Severe combined immunodeficiency in Brazil: management, prognosis, and BCG-associated complications.

BACKGROUND: Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency. The objectives of this study were to analyze the diagnosis, treatment, and prognosis of SCID in Brazil and to document the impact of BCG vaccine. METHODS: We actively searched for cases by contacting all Brazilian referral centers. RESULTS: We contacted 23 centers and 70 patients from 65 families. Patients were born between 1996 and 2011, and 49 (70%) were male. More than half (39) of the diagnoses were made after 2006. Mean age at diagnosis declined from 9.7 to 6.1 months (P = .058) before and after 2000, respectively, and mean delay in diagnosis decreased from 7.9 to 4.2 months (P = .009). Most patients (60/70) were vaccinated with BCG before the diagnosis, 39 of 60 (65%) had complications related to BCG vaccine, and the complication was disseminated in 29 of 39 (74.3%). Less than half of the patients (30, 42.9%) underwent hematopoietic stem cell transplantation (HSCT). Half of the patients died (35, 50%), and 23 of these patients had not undergone HSCT. Disseminated BCG was the cause of death, either alone or in association with other causes, in 9 of 31 cases (29%, no data for 4 cases). CONCLUSIONS: In Brazil, diagnosis of SCID has improved over the last decade, both in terms of the number of cases and age at diagnosis, although a much higher number of cases had been expected. Mortality is higher than in developed countries. Complications of BCG vaccine are an important warning sign for the presence of SCID and account for significant morbidity during disease progression.

Nasal provocation test (NPT) with isolated and associated dermatophagoides pteronyssinus (Dp) and endotoxin lipopolysaccharide (LPS) in children with allergic rhinitis (AR) and nonallergic controls.

BACKGROUND: Inhalation of endotoxin may enhance inflammatory airway response in sensitized asthmatics persons after allergen(s) inhalation. OBJECTIVE: To evaluate nasal response to intranasal instillation of Dermatophagoides pteronyssinus (Dp), endotoxin (LPS), and to Dp+LPS in children with perennial allergic rhinitis (PAR). METHODS: 10 PAR children (positive skin prick test to Dp) and 10 nonallergic controls (C) undergoing nasal provocation test (NPT), who were quantified by active anterior rhinomanometry and measurement of Total Nasal Resistance (TNR). The NPTs were initially performed with histamine (H; 0.03 to 16.0 mg/mL), and then, at least at weekly intervals, the NPTs were done with Dp (1/100,000 to 1/2.5), LPS (1 to 500 mg/mL) and to Dp+LPS. During NPT with Dp+LPS, Dp concentration was kept constant (1/100,000; 1/10,000; 1/1,000) and was combined with different concentrations of LPS (1, 5, 10, 20 mg/mL). The NPT was considered positive when TNR reached twice the basal TNR. RESULTS: H and Dp NPTs were positive in all AR children. In group C, H NPT was positive in 60% and Dp NPT was negative in all children. NPT with LPS was positive only in 30% of the AR children. NPT with Dp+LPS was positive in 90% of the AR patients in Dp concentration of 1/1,000 and in LPS concentrations of 5, 10, and 20 mcg/ mL. This positive association was observed with Dp concentrations lower than those obtained during NPT with Dp in 60% of AR patients. There were no changes in pulmonary function tests in all children after NPT. CONCLUSIONS: This study suggests that LPS enhances the effects of allergen challenges on nasal airflow. The daily inhalation of allergens plus endotoxin in AR patients does increase the nasal responsiveness.