RESUMO
BACKGROUND: SCID are characterized by an imbalance in cellular and humoral immunity. Enzyme ADA deficiency represents from 10% to 15% of the SCID. This generates diminished maturation of the cell precursors. Treatments include enzyme replacement therapy, allogenic, or autologous HSCT with gene therapy, with HSCT being of choice when an identical HLA donor exists. CASE REPORT: Male patient, without relevant family antecedents or consanguinity. The patient had multiple infections during the first months of life, evidencing low immunoglobulin levels, with absence of T and B lymphocytes, and natural killer cells. Severe combined immunodeficiencies are considered due to ADA deficiency; management was begun and is derived to our hospital. Admission at 8 months of life, with chronic malnutrition and psychomotor retardation. The HLA studies were conducted without finding an identical donor, taken to HSCT with haploidentical donor. Conditioning regimen with cyclophosphamide, fludarabine, melphalan, and thymoglobulin. This patient received prophylaxis for graft-versus-host disease with cyclophosphamide, cyclosporine, and methotrexate. A 22 months post-transplant, the patient was without immunosuppressants or immunoglobulin, without evidence of graft-versus-host disease or new infections. CONCLUSIONS: The ADA deficiency is an infrequent pathology that can be potentially fatal if adequate treatment is not started. Haploidentical HSCT, using post-transplantation cyclophosphamide, emerges as a viable option with which good results can be achieved and improve the quality of life in patients with no other therapeutic alternatives.
Assuntos
Agamaglobulinemia/terapia , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Imunodeficiência Combinada Severa/terapia , Humanos , Lactente , Masculino , Condicionamento Pré-TransplanteRESUMO
BACKGROUND: Primary immunodeficiencies are diseases that are caused by one or more defects in the immune system. OBJECTIVE: The purpose of the article is to describe the characteristics of the immunodeficiencies that were diagnosed in a pediatric hospital, which forms a reference center in the West of Mexico. METHODS: A cross-sectional study of pediatric patients with primary immunodeficiency in a pediatric hospital in Guadalajara, Jalisco. RESULTS: 60 patients were registered, of which 21% were female, and 78% were male. Predominant immunodeficiencies of antibodies formed the largest group (46% of patients). X-linked agammaglobulinemia was the most frequent immunodeficiency (21%); other frequent diagnoses were common variable immunodeficiency, and IgG subclass deficiency. The average age of the patients that were diagnosed was of 6.3 years. The most common initial manifestations were infectious processes (46%), and pneumonia was the frequent diagnosis (30%). Autoimmune manifestations were observed in 13% of patients; 67% of the patients were found with immunoglobulin replacement therapy, with which a decrease in hospitalizations from 3.2 times to 0.13 times was observed. There were two deceased patients due to surgical complications of cardiac correction and intestinal reconnection. CONCLUSION: Knowing the behavior of primary immune deficiencies in our environment allows the opening of areas of opportunity in order to improve the survival and quality of life of our patients.
Antecedentes: Las inmunodeficiencias primarias son un grupo de enfermedades causadas por uno más defectos del sistema inmunitario. Objetivo: Describir las características de las inmunodeficiencias diagnosticadas en un hospital pediátrico de tercer nivel, que constituye un centro de referencia en el Occidente de México. Métodos: Estudio transversal de pacientes pediátricos con inmunodeficiencias primarias atendidos en un hospital pediátrico en Guadalajara, Jalisco. Resultados: Se registraron 60 pacientes, 21 % mujeres y 78 % hombres. Las inmunodeficiencias predominantes de anticuerpos constituyeron el grupo más numeroso (46 %). La agammaglobulinemia ligada al cromosoma X fue la inmunodeficiencia más frecuente, con 21 % del registro. Otros diagnósticos frecuentes fueron inmunodeficiencia común variable y deficiencia de subclases de IgG. El promedio de edad al diagnóstico fue de 6.3 años. Las manifestación inicial más común fueron los procesos infecciosos (46 %) y la neumonía fue el diagnóstico más frecuente (30 %). Las manifestaciones autoinmunes se observaron en 13 % de los pacientes; 67 % de los pacientes se encontró con sustitución de inmunoglobulina, con la cual se observó disminución en las hospitalizaciones: de 3.2 a 0.13 veces. Fallecieron dos pacientes por complicaciones quirúrgicas de corrección cardiaca y reconexión intestinal. Conclusión: El conocimiento del comportamiento de las inmunodeficiencias primarias en nuestro medio permite apertura de áreas de oportunidad a fin de mejorar la supervivencia y calidad de vida de los pacientes.
Assuntos
Agamaglobulinemia , Síndromes de Imunodeficiência , Doenças da Imunodeficiência Primária , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/terapia , Criança , Estudos Transversais , Feminino , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/terapia , Masculino , Qualidade de Vida , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Good's syndrome is an association of thymoma and immunodeficiency. The symptoms are recurrent sinopulmonary infections in addition to the compressive side of thymoma. A laboratory finding is notable for the absence or decrease of B lymphocytes, hypogammaglobulinemia, inversion ratio CD4/CD8 and abnormal proliferative response to mitogens. CASE REPORT: Female, 49-year-old started five months earlier with lower limb edema, postprandial vomiting, dysphagia, chronic diarrhea and weight loss. A second endoscopy ruled gastric neoplasia. Chest radiography with mediastinal widening, Thoraco-abdominal CT with bilateral pleural effusion and a mass in the anterior mediastinum, histopathological report of the tumor: B1 thymoma. Laboratory findings: IgG 349 mg/dL, IgA 70.3 mg/dL, 37.1 IgM mg/dL, Ca125 631 UI/mL, leukocytes 7890 mm3, hemoglobin 13.2 g/dL, lymphocytes 2060 mm3, CD16+CD56+ 122 cells/µL, CD19 77 cells/µL, CD3 2052 cells/µL, CD4 977 cells/µL, CD8 998 cells/µL; ratio CD4/CD8 0.98, hepatitis C, B and HIV negative. They requested valuation to Clinical Immunology and Allergy due to hypogammaglobulinemia, the diagnosis of Good's syndrome was confirmed and initiated with intravenous gamma globulin replacement to immunomodulatory dose of 1 g/kg, she reached replacement goal in the third dose of immunoglobulin intravenous, with clinical improvement. She died four months later from cardiac complications. CONCLUSIONS: Despite the variability of presentation, Good's syndrome should be suspected as part of the paraneoplastic manifestations of thymoma.
Introducción: El síndrome de Good es una asociación de timoma e inmunodeficiencia. Los síntomas son infecciones sinopulmonares recurrentes, además de los provocados por la compresión del timoma. Los exámenes paraclínicos se caracterizan por ausencia o disminución de linfocitos B, hipogammaglobulinemia, inversión de la relación CD4/CD8 y respuesta proliferativa anormal a mitógenos. Caso clínico: Mujer de 49 años de edad con edema de miembros inferiores, vómito posprandial, disfagia, diarrea crónica y pérdida ponderal. Con una segunda endoscopia se descartó cáncer gástrico. En la placa de tórax se observó ensanchamiento de mediastino y en la tomografía toracoabdominal, derrame pleural bilateral y tumor en mediastino anterior. El reporte histopatológico fue timoma B1. Exámenes paraclínicos: IgG, IgA e IgM de 349, 70.3 y 37.1 mg/dL, respectivamente; Ca125 631 UI/mL, leucocitos 7890 mm3, hemoglobina 13.2 g/dL, linfocitos 2060 mm3; CD16+CD56+, CD19, CD3, CD4 y CD8 de 122, 77, 2052, 977 y 998 cel/µL, respectivamente; relación CD4/CD8 0.98; panel viral para hepatitis C, B y VIH negativo. La hipogammaglobulinemia confirmó síndrome de Good; se inició con 1 g/kg de gammaglobulina intravenosa, alcanzando meta de reemplazo a la tercera dosis, con mejoría clínica. La paciente falleció a los 4 meses por complicaciones cardiacas. Conclusiones: A pesar de la variabilidad de la presentación del síndrome de Good, debe sospecharse como parte de las manifestaciones paraneoplásicas del timoma.
Assuntos
Síndromes de Imunodeficiência/etiologia , Síndromes Paraneoplásicas/etiologia , Timoma/complicações , Neoplasias do Timo/complicações , Agamaglobulinemia/etiologia , Agamaglobulinemia/terapia , Doenças Cardiovasculares/etiologia , Diagnóstico Diferencial , Edema/etiologia , Evolução Fatal , Feminino , Gastroenteropatias/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/terapia , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico , Síndrome , Timoma/diagnóstico , Neoplasias do Timo/diagnósticoAssuntos
Agamaglobulinemia/diagnóstico , Transplante de Medula Óssea , Reação Enxerto-Hospedeiro , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Transplante de Células-Tronco , Agamaglobulinemia/terapia , Diagnóstico Diferencial , Humanos , Lactente , Recém-Nascido , Triagem NeonatalRESUMO
INTRODUCTION: Argentina has a large number of patients with definite diagnosis of X-linked agammaglobulinemia reported in the Latin-American registry. Forty-nine of them were seen in our referral pediatric hospital, between 1987 and 2005. RESULTS AND DISCUSSION: A retrospective study of clinical, laboratory, and molecular data showed that respiratory tract infections were the most frequent initial clinical presentation and the most common among all manifestations prior to diagnosis (69%). Up to diagnosis, we found a high frequency of severe infections (sepsis, 14% and meningitis, 16%) and a high proportion of patients with chronic lung disease. During follow-up, the development of chronic lung disease was significantly related with age at diagnosis and inappropriate treatment. CONCLUSION: Although molecular diagnosis has been available in our center for the past 10 years, there is no doubt that awareness for early recognition of immunodeficiency should be improved through broader and more comprehensive education programs emphasizing characteristics of patients with immunodeficiencies.
Assuntos
Agamaglobulinemia/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Adolescente , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/complicações , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/genética , Agamaglobulinemia/terapia , Argentina , Criança , Pré-Escolar , Doença Crônica , Diagnóstico Precoce , Feminino , Seguimentos , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Imunoglobulinas/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Pneumopatias/diagnóstico , Pneumopatias/etiologia , Pneumopatias/imunologia , Masculino , Mutação/genética , Proteínas Tirosina Quinases/genética , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Infecções Respiratórias/imunologia , Estudos RetrospectivosRESUMO
BACKGROUND: The primary immunodeficiency diseases cause a deficit in the production of antibodies. The chronic sinopulmonary disease is common and their clinic symptoms are diverse (pneumonia, bronchiectasis). OBJECTIVE: To know the frequency and type of pulmonary abnormalities in patients with primary immunodeficiency in treatment with intravenous immunoglobulin. MATERIAL AND METHODS: 24 files of patients with primary immunodeficiency were selected. Age, sex, primary immunodeficiency type, time of immunoglobulin treatment, chest X-ray finding, pulmonary computed tomography of high resolution (HRCT) and pulmonary function tests were registered. Measures of central tendency were calculated. RESULTS: There was no predominance of gender; the average age was 14 years old. The common variable immunodeficiency and the Bruton's hypogammaglobulinemia represented 91% of the patients. The X-ray of thorax was abnormal in 33%, although there were not bronchiectasis. The high-resolution computed tomography scan (HRCT) was abnormal in 67%, and 75% had bronchiectasis. CONCLUSIONS: The pulmonary complications are common despite therapy with intravenous immunoglobulin. The HRCT is better than X-ray in these patients.
Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/complicações , Pneumopatias/epidemiologia , Adolescente , Adulto , Agamaglobulinemia/complicações , Agamaglobulinemia/terapia , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/epidemiologia , Bronquiectasia/imunologia , Bronquiectasia/fisiopatologia , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/terapia , Suscetibilidade a Doenças , Feminino , Humanos , Síndromes de Imunodeficiência/terapia , Pneumopatias/diagnóstico por imagem , Pneumopatias/imunologia , Pneumopatias/fisiopatologia , Pneumopatias/prevenção & controle , Masculino , Prevalência , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/complicações , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/terapiaRESUMO
To evaluate the effect of bacterial antigen lysate on serum immunoglobulin (Ig) levels, we studied 14 children with recurrent infections and hypogammaglobulinemia (IgG and IgA levels below 2 standard deviations for age). Patients were treated for a 60-90 day period with OM-85 BV and reevaluated both clinically and by measuring serum Ig levels at the end of follow-up. The control group consisted of 10 children with recurrent infections who received a placebo. Serum Ig levels were also compared with the reference values for age. The Wilcoxon and Mann-Whitney tests were used for statistical analysis. In the study group, IgG (pretreatment: 707 mg/dl; post-treatment: 1,022 mg/dl; p < 0.004) and IgA levels (pretreatment: 41 mg/dl; post-treatment: 83 mg/dl; p < 0.018) increased significantly. Furthermore, 13/14 children reached normal IgG levels, and 12/14 children reached normal age levels for serum IgA. Similarly, when comparing the pre- and post-treatment levels in the study group with the levels in the control group, they were significant for IgG (p < 0.002) as well as IgA levels (p < 0.04). The overall clinical response was favorable in all patients in the treated group. These results suggest an immunostimulant effect of OM-85 BV, both improving Ig levels and reducing recurrent infections.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Agamaglobulinemia/terapia , Antígenos de Bactérias/farmacologia , Bactérias , Extratos Celulares , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Indutores de Interferon/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Infecções Respiratórias/sangueRESUMO
OBJECTIVE: To evaluate the outcome of children who received prolonged intravenous immunoglobulin (IVIg) replacement therapy early in life for X-linked agammaglobulinemia (XLA). STUDY DESIGN: We performed a retrospective study of the clinical features and outcome of patients with genetic and/or immunologic results consistent with XLA. Patients receiving IVIg replacement therapy within 3 months of the diagnosis and for at least 4 years between 1982 and 1997 were included. RESULTS: Thirty-one patients began receiving IVIg replacement therapy at a median age of 24 months and were followed up for a median time of 123 months. IVIg was given at doses >0.25 g/kg every 3 weeks, and mean individual residual IgG levels ranged from 500 to 1140 mg/dL (median, 700 mg/dL). During IVIg replacement, the incidence of bacterial infections requiring hospitalization fell from 0.40 to 0.06 per patient per year (P <. 001). However, viral or unidentified infections still developed, including enteroviral meningoencephalitis (n = 3) causing death in one patient, exudative enteropathy (n = 3), and aseptic arthritis (n = 1). At last follow-up, 30 patients were alive at a median age of 144 months (range, 58 to 253 months). Among 23 patients who were evaluated by respiratory function tests and computed tomography, 3 had an obstructive syndrome, 6 had bronchiectasis, and 20 had chronic sinusitis. CONCLUSION: Early IVIg replacement therapy achieving residual IgG levels >500 mg/dL is effective in preventing severe acute bacterial infections and pulmonary insufficiency. More intensive therapy may be required to fully prevent the onset of bronchiectasis, chronic sinusitis, and nonbacterial infections, particularly enteroviral infections, in all cases.