Clinical and Genotypic Spectrum of Chronic Granulomatous Disease in 71 Latin American Patients: First Report from the LASID Registry.

AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.

[Radiographic changes in children with primary immunodeficiency]. / Alteraciones radiográficas en niños con inmunodeficiencia primaria.

BACKGROUND: Although we have epidemiological information on primary immunodeficiencies (PID), the available information is meager in Mexico. OBJECTIVE: To provide epidemiological information on the delay in the diagnosis of PID and its correlation to chronic lung damage. MATERIAL AND METHOD: A retrospective, analytical study was done in patients 0-18 year old age diagnosed with PID for 11 years at the HIMFG (Hospital Infantil de Mexico Federico Gomez). The variables studied were: age at symptom onset, age at diagnosis, time from onset of symptoms to diagnosis, number of previous pneumonias and studies with radiographic chronic lung damage data. RESULTS: 48 patients were obtained after meeting inclusion criteria; 33 showed lung damage at diagnosis, antibody deficiency being the most affected group. Relating age of onset of symptoms and the time difference of the onset of symptoms to diagnosis showed a strong correlation (p < 0.001, Rho > 0.80). A moderate correlation between the observed time difference vs number of pneumonias (p=0.005, Rho=0.495) and correlation between number of pneumonia and lung damage was highly significant (p <0.001, Rho=0.704). CONCLUSION: A strong relationship between the elapsed time from onset of symptoms and the number of pneumonia with lung injury time was found. So, the recurrent pneumonia (> 2) must make suspect the diagnosis of PID, as recommended in the literature.

Antecedentes: si bien se cuenta con información epidemiológica de las inmunodeficiencias primarias, la información disponible en México es escasa. Objetivos: dar información epidemiológica del retraso del diagnóstico de las inmunodeficiencias primarias y de su correlación con daño pulmonar crónico. Material y método: estudio retrospectivo, analítico, efectuado en pacientes de 0 a 18 años de edad con diagnóstico de inmunodeficiencias primarias durante 11 años en el Hospital Infantil de México Federico Gómez; las variables estudiadas fueron: edad al inicio de los síntomas, edad al diagnóstico, tiempo desde el inicio de los síntomas al diagnóstico, número de neumonías previas y estudios radiográficos con datos de daño pulmonar crónico. Resultados: se incluyeron 48 pacientes que cumplieron los criterios de inclusión; 33 tenían daño pulmonar al diagnóstico, el déficit de anticuerpos fue el grupo con mayor afectación. Al correlacionar la edad de inicio de los síntomas y la diferencia de tiempo del inicio de los síntomas al diagnóstico se obtuvo una fuerte correlación (p <0.001, Rho > 0.80). Se observó una correlación moderada entre la diferencia en tiempo vs número de neumonías (p=0.005, Rho=0.495) y la correlación entre número de neumonías y daño pulmonar mostró significación alta (p <0.001, Rho=0.704). Conclusión: se encontró una relación estrecha entre el tiempo transcurrido desde el inicio de los síntomas y el número de neumonías con el daño pulmonar, por lo que las neumonías de repetición (más de dos) deben hacer sospechar el diagnóstico de inmunodeficiencia primaria, como se recomienda en la bibliografía mundial.

[Disseminated Tuberculosis in an Infant with IFNg-IL-12/IL 23 Axis Defect]. / Tuberculosis diseminada en un lactante con defecto innato del eje IFNg-IL 12/IL 23.

BCG vaccine contains low virulence Mycobacterium bovis bacillus. In Mexico it is given at birth with few reported adverse reactions in immunocompetent children; however, in immuno-compromised patients it can cause serious local or systemic adverse reactions. The most frequent related diseases include chronic granulomatous disease (CGD), human immunodeficiency virus infection (HIV), severe combined immunodeficiency (SCID) and mendelian susceptibility to mycobacterial disease (MSMD). At this time, the innate defect of the IFN-?/IL-12/IL-23 axis constitutes the main implied alteration in patients with MSMD. We present the case of an infant with disseminated mycobacterial infection and history of BCG given at birth and documentation of an altered functional study of the IFN-?/IL12/IL-23 axis, specifically at the IL-12 pathway, which is susceptible to improve with exogenous IFN-? administration. Treatment was started with antituberculous drugs plus subcutaneous IFN-?, with a marked clinical improvement. In children with disseminated infection by weakly virulent intracellular microorganisms, such as the species included in BCG vaccine, primary or secondary underlying immunodeficiency should be ruled out.