Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Immediate infusion-related adverse reactions to intravenous immunoglobulin in a prospective cohort of 1765 infusions.

Intravenous immunoglobulin (IVIG) is increasingly recommended for many diseases apart from primary immunodeficiency diseases (PID). Although effective and safe, adverse reactions may occur. We conducted a 2-year prospective observational study in 117 patients with PID who received regular IVIG replacement therapy at a median dose of 600 mg/kg every 3 to 4 weeks to examine IVIG's adverse effects; 1765 infusions were performed (mean=15/patient) in 75 males and 42 females (aged 3 months to 77 years) in 3 groups: ≤ 9 years (34.2%), 10-19 years (26.5%), and ≥ 20 years (39.3%). Fifty patients had common variable immunodeficiency (CVID), 11 had X-linked agammaglobulinemia (XLA), and 55 had other immune system disorders. The drugs administered were Octagam® (49.1%), Tegeline® (17.3%), Imunoglobulin® (18.6%), Flebogama® (12.9%), Vigam® (1.2%), and Kiovig® (0.4%). Immediate infusion-related adverse reactions occurred in the cases of 38 out 1765 infusions (2.15%, IC95% 1.53%-2.94%), which were classified as mild (81.6%), moderate (10.5%), or severe (7.9%). Time until reaction ranged from 10 to 240 min (mean = 85.7, median = 60). Reaction rates were similar across age groups. The most common reactions were malaise, headache, and abdominal pain. Reported severe events were tightness of the throat and seizure. All symptoms improved with temporary or complete IVIG interruption and symptomatic medications. Sixteen of 38 reactions to infusions occurred in the presence of an acute infection (p=0.09). Tegeline® represented a greater reaction risk factor than Octagam® (p < 0.001). These results indicate that IVIG infusion can be considered a safe procedure. Low reaction incidence and few severe immediate infusion-related adverse reactions were observed.

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/µL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/µL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.