Velocardiofacial syndrome in Mexican patients: Unusually high prevalence of congenital heart disease.

INTRODUCTION: Velocardiofacial syndrome (VCFS) is the most common microdeletion syndrome with an incidence of 1:4000 live births. Its phenotype is highly variable with facial, velopharyngeal, cardiac, endocrine, immunologic and psychiatric abnormalities. It is caused by a microdeletion in chromosome 22q11.2. OBJECTIVES: We present 7 years of experience evaluating patients with VCFS regarding their main clinical characteristics. MATERIAL AND METHODS: The patients included were multidisciplinary evaluated and had a positive FISH analysis for del22q11.2. RESULTS: A total of 62 patients were assessed, a 34 female/28 male ratio was observed with ages ranging from 9 days to 16 years, all but one patient had typical facial features. A diagnosis of congenital heart disease was established in 97% of the patients; other clinical characteristics were identified with different percentages such as cleft palate, and hypocalcaemia. Three cases had a familial presentation. DISCUSSION: While the clinical findings of this study were in general terms in keeping with the literature, it is interesting the unexpectedly high percentage of congenital heart disease identified in Mexican children with VCFS that also was the main cause for clinical referral.

[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.

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.

[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.

Evidence of effect of subcutaneous immunotherapy in children: complete and updated review from 2006 onward.

OBJECTIVE: To update the scientific evidence of subcutaneous immunotherapy (SCIT) in children. DATA SOURCES: PubMed, EMBASE, and known articles. STUDY SELECTION: All publications on SCIT in pediatric patients from January 2006 to April 2011. Study design was not a restriction. The articles were analyzed according to their outcomes and evaluated on their scientific quality using the Grading of Recommendations Assessment, Development, and Evaluation and Jadad tools. Clinical, safety, and immunologic data were gathered. RESULTS: The scientific evidence produced by the 31 articles analyzed showed that there is high-quality evidence that grass pollen SCIT causes a reduction in the combined symptom-medication score and increases the threshold of the conjunctival provocation test, immediately and 7 years after termination of SCIT, as well as the threshold of the specific bronchial provocation test and the skin prick test reactivity. Alternaria SCIT improves medication scores, combined symptom-medication scores, and quality of life. It augments the threshold in the nasal provocation test. High-quality evidence of house dust mite SCIT shows that asthma symptom and medication scores improve and emergency department visits and skin reactivity are reduced; moderate evidence indicates improvement in pulmonary function tests. Pollen SCIT prevents asthma (moderate evidence); evidence for long-term benefit of pollen SCIT (7-12 years after termination) is low to moderate. There is inconclusive evidence for SCIT reducing new sensitizations. CONCLUSION: There is acceptable evidence that shows that grass pollen, Alternaria, and house dust mite SCIT is beneficial in allergic children.

[Mexican clinical practice guidelines of immunotherapy 2011]. / Guía Mexicana de Práctica Clínica de Inmunoterapia 2011.

BACKGROUND: Several international guidelines on immunotherapy exist, but they only apply partially in Mexico. The Mexican guideline of immunotherapy dates from 1998. OBJECTIVES: To establish clinical recommendations and suggestions for Allergy residents and specialists for skin testing and allergen immunotherapy based on evidence and Mexican expert opinion, according to the GRADE system. METHODS: The guidelines were developed following the methodology of a guideline for clinical practice starting with the formulation of clinical questions, in the context of Mexican environmental conditions and morbidity, with the participation of allergists from all regions of the country. External validation was obtained. Its development followed three steps: 1. formulation of 24 clinical questions. 2. Search for consensus on the answers among members of the Regional chapters of both Mexican Colleges of Allergists (CMICA and COMPEDIA) during regional meetings. 3. Literature search for articles related to the questions and grading of its quality according to GRADE. RESULTS: Based on the regional consensus, 116 articles and the safety, patient acceptance/ comfort and cost clinical recommendations and suggestions were developed on basic aspects of skin testing, subcutaneous and sublingual immunotherapy (patient preparation, vial preparation and application schedules) and the treatment of eventual adverse reactions. CONCLUSIONS: A clinical guideline was developed respecting particular methodology, validated by CMICA and COMPEDIA for its implementation among Mexican allergists. Several aspects deserve further study to improve scientific evidence. KEYWORDS: Allergen immunotherapy, subcutaneous immunotherapy, sublingual immunotherapy, skin testing, allergy diagnosis, rhinitis, asthma, atopic dermatitis, house dust mite, pollens, anaphylaxis, adrenaline, Mexico.

Factors associated with allergic rhinitis in children and adolescents from northern Mexico: International Study of Asthma and Allergies in Childhood Phase IIIB.

The epidemiology of allergic diseases has not been studied extensively in Mexico. The present study, based on the International Study of Asthma and Allergies in Childhood Phase IIIB survey, reports the prevalence of allergic rhinitis and the associated risk factors in the pediatric population in four cities in northern Mexico. Children (6-7 years old) and adolescents (13-14 years old) in public elementary and secondary schools were surveyed in 2002 and 2003. The subjects were chosen randomly from Ciudad Victoria, Mexicali, Monterrey, and Tijuana. The following categories were analyzed: occurrence of rhinitis symptoms (currently or in the last 12 months), rhinoconjunctivitis symptoms, a previous diagnosis of allergic rhinitis, and relevant environmental factors. Factors associated with rhinitis that were identified previously with the chi-squared test were analyzed using logistic regression. The number of valid questionnaires was 10,892 for schoolchildren and 12,299 for adolescents. In 6- to 7-year-old children, the following frequencies were determined: rhinitis (ever), 27.9%; current rhinitis, 24.2%; rhinoconjunctivitis, 9.2%; and diagnosis of allergic rhinitis, 5.5%. The corresponding frequencies in 13- to 14-year-old children were 33.3, 34.1, 18.4, and 3.8%. In both 6- to 7-year-old and 13- to 14-year-old children, all rhinitis items were associated with asthma symptoms, dermatitis symptoms, paracetamol consumption, and maternal smoking (odds ratio, >1; p < 0.05). The main risk factors associated with allergic rhinitis symptoms in children and adolescents from cities in northern Mexico were other allergic conditions, paracetamol consumption, and passive smoking.

[Allergic bronchopulmonary aspergillosis. A report of a case and literature review]. / Aspergilosis broncopulmonar alérgica. Comunicación de un caso y revisión de la bibliografía.

Allergic bronchopulmonary aspergillosis is a world rare disease with a prevalence between 1 and 2%. It presents in moderate-severe asthma and cistic fibrosis patients. The diagnosis is made in the basis of Rossenberg and Greenberg criteria that can be essential or non essential. We present the case of a 3-year-old boy with allergic bronchopulmonary aspergillosis without bronchiectasies and with a good response to corticosteroids. His mother complained of two years of nasal obstruction, purulent rinorrea, nasal pruritus, sneezing, chronic cough and recurrent wheezing, twice to thrice a month. He also occasionally had vomits and diarrhea in relation with strawberries, banana, cow's milk and chocolate. We made the diagnosis of asthma, allergic rhinitis, sinusitis, and probably food allergy. We treated him with step approach of ICS according to GINA 2006, albuterol PRN, and elimination diet, with bad response. Laboratory exams: Blood white cells with eosinophilia (6%), total serum IgE: 1684 ng/L, aspergillus skin prick test: 4mm, serum IgG-Aspergillus fumigatus: 2.3 mcg/mL, serum IgE-Aspergillus fumigatus: negative, chest roentgenographic parahiliar and apical infiltrates, and chest computed tomography without bronchiectasies. We added prednisone to the treatment for four months, and we observed a very good response; he is now in treatment as mild persistent asthma with ICS low doses. ABPA must be suspected in patients with moderate-severe persistent asthma and a skin prick test positive to Aspergillus fumigatus regardless the age. The treatment with oral corticosteroids is the mainstream of management, and most of the patients have a good response, as we observed with this patient.

Corticosteroid therapy for refractory infections in chronic granulomatous disease: case reports and review of the literature.

BACKGROUND: Chronic granulomatous disease (CGD) is a primary phagocyte immunodeficiency. It is often accompanied by an exuberant and aberrant inflammatory response, with granulomata and obstruction of the gastrointestinal and genitourinary tracts and inflammatory bowel disease. Although corticosteroids are successful in managing the obstructive and inflammatory disorders of CGD, they are not ordinarily used for the management of infection because of the possibility of further compromising the patient's immune system. OBJECTIVES: To discuss the pros and cons of the use of corticosteroids for the treatment of infections in CGD. METHODS: We describe 2 patients with CGD and refractory infections who were successfully treated with systemic corticosteroids in addition to antimicrobial agents. We also review the medical literature in which corticosteroids have been used for CGD infection. RESULTS: Our cases add to 3 other reports in which antibiotics and corticosteroids were used successfully in patients with CGD. However, in the presence of a potential pathogen, notably, aspergilla, corticosteroids may mask or favor dissemination of the fungus, especially in adults. CONCLUSIONS: Corticosteroids may play an important adjunctive role in CGD refractory infections.