RESUMO
We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígenos CD40/imunologia , Infecções por Enterovirus/etiologia , Hipergamaglobulinemia/complicações , Hipergamaglobulinemia/genética , Imunoglobulina M/sangue , Glicoproteínas de Membrana/genética , Meningoencefalite/etiologia , Mutação , Ligante de CD40 , Análise Mutacional de DNA , Citometria de Fluxo , Ligação Genética , Humanos , Hipergamaglobulinemia/terapia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Ligantes , Ativação Linfocitária , Masculino , Linhagem , Pneumonia por Pneumocystis/complicações , Reação em Cadeia da Polimerase , Síndrome , Cromossomo XRESUMO
OBJECTIVE: To compare the efficacy, safety, and tolerance of fluconazole suspension versus nystatin in the treatment of oropharyngeal thrush in immunocompromised children. DESIGN: Multicenter, randomized, observer-masked trial. SETTING: Thirty-two centers participated, including hospitals and ambulatory care clinics. PATIENTS: We enrolled 182 immunocompromised infants and children, ages 5 months to 14 years, with signs of oral thrush and presence of yeasts on potassium hydroxide- or gram-stained preparations. Subjects were randomly assigned to receive a single daily dose of fluconazole suspension, 2 to 3 mg/kg per day, or nystatin, 400,000 units four times daily for 14 days; 159 patients, who had culture confirmation of thrush and received at least 7 days of study drug, were evaluated for efficacy; all patients were evaluated for safety. RESULTS: Clinical cure was demonstrated in 91% of the subjects in the fluconazole group and 51% of the subjects in the nystatin group (p < 0.001), and eradication of the organism cultured at entry occurred in 76% and 11% (p < 0.001), respectively. Gastrointestinal conditions developed in six patients who received fluconazole and in three who received nystatin; two fluconazole recipients were subsequently withdrawn from the study. Laboratory abnormalities occurred with equal frequency in both groups. Clinical relapse rates were similar in both groups at 2 weeks (18% and 24% for fluconazole and nystatin, respectively) and 1 month (28% and 27%, respectively) after the completion of study drug. CONCLUSIONS: Fluconazole suspension is more effective than nystatin in the treatment of thrush in immunocompromised children. Both regimens were well tolerated.