Chronic granulomatous disease in pediatric patients: 25 years of experience / Enfermedad granulomatosa crónica en pediatría: 25 años de experiencia

ABSTRACT

Introduction: Chronic granulomatous disease (CGD) is an uncommon primary immune deficiency (affecting 1/200,000 newborn infants) caused by a defect in phagocyte production of oxygen metabolites, and resulting in bacterial infections produced by catalase-positive microorganisms and fungal diseases that occasionally may prove fatal. Methods: A review is made of the clinical records of 13 pediatric patients diagnosed with CGD between 1980 and 2005. Results: All patients were males. The mean age at diagnosis was 36 months. The clinical manifestations at the time of diagnosis comprised the following Abscesses or abscessified adenopathies 4/13 (Staphylococcus aureus (2), Serratia liquefaciens, S. marcescens and Klebsiella sp.), pneumonia 3/13 (Rhodococcus equi, Salmonella typhimurium plus Pneumocystis jiroveci), osteomyelitis 1/13 (Aspergillus sp.), sepsis 1/13 (S. aureus), urinary infection 1/13 (Klebsiella sp.), severe gastroenteritis 1/13, oral aphthae 1/13 and Crohn-like inflammatory bowel disease 1/13. The diagnosis was initially established by the nitroblue tetrazolium test, and confirmed by flow cytometry 10/13 and genetic techniques (gp91) 9/13. In the course of these disease processes there were 88 infections abscesses (n = 26), lymphadenitis (n = 12), pneumoniae (n = 10), gastroenteritis (n = 7), sepsis (n = 6), osteomyelitis (n = 3) and others (n = 24). As to the germs isolated, the frequency distribution was as follows (n = 49) Aspergillus sp. (n = 10), Staphylococcus sp. (n = 7), Salmonella sp. (n = 6), Serratia sp. (n = 5), Pseudomonas aeruginosa (n = 4), Klebsiella sp. (n = 4), Proteus sp. (n = 3), Leishmania sp. (n = 2) and others (n = 8). IFN-ã was administered in 7/13 cases, and itraconazole in 9/13; all received cotrimoxazole. There were four deaths, with one case each of sepsis due to gramnegative bacterial infection; disseminated aspergillosis; visceral leishmaniasis and hemophagocytosis; and post-kidney transplant complications. Conclusions: Clinical suspicion and flow cytometry are the keys for diagnosis of CGD and detection of carrier relatives. Specific prophylactic measures and medical controls are required to prevent serious infections. IFN-gamma has been used intermittently, though its effectiveness is controversial

RESUMEN

Introducción: La enfermedad granulomatosa crónica (EGC) es una inmunodeficiencia primaria infrecuente (1/200.000 recién nacidos vivos) por defecto de la producción de metabolitos del oxígeno por los fagocitos, causando infecciones bacterianas por microorganismos catalasa positivos y fúngicas, en ocasiones letales. Métodos: Revisión de historias clínicas de 13 pacientes diagnosticados de EGC en edad pediátrica de 1980 a 2005. Resultados: 100% varones. Edad mediana al diagnóstico 36 meses. Clínica al diagnóstico abscesos o adenopatías abscesificadas 4/13 (Staphylococcus aureus (2), Serratia liquefaciens, S. marcescens y Klebsiella sp.), neumonía 3/13 (Rhodococcus equi, Salmonella typhimurium más Pneumocystis jiroveci), osteomielitis 1/13 (Aspergillus sp.), sepsis 1/13 (S. aureus), infección urinaria 1/13 (Klebsiella sp.), gastroenteritis grave 1/13, aftas orales 1/13 y enfermedad inflamatoria intestinal Crohn-like 1/13. Diagnosticados inicialmente por Nitroblue Tetrazolium Test, confirmados por citometría de flujo 10/13 y genéticamente (gp91) 9/13. En su evolución presentaron 88 infecciones abscesos (26), adenopatías (12), neumonías (10), gastroenteritis (7), sepsis (6), osteomielitis (3) y otras (24). Gérmenes aislados (49) Aspergillus sp. (10), Staphylococcus sp. (7), Salmonella sp. (6), Serratia sp. (5), Pseudomonas aeruginosa (4), Klebsiella sp. (4), Proteus sp. (3), Leishmania sp. (2) y otros (8). Han recibido Interferón Gamma 7/13; itraconazol 9/13 y todos cotrimoxazol. Cuatro fallecidos (1 sepsis por un bacilo gram negativo, 1 aspergilosis diseminada, 1 leishmaniasis visceral y hemofagocitosis, 1 complicaciones post-trasplante renal). Conclusiones: La sospecha clínica y la citometría de flujo son los pilares del diagnóstico en la EGC para el paciente y para la detección de familiares portadores. Debemos establecer una profilaxis específica y controles médicos para prevenir infecciones graves. Se ha usado intermitentemente IFN-gamma, aunque su efectividad es discutida