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ABSTRACT Objective: To report two patients with very-early-onset inflammatory bowel disease (VEOIBD) secondary to interleukin-10 receptor (IL-10R) mutations, explore immunophenotyping data and plasma cytokine profile on these cases compared to healthy controls, and describe the phenotype of IL-10/IL-10R mutations based on a literature review. Case description: We report on two female infants referred to our tertiary center at the age of ten months, with severe colonic and perianal disease, as well as significant malnutrition, who had shown limited response to usual inflammatory bowel disease (IBD) therapy agents. In the first case, whole-exome sequencing (WES) revealed a homozygous (c.537G>A/p.T179T) mutation in exon 4 of the IL-10RA gene, while in the second patient, compound heterozygosity was identified, also in the IL-10RA gene (chr11:117.859.199 variant A>G/p.Tyr57Cys and chr11: 117.860.335 variant G>T/p.Val123Leu). Both patients underwent hematopoietic cell transplantation (HCT). Immunological work-up of these patients revealed increased IL-10 plasma levels and increased IgA. Comments: Our case reports disclose novel findings on plasma cytokine profile in IL-10R deficiency, and we describe the severe phenotype of IL-10/IL-10R deficiency that should be recognized by physicians.
RESUMO Objetivo: Relatar os casos de duas pacientes com doença inflamatória intestinal de início muito precoce (em inglês VEOIBD) secundária a mutações do receptor de interleucina 10 (IL-10R), explorar dados de imunofenotipagem e perfil de citocinas plasmáticas nesses casos em comparação com indivíduos saudáveis e descrever o fenótipo de mutações IL-10/IL-10R com base em uma revisão da literatura. Descrição do caso: Duas lactentes do sexo feminino foram encaminhadas ao nosso centro terciário, ambas com dez meses no momento do encaminhamento, com doença colônica e perianal grave, bem como desnutrição significativa, tendo uma resposta limitada aos agentes de terapia usuais de doença inflamatória intestinal (DII). No primeiro caso, o sequenciamento completo do exoma revelou mutação homozigótica (c. 537G>A/p.T179T) no exon 4 do gene IL-10RA, enquanto no segundo caso heterozigosidade composta foi identificada também no gene IL-10RA [chr11: 117.859.199 - variante A>G/p.Tyr57Cys e chr11: 117.860.335 - variante G>T/ p.Val123Leu]. Ambas as pacientes foram submetidas a Transplante de Células-Tronco Hematopoiéticas. A investigação imunológica das pacientes revelou aumento dos níveis plasmáticos de IL-10 e aumento da IgA. Comentários: Nossos relatos de casos descrevem novos achados no perfil de citocinas plasmáticas na deficiência de IL-10R, e relatamos o fenótipo grave da deficiência de IL-10/IL-10R que deve ser reconhecido pelos médicos.
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INTRODUCTION: Adherence, which is crucial to the success of antiretroviral therapy (HAART), is currently a major challenge in the care of children and adolescents living with HIV/AIDS. OBJECTIVE: To evaluate the prevalence of nonadherence to HAART using complementary instruments in a cohort of children and adolescents with HIV/AIDS followed in a reference service in Campinas, Brazil. METHODS: The level of adherence of 108 patients and caregivers was evaluated by an adapted standardized questionnaire and pharmacy dispensing records (PDR). Non-adherence was defined as a drug intake lower than 95% (on 24-hour or seven-day questionnaires), or as an interval of 38 days or more for pharmacy refills. The association between adherence and clinical, immunological, virological, and psychosocial characteristics was assessed by multivariate analysis. RESULTS: Non-adherence prevalence varied from 11.1% (non-adherent in three instruments), 15.8% (24-hour self-report), 27.8% (seven-day self-report), 45.4% (PDR), and 56.3% (at least one of the outcomes). 24-hour and seven-day self-reports, when compared to PDR, showed low sensitivity (29% and 43%, respectively) but high specificity (95% and 85%, respectively). In multivariate analysis, medication intolerance, difficulty of administration by caregiver, HAART intake by the patient, lower socioeconomical class, lack of virological control, missed appointments in the past six months, and lack of religious practice by caregiver were significantly associated with non-adherence. CONCLUSION: A high prevalence of HAART non-adherence was observed in the study population, and PDR was the most sensitive of the tested instruments. The instruments employed were complementary in the identification of non-adherence.
Subject(s)
Adolescent , Child , Female , Humans , Male , Young Adult , Antiretroviral Therapy, Highly Active/statistics & numerical data , Drug Prescriptions/statistics & numerical data , HIV Infections/drug therapy , Medication Adherence/statistics & numerical data , Pharmacies/statistics & numerical data , Antiretroviral Therapy, Highly Active/psychology , Caregivers , Cross-Sectional Studies , Medication Adherence/psychology , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
OBJECTIVES: To assess sleep characteristics of adolescents infected by HIV, and to ascertain whether psychosocial aspects are associated to the quality of sleep. METHODS: A cross-sectional study assessing 102 HIV-infected adolescents of both genders, aged between 10 and 20 years-old and 120 Controls. Data collection was performed by applying the Sleep Disturbance Scale for Children, the Epworth Sleepiness Scale, and the Pediatric Quality of Life Inventory. RESULTS: A sleep disturbance prevalence of 77.4% was found in patients, and a 75% prevalence in controls, and there was correlation between quality of sleep and of life. HIV-infected adolescents scored higher for sleep breathing disorders and had higher prevalence of excessive daytime sleepiness. CONCLUSIONS: HIV-infected adolescents had similar quality of sleep compared to healthy adolescents. This may be explained by the steady improvements in daily living as a result of successful anti-retroviral therapy, and by the vulnerability that affects Brazilian adolescents living in major urban centers.
OBJETIVOS: Avaliar as características do sono de adolescentes infectados pelo HIV e estudar se os aspectos psicossociais estão associados à qualidade do sono. MÉTODOS: Estudo transversal, que avaliou 102 adolescentes, com idades entre 10 e 20 anos, infectados pelo HIV, e 120 controles, de ambos os gêneros. Para a coleta de dados, aplicaram-se: a Sleep Disturbance Scale for Children, a Epworth Sleepiness Scale, e o Pediatric Quality of Life Inventory. RESULTADOS: Verificou-se prevalência de distúrbios do sono em 77,4% dos pacientes e em 75% nos controles, e houve correlação entre qualidade do sono e de vida. Adolescentes HIV-positivos apresentaram maior pontuação nos distúrbios respiratórios do sono e maior prevalência de sonolência diurna excessiva. CONCLUSÕES: Adolescentes infectados pelo HIV apresentaram qualidade de sono semelhante à da população saudável. Isso provavelmente decorre pela melhora de suas condições de vida resultante do sucesso da terapia antirretroviral em pacientes HIV-positivos e pelas vulnerabilidades que afetam adolescentes brasileiros de grandes centros urbanos.
Subject(s)
Adolescent , Child , Female , Humans , Young Adult , Disorders of Excessive Somnolence/physiopathology , HIV Infections/physiopathology , Quality of Life , Case-Control Studies , Cross-Sectional Studies , Disorders of Excessive Somnolence/diagnosis , Socioeconomic FactorsABSTRACT
CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6 percent male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 percent (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95 percent confidence interval (CI), 1.50-8.70; aOR, 3.58; 95 percent CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95 percent CI, 1.60-53.08; aOR, 9.05; 95 percent CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.
CONTEXTO E OBJETIVO: Reações adversas a drogas são um problema significativo em pacientes sob terapia antiretroviral (TARV). Determinamos a freqüência de valores elevados de enzimas hepáticas em um grupo de crianças e adolescentes infectados pelo HIV sob TARV e os fatores de risco associados. TIPO DE ESTUDO E LOCAL: Estudo transversal, realizado na Divisão de Imunodeficiência em Pediatria, Hospital das Clínicas, Universidade Estadual de Campinas. MÉTODOS: Foram analisados prontuários médicos de 152 crianças e adolescentes (54,6 por cento masculino) infectados pelo HIV sob TARV, com dosagens de enzimas hepáticas, em média, 2,6 exames por paciente. A mediana de idade foi 7,48 anos. Clinicamente os pacientes foram classificados nas categorias N (6), A (29), B (78) e C (39). Foram avaliados os níveis séricos de aspartato aminotransferase e alanina aminotransferase. O sistema de escore da hepatotoxicidade foi: grau 1 (1,1 a 4,9 x limite superior ao normal, i.e., LSN), grau 2 (5,0 - 9,9 x LSN), grau 3 (10,0 - 15,0 x LSN) e grau 4 (>15,0 x LSN). Para determinar os fatores de risco de hepatotoxicidade, foram avaliados odds ratio (OR) e odds ratio ajustado (aOR) para idade, gênero, contagem de linfócitos TCD4+ e uso de medicações. RESULTADOS: Observamos hepatotoxicidade grau 1 em 19,7 por cento (30/152) pacientes. Não foi detectada hepatotoxicidade grau 2, 3 ou 4. Houve uma associação significativa entre a hepatotoxicidade e uso de sulfas (OR, 3,61; IC 95 por cento, 1,50 -8,70; ORajustado, 3,58; IC 95 por cento, 1,44 - 8,85) e agentes antituberculose (OR, 9,23; IC 95 por cento, 1,60 - 53,08; ORajustado, 9,05, IC 95 por cento, 1,48 - 55,25), mas não estava associada com TARV. CONCLUSÃO: Um quinto dos pacientes apresentaram hepatotoxicidade leve, atribuída ao uso de agentes antituberculose e sulfas. Nossos resultados sugerem que TARV foi bem tolerada.
Subject(s)
Adolescent , Child , Female , Humans , Male , Chemical and Drug Induced Liver Injury , Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/drug therapy , Liver/drug effects , Chemical and Drug Induced Liver Injury , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Epidemiologic Methods , Hepatitis C/chemically induced , Hepatitis C/enzymology , Liver/enzymology , Viral LoadABSTRACT
CONTEXTO E OBJETIVO: A ocorrência de desnutrição é freqüente em crianças com infecção pelo HIV. O objetivo do estudo foi estudar a ocorrência de desnutrição e sua relação com a mudança de categoria clínica em crianças infectadas pelo HIV. TIPO DE ESTUDO E LOCAL: Estudo longitudinal, no Departamento de Pediatria e Centro de Investigação em Pediatria (CIPED). Faculdade de Ciências Médicas da Universidade Estadual de Campinas (Unicamp). MÉTODOS: Revisamos os prontuários de 127 pacientes com infecção perinatal pelo HIV com o propósito de obter medidas de peso e estatura no início do acompanhamento ambulatorial, no momento da mudança de categoria clínica e cinco meses após a mudança. Estes dados foram transformados em z-escores de peso/idade, altura/idade e peso/altura. Os testes de Wilcoxon, Kruskal-Wallis e o cálculo da razão de chances foram usados. RESULTADOS: 51 (40,2%) das crianças avaliadas apresentavam desnutrição, sendo 40 (31,5%) com comprometimento de altura, e portanto com maior risco de inclusão na categoria clínica C. Encontramos associação entre condição nutricional, categoria clínica e idade no início dos sintomas. 36 (28,4%) pacientes mudaram de categoria clínica durante o acompanhamento, e a mudança ocorreu em idade mais precoce entre os desnutridos. O grupo que mudou de categoria clínica manteve as mesmas distribuições de z-escore de peso, altura e peso/altura durante o acompanhamento. CONCLUSAO: A gravidade das manifestações da aids associa-se com a condição nutricional e com a idade de início dos sintomas. A mudança de categoria clínica não se acompanhou de piora no estado nutricional.
Subject(s)
Humans , Male , Female , Child , Child Nutrition Disorders/etiology , HIV Infections/complications , Nutritional Status , Infectious Disease Transmission, Vertical , Body Height , Body Weight , Brazil , Cohort Studies , HIV Infections/transmission , Longitudinal Studies , Retrospective Studies , Severity of Illness IndexSubject(s)
Infant , Child, Preschool , Child , Adolescent , Humans , Child Health , Lung Diseases , Respiration Disorders , Respiratory Hypersensitivity , Asthma , Food HypersensitivityABSTRACT
CONTEXT: There are today only a limited number of studies defining growth parameters and nutritional status for HIV children. OBJECTIVE: To study the nutritional status of infants infected with the human immunodeficiency virus. TYPE OF STUDY: Longitudinal study. SETTING: Department of Pediatrics, Faculty of Medical Sciences, UNICAMP, Campinas, Brazil. PARTICIPANTS: One hundred and twenty-four children born to HIV infected mothers were evaluated from birth until the age of two years. They were subdivided into two groups: 71 infected children and 53 non-infected children. MAIN MEASUREMENTS: Growth was evaluated in both groups by comparing Z-scores for weight/age (w/a), length/age (H/a) and weight/length (w/H) (using the NCHS curves as reference). RESULTS: The Z-score analyses showed that there was a significant difference between the two groups for all the variables studied, except for the H/a value at 3 months of age and the W/H value at 21 months of age, which showed P > 0.05. CONCLUSIONS: The growth of infected infants was observed to be severely affected in comparison with that of seroreversed infants in the same age groups. Although clinical manifestations may take time to appear, the onset of growth changes begin soon after birth