 20 anos e 3 meses) em um centro pediátrico de referência para imunodeficiências primárias. O diagnóstico foi feito pela detecção da microdeleção 22q11.2 através de FISH (n = 18) e/ou MLPA (n = 42), associados a dados clínicos e laboratoriais. Foram analisadas as cardiopatias, aspectos fenotípicos evolutivos da fácies, a hipocalcemia e alterações imunológicas associadas. Resultados: Cardiopatias congênitas ocorreram em 77% dos casos, sendo que a tetralogia de Fallot ocorreu em 38,3%. Correção cirúrgica da cardiopatia foi realizada em 34 pacientes. Os dismorfismos craniofaciais foram detectados em 41 pacientes: face (60%) e/ou nariz alongados (53,3%), fenda palpebral estreita (50%), orelhas displásicas com hiperdobramento (48,3%), lábios finos (41,6%), dedos alongados (38,3%) e baixa estatura (36,6%). Hipocalcemia foi observada em 64,2% com redução do nível de paratormônio (PTH) em 25,9%. Observou-se número reduzido de linfócitos totais, CD4 e CD8 em 40%, 53,3%, e 33,3%, respectivamente. Detectou-se hipogamaglobulinemia em um paciente e redução das concentrações de imunoglobulina M (IgM) em outros dois pacientes. Conclusão: Deve-se suspeitar da SD22q11.2 em todos os portadores de cardiopatia congênita com hipocalcemia e/ou dismorfismos faciais, ressaltando-se que muitas dessas alterações podem ser evolutivas. ...

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion.

Background: To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective: To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods: The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results: CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion: Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.

A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome.

Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations in the AID gene (AICDA) have been found in patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- and 14-year-old Brazilian sisters, from a consanguineous family, were diagnosed with HIGM2 syndrome. Sequencing analysis of the exons from AICDA revealed that both patients are homozygous for a single C to G transversion in the third position of codon 15, which replaces a conserved Phenylalanine with a Leucine. To our knowledge, this is a new AICDA mutation found in HIGM2 patients. Functional studies confirm that the homologous murine mutation leads to a dysfunctional protein with diminished intrinsic cytidine deaminase activity and is unable to rescue CSR when introduced in Aicda(-/-)stimulated murine B cells. We briefly discuss the relevance of AICDA mutations found in patients for the biology of this molecule.

Primary immunodeficiency diseases in different age groups: a report on 1,008 cases from a single Brazilian reference center.

Primary immunodeficiencies (PIDs) represent a large group of diseases that affect all age groups. Although PIDs have been recognized as rare diseases, there is epidemiological evidence suggesting that their real prevalence has been underestimated. We performed an evaluation of a series of 1,008 infants, children, adolescents and adults with well-defined PIDs from a single Brazilian center, regarding age at diagnosis, gender and PID category according to the International Union of Immunological Societies classification. Antibody deficiencies were the most common category in the whole series (61 %) for all age groups, with the exception of <2-year-old patients (only 15 %). In the >30-year-old group, antibody deficiencies comprised 84 % of the diagnoses, mostly consisting of common variable immunodeficiency, IgA deficiency and IgM deficiency. Combined immunodeficiencies represented the most frequent category in <2-years-old patients. Most congenital defects of phagocytes were identified in patients <5 -years of age, as were the diseases of immune dysregulation, with the exception of APECED. DiGeorge syndrome and ataxia-telangiectasia were the most frequent entities in the category of well-defined syndromes, which were mostly identified in patients <10-years of age. Males represented three-quarters and two-thirds of <2 -years-old and 2-5-years -old patients, respectively, whereas females predominated among the >30-year-old patients. Our data indicated that some PIDs were only detected at early ages, likely because affected patients do not survive long. In addition, our data pointed out that different strategies should be used to search for PIDs in infants and young children as compared to older patients.

Profile of autoantibodies against phosphorylcholine and cross-reactivity to oxidation-specific neoantigens in selective IgA deficiency with or without autoimmune diseases.

Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

Presença de corantes e lactose em medicamentos: avaliação de 181 produtos / Oyes and lactose in drugs: evaluation of 181 products

Corantes e lactose são frequentemente utilizados como excipientes em medicações pediátricas e podem causar reações adversas em crianças, inclusive com manifestações clínicas graves. Objetivo: Descrever a presença de corantes e de lactose em medicamentos habitualmente utilizados em prescrições pediátricas no Brasil. Método: Para descrição dos aditivos (corante e lactose) presentes nas medicações foram utilizados para consulta bulas, bulários e registros na entidade nacional regulatória (Agência Nacional de Vigilância Sanitária). Resultados: Foram analisados 181 diferentes apresentações de 42 medicamentos sendo que para apenas quatro drogas não constavam as informações requeridas nas fontes pesquisadas. Os medicamentos foram classificados como analgésicos/antipiréticos, antiinflamatórios não esteróides, antibióticos, anti-histamínicos, antieméticos, corticóides orais, corticóides inalatórios, broilcodilatadores de ação prolongada, corticosteróides inalatórios associados a broncodilatadores, antileucotrienos e estabilizadores da membrana de mastócitos. Das 181 apresentações, 28% contêm lactose e 26% contêm algum corante. Dentre estes os mais citados foram tartrazina, amarelo crepúsculo e vermelho 40. Conclusão: A maioria dos medicamentos analisados descreve adequadamente seus excipientes em alguma das fontes pesquisadas. O conhecimento dos excipientes contidos nas formulações farmacêuticas permite a melhor adequação das prescrições pediátricas, especialmente para aqueles pacientes que já apresentaram antecedente de reação adversa medicamentosa.

Dyes and lactose are frequently used as excipients in pediatric medications and can cause adverse reactions to children, moreover severe clinicai manifestations. Objective: To describe the presence of dyes and lactose in drugs usually used in pediatric prescriptions in Brazil. Method: For description of the excipients (dyes and lactose) presented in the medications, it was performed a survey on drug labels, bulls and registrations in the National Agency of Sanitary Surveillance. Results: 181 different presentations of 42 medicines were analysed. Excipient's information was not found in the researched sources for four drugs. The medicines were c1assified as analgesic/antipyretic, non-steroidal anti-inflammatories, antibiotics, antihistamines, antiemetics, oral corticosteroids, inhaled corticosteroids, long-acting beta-agonists, inhaled corticosteroids associated with long-acting beta-agonists, antileukotrienes and mast cell stabilizers. Of the 181 presentations, 28% contain lactose and 26% contain any dye. Among these, the more frequently mentioned were tartrazine yellow, sunset yellow and red#40. Conclusion: Most of the analyzed drugs described their excipients appropriately in the researched sources. The knowledge of the excipients contained in the pharmaceutical formulations allows the best adaptation of the pediatric prescriptions, especially for those patients that have already presented any adverse drug reaction.

Neutropenia in antibody-deficient patients under IVIG replacement therapy.

Patients with antibody deficiencies are more prone to develop acute neutropenic episodes even during immunoglobulin replacement. The aims of this study were to evaluate the presence of acute neutropenia in 42 patients with primary antibody immunodeficiencies, currently receiving intravenous immunoglobulin (IVIG), and to describe the clinical and laboratory findings during neutropenic episodes. Of all patients, 10 (23.8%) presented acute neutropenia (absolute neutrophil count <1500 cells/mm3) during follow up (mean of 6.4 yr). The absolute neutrophil count ranged from 71 to 1488 cells/mm3. Neutropenia was not clearly associated with antibiotic prophylactic therapy or immunoglobulin levels, while infections were associated with neutropenia in the majority of episodes. Most acute neutropenia episodes were mild or moderate, except in CVID patients who present more severe neutropenia. Although IVIG may have contributed to reducing the severity of neutropenia, it does not prevent its occurrence in all patients. In conclusion, primary immunodeficient patients, even submitted to IVIG replacement therapy, must be regularly evaluated for neutropenia in order to minimize the risk of infections and its appropriate approach.

Prevalência de asma e fatores de risco em escolares da cidade de São Paulo / Asthma prevalence and risk factors in schoolchildren of the city of São Paulo, Brazil

OBJETIVO: Analisar a prevalência de asma e possíveis fatores de risco associados. MÉTODOS: Estudo transversal, integrante do International Study of Asthma and Allergies in Childhood. Participaram 561 escolares de seis a sete anos de idade, provenientes de 35 escolas públicas da cidade de São Paulo, escolhidas por sorteio, em 2002. A amostra incluiu 168 asmáticos e 393 não asmáticos, que responderam questionário constituído por 33 questões referentes a dados pessoais, familiares e ambientais. A associação entre asma e fatores de risco foi avaliada pela análise de regressão logística, considerando-se nível de significância estatística de 5 por cento. RESULTADOS: Entre os escolares, 31,2 por cento referiam sibilos nos 12 meses anteriores à entrevista. Os fatores de risco significativamente associados à asma foram: sexo masculino (OR=2,4;IC 95 por cento: 1,4;4,2), mãe fumante no primeiro ano de vida (OR=2,0; IC 95 por cento: 1,1;3,8), presença de eczema em locais característicos (OR=3,0; IC 95 por cento:1,2; 7,6) e rinoconjuntivite (OR=2,4;IC 95 por cento: 1,2; 4,8). CONCLUSÕES: A prevalência de asma na região estudada foi elevada e os fatores de risco relacionados foram: sexo masculino, sintomas de rinoconjuntivite no último ano, mãe fumante no primeiro ano de vida e presença de eczema em locais característicos.

[Asthma prevalence and risk factors in schoolchildren of the city of São Paulo, Brazil]. / Prevalência de asma e fatores de risco em escolares da cidade de São Paulo.

OBJECTIVE: To assess asthma prevalence and potential risk factors associated. METHODS: Cross-sectional study part of the International Study of Asthma and Allergies in Childhood. A total of 561 schoolchildren aged 6-7 years from 35 public schools in the city of São Paulo (Southeastern Brazil) were drawn to participate in the study, in 2002. The sample consisted of 168 asthmatic and 393 non-asthmatic children who answered a questionnaire comprising 33 questions on personal, family and environmental information. The association between asthma and the risk factors studied was assessed by logistic regression analysis at a 5% statistical significance. RESULTS: Among the schoolchildren studied, 31.2% reported wheezing in the 12 months preceding the interview. The following risk factors were significantly associated with asthma: male gender (OR=2.4; 95% CI: 1.4;4.2), maternal smoking in the child's first year of life (OR=2.0; 95% CI: 1.1;3.8), eczema on characteristic body areas (OR=3.0; 95% CI: 1.2;7.6) and rhinoconjunctivitis (OR=2.4; 95% CI: 1.2;4.8). CONCLUSIONS: Asthma prevalence in the study area was high and the risk factors identified were male gender, rhinoconjunctivitis in last year, maternal smoking in the child's first year of life and eczema on characteristic body areas.

Autoimmunity in IgA deficiency: revisiting the role of IgA as a silent housekeeper.

Both systemic and organ-specific autoimmune diseases are major manifestations of IgA deficiency (IgAD), the most common primary immunodeficiency. In addition, to discuss the clinical findings of IgAD patients, we proposed a hypothesis to explain the high association with autoimmune phenomena. Based on observations, interactions of monomeric IgA with FcalphaRI result in a partial phosphorylation of FcRgamma-associated FcalphaRI, notably in the immunoreceptor tyrosine-based activation motif (ITAM) inducing the recruitment of the SHP-1 tyrosine phosphatase. This leads to deactivation of several activating pathways of the immune system including immunoreceptors that bear ITAM motif and ITAM-independent receptors. Consequently, inflammatory reactions and auto-immune process would be prevented.

Guia Prático para o Manejo da Dermatite Atópica - opinião conjunta de especialistas em alergologia da Associação Brasileira de Alergia e Imunopatologia e da Sociedade Brasileira de Pediatria / Practical guide for management of atopic dermatitis - conjunct opinion of allergologists from the Associação Brasileira de Alergia e Imunopatologia and Sociedade Brasileira de Pediatria

A dermatite atópica (DA)é doença crônica e recidivante que acomete principalmente pacientes da faixa etária pediátrica. Trata-se de doença de fisiopatologia complexa que inclui o comprometimento da barreira cutânea e alterações imunológicas, desta maneira o tratamento envolve uma séria de abordagens terapêuticas ressaltando-se a orientação do paciente, restauração da barreira cutânea e controle da inflamação. Objetivo: Apresentar um guia prático para diagnóstico e tratamento dos pacientes com DA. Método: Reunião de um grupo de especialistas em alergia e imunologia, e pediatria que avaliaram publicações relacionadas ao tema incluindo os seguintes descritores: DA associada a: prevalência, fatores de risco, fatores desencadeantes, quadro clínico, diagnóstico e tratamento. Os temas foram discutidos em reuniões seriadas para elaboração deste guia que contemplou as informações da literatura adaptadas ao cotidiano do atendimento médico de DAno Brasil. Resultados: A DAapresenta no Brasil prevalência que varia entre 8,9 e 11,5 . Entre os fatores desencadeantes destacam-se os agentes infecciosos, alérgenos alimentares e aeroalérgenos. O diagnóstico é principalmente clínico e exames subsidiários podem ser auxiliares na determinação de fatores desencadeantes. O controle da doença é obtido através da adequada hidratação e do controle da inflamação através da utilização da corticoterapia tópica e dos inibidores da calcineurina. Participação em grupos de apoio e abordagem psicológica podem ser úteis e em casos graves pode ser indicada a imunosupressão sistêmica. Conclusão: A DA é doença complexa, mas a padronização de condutas terapêuticas pode ser útil no manejo destes pacientes

Assessment of muscle shortening and static posture in children with persistent asthma.

Asthmatic patients experience an increase in airway resistance that overburdens both respiratory and non-respiratory muscles. The objective of the present study was to determine whether children with persistent asthma present muscle shortening and postural changes. The 60 boys evaluated, aged 7-12 (pubertal ages up to Tanner stage G2) were divided into three age- and BMI-matched groups of equal number: CON (no history of asthma or allergy); MPA (mild persistent asthma); SPA (severe persistent asthma). Pulmonary function, muscle shortening and static posture were evaluated. The SPA group presented higher protraction of the head and shoulder compared with the CON group [9.5 (6.0-12.0) degrees vs 5.5 (0.0-12.0) degrees, P < 0.05; 0.89 (0.80-0.94) anterior/posterior ratio vs 0.94 (0.87-1.1) anterior/posterior ratio, P < 0.01)]. Severe asthmatic patients also presented shortening of arm flexor and posterior muscle of the thigh compared with the CON group [18.0 (10.0-24.0) degrees vs 12.0 (6.0-16.0) degrees, P < 0.05; and 16.5 (10.0-38.5) cm vs 8.0 (0.0-21.0) cm, respectively, P < 0.05]. Chest expansion at axillar and xiphoid levels were limited in SPA subjects compared with CON subjects [3.7 (1.5-6.5) cm vs 5.5 (2.0-8.0) cm and 4.7 (1.5-6.5) vs 6.0 (3.5-8.0) cm, respectively, P < 0.01]. SPA subjects also presented a higher incidence of lumbar spine straightening compared with CON and MPA subjects. Moderate asthmatic subjects presented intermediate values compared with severe and control subjects in five out nine evaluated outcomes. Our data suggest that severe asthmatic children present postural adaptations and muscle shortening that seem to be related to disease severity.

Risk factors for asthma in adolescents in a large urban region of Brazil.

BACKGROUND: Identify risk factors for asthma in adolescents from São Paulo, Brazil. METHODS: total of 528 adolescents (141 asthmatics, 387 control subjects) from the ISAAC study (phase III) were submitted to a complementary questionnaire to evaluate risk factors, through response to questions regarding personal history, environment, and diet and an agreement to undergo the skin prick test (SPT) for aeroallergens. RESULTS: Positive SPT to at least one allergen occurred in 49.4% adolescents. The risk factors for asthma were: prematurity (OR: 3.84, 95% CI: 1.54-9.64), rhinitis (OR: 3.18, 95% CI: 1.71-5.91), positivity in the SPT (OR: 2.81, 95% CI: 1.48-5.32), eczema in characteristic skin-folds (OR: 2.86, 95% CI: 1.13-7.26), and an allergic mother (OR: 2.01, 95% CI: 1.02-3.93). The consumption of cooked vegetables was a protective factor for asthma (OR: 0.37, 95% CI: 0.18-0.79) CONCLUSIONS: Asthma is a multifatorial disease. An allergic mother, aeroallergen sensitization, rhinitis, eczema and prematurity were considered risk factors and the consumption of cooked vegetables was considered a protective factor for asthma in this population.

Agamaglobulinemia / Agamaglobulinemia

A agamaglobulinemia é uma imunodeficiência primária decorrente de um defeito da maturação da célula B que resulta em diminuição do número de linfócitos B maduros e conseqüente produção inadequada de imunoglobulinas. A forma mais comum desta doença é a agamaglobulinemia ligada ao X causada por mutações na enzima Bruton tirosina quinase (Btk). Clinicamente os pacientes apresentam quadros infecciosos que se iniciam já no primeiro ano de vida, logo após a queda dos níveis de imunoglobulinas maternas, podendo ocorrer infecções respiratórias, cutâneas e do trato gastrointestinal, causadas principalmente por bactérias encapsuladas. Há maior susceptibilidade a infecções virais, especialmente enterovírus, que podem ocasionar quadros respiratórios graves e encefalites. Laboratorialmente, há níveis séricos bastante reduzidos de todos os anticorpos e níveis de linfócitos B circulantes inferiores a 2 por ncento. A reposição periódica de gamaglobulina por via endovenosa reduz o número de infecções e aumenta a sobrevida do pacientes. A monitorização dos níveis séricos é indicada em todos os pacientes e naqueles que apresentam complicações pulmonares, recomenda-se que seus níveis sejam mantidos superiores a 800mg/dl. A antibioticoterapia profilática é recomendada, pois os processos infecciosos podem ser insidiosos ou oligossintomáticos. As imunizações devem ser evitadas, pois são ineficientes e podem ocasionar efeitos adversos graves. Transplante de medula óssea e terapia gênica podem ser constituir alternativas futuras ao tratamento desta doença.

Anasarca e hipoalbuminemia associadas à dermatite atópica: relato de caso / Generalized edema and hypoalbuminemia associated to atopic dermatitis: case report

Objetivo: Relatar um caso de criança com Dermatite Atópica grave, que evoluiu com perda protéica e diminuição dos níveis de albumina sérica durante episódio de agudização das lesões cutâneas. Descrição do caso: Paciente de dois anos e dez meses foi encaminhado ao ambulatório de Alergia e Imunologia do Instituto da Criança - HCFMUSP com diagnóstico de Dermatite Atópica desde 18 meses de vida. Em episódio de infecção bacteriana secundária, evoluiu com edema generalizado, hipoproteinemia e hipoalbuminemia decorrente da perda cutânea de albumina sérica. Após terapêutica com antibióticos, corticoterapia tópica e sistêmica e infusão de albumina, houve melhora clínica com controle do processo inflamatório e elevação dos níveis sé ricos de albumina. comentários: Embora a hipoproteinemia secundária ao processo inflamatório da Dermatite Atópica seja uma ocorrência rara, nos casos graves deve ser realizada a avaliação dos níveis de albumina para detecção precoce e tratamento desta complicação.