Clinical manifestations and expression of CD18 to guide the diagnosis of leukocyte adhesion deficiency type 1: Mexico experience.

BACKGROUND: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking. METHODS: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed. RESULTS: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms. CONCLUSIONS: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country.

Adipokines, asymmetrical dimethylarginine, and pulmonary function in adolescents with asthma and obesity.

OBJECTIVE: This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma. METHODS: This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified. RESULTS: The obese subjects had higher levels of leptin and ADMA but lower levels of HMW adiponectin than the normal-weight subjects with or without asthma. The subjects with asthma had higher levels of RBP4 than those without asthma. The obese adolescents with asthma had lowest forced expiratory lung volume in the first second (FEV1)/forced vital capacity (FVC) ratio among the four study groups. In all the study subjects and in the subjects with asthma alone, the FEV1/FVC ratio associated negatively with leptin, however, such association was rendered non-significant when adjusted for BMI. The pulmonary function deficits associated inversely with BMI percentile in the subjects with asthma. However, the decreased FEV1/FVC ratio was not correlated with HMW adiponectin, RBP4 or ADMA. CONCLUSIONS: Our present study confirmed obstructive pattern of pulmonary function characterized by the reduced FEV1/FVC ratio in the obese adolescents with asthma. These pulmonary deficits were associated inversely with the increased BMI percentile.

Effect of six-month lifestyle intervention on adiponectin, resistin and soluble tumor necrosis factor-α receptors in obese adolescents.

The aim of this study was to evaluate the effect of a six-month lifestyle intervention on adiponectin, resistin, and two soluble forms of tumor necrosis factor-α receptor (sTNFR) in obese adolescents. A total of 54 obese adolescents aged 10 to 16 years completed the program. Twenty-four adolescents with normal weight at baseline were used as a control group. Our results demonstrated that obese adolescents had abnormal lipid profile, homeostasis model assessment (HOMA) index, adiponectin level (5.6 ± 2.7 vs. 7.6 ± 2.9 µg/mL, p = 0.005) as well as resistin level (31.0 ± 9.0 vs. 24.3 ± 8.5 ng/mL, p = 0.003), whereas levels of both sTNFRs were similar to those in normal weight subjects. After the six-month lifestyle intervention, obese adolescents had a slight but significant drop in standard deviation score-body mass index (SDS-BMI), a significant decrease in waist circumference, total cholesterol, triglycerides, HOMA index, as well as resistin, and a significant increase in adiponectin and high-density lipoprotein-cholesterol. In adolescents without decreased SDS-BMI, no change was observed in adipokines. Changes in adiponectin correlated negatively with changes in waist circumference (r = -0.275, p = 0.044). Changes in resistin correlated positively with changes in triglycerides (r = 0.302, p = 0.027). The study demonstrated the increase of resistin and the decrease of adiponectin in obese adolescents. Lifestyle intervention improved adipokine abnormalities in obese subjects.

[Absceso cerebral como manifestación inicial de Deficiencia especifica de anticuerpos].

Background: Specific antibody deficiency (SAD) is an inborn error of immunity, in patients older than 2 years, characterized by normal immunoglobulin levels and IgG subclasses, but with recurrent infections and decreased antibody responses to polysaccharide antigens. Case report: A 10-year-old female, previously healthy, with no significant family history. She is known in this institution for symptoms of headache, vomiting and paresis. A CT scan of the skull was performed, where 4 brain abscesses, edema and displacement of the midline were observed, a right frontal trephine was performed and abscess drainage, antimicrobial management for infectology, blood cultures, Gram staining and cultures of negative drainage material. Assessed for allergy and immunology, for abscesses in deep focus, an approach was performed to rule out inborn error of immunity, immunoglobulins, isohemagglutinins, flow cytometry and response to normal protein antigens. Antibodies against post-vaccination polysaccharide antigens are requested, where a response to only 2 serotypes (18.1% response) is observed, with normal IgG subclasses, a diagnosis of specific antibody deficiency is integrated and management with immuno- globulin at replacement doses is started, as well as annual vaccination with 13 valent. Conclusion: SAD has been considered a problem that can be resolved over time, especially in children, but in others it can evolve into more severe forms of humoral immunodeficiency. Decisions to treat with prophylactic antibiotics and/or gamma globulin are guided by clinical judgment, small studies, and recent consensus documents, which may evolve over time.

Antecedentes: La deficiencia especifica de anticuerpos (SAD) es un error innato de la inmunidad, en pacientes de más de 2 años, caracterizada por niveles de inmunoglobulinas y subclases de IgG normales, pero con infecciones recurrentes y respuestas de anticuerpos disminuidas a antígenos polisacáridos. Reporte de caso: Femenina de 10 años, previa sana, sin antecedentes heredofamiliares de importancia. Conocida en esta institución por cuadro de cefalea, vómi- tos y paresias. Se realiza TAC de cráneo, donde se observan 4 abscesos cerebrales, edema y desplazamiento de la línea media, se realiza trepano frontal derecha y drenaje de abscesos, manejo antimicrobiano por infectología, hemocultivos, tinción de Gram y cultivos de material de drenaje negativos. Valorado por alergia e inmunología, por abscesos en foco profundo, se realizó abordaje para descartar error innato de la inmunidad, inmunoglobulinas, isohemaglutininas, citometría de flujo y respuesta a antígenos proteicos normales. Se solicitan anticuerpos contra antígenos polisacáridos post vacunación, donde se observa respuesta a solo 2 serotipos (respuesta del 18.1%), con subclases de IgG normales, se integra diagnóstico de deficiencia especifica de anticuerpos y se inicia manejo con inmuno- globulina a dosis de reemplazo, asi como vacunación anual con 13 valente. Conclusión: El SAD se ha considerado un problema que puede resolverse con el tiempo, especialmente en niños, pero en otros puede evolucionar hacia formas más severas de inmunodeficiencia humoral. Las decisiones de tratar con antibióticos profilácticos y/o gammaglobulina están guiadas por el juicio clínico, estudios pequeños y documentos de consenso recientes, que pueden evolucionar con el tiempo.

[Food allergy, key points for clinical practice]. / Alergia alimentaria, puntos clave para la práctica clínica.

Food allergy is an immune reaction that occurs frequently at a pediatric age; its prevalence is higher in industrialized countries, affecting 8% of the population in average. The most frequently involved foods are: milk, chicken eggs, soy, peanuts, fish, wheat, seafood, and dried fruits. Food allergies can be divided into three groups: IgE-mediated, non-IgE-mediated, and mixed food allergy. The symptoms will depend on the immunological mechanisms and they can be divided into immediate or delayed symptoms; immediate symptoms appear during the first two hours after the intake, and delayed symptoms appear after the second hour and up to 72 hours. The diagnosis of food allergies requires the medical history of the patient, a physical examination, and laboratory tests; a misdiagnosis can lead to unnecessary elimination diets. The gold standard is the double-blind, placebo-controlled oral food challenge. The main treatment is food restriction, in which the entailed nutritional and psychological implications must be taken into account. Another treatment option is oral immunotherapy, which is recommended for patients who cannot carry out an elimination diet due to its significant impact on the quality of life.

La alergia alimentaria es una reacción inmunológica que se presenta de forma frecuente en la edad pediátrica; su prevalencia es mayor en los países industrializados y en promedio afecta a 8 % de la población. Los alimentos más frecuentemente involucrados son leche, huevo, soya, cacahuate, pescado, trigo, mariscos y frutos secos. La alergia alimentaria se puede dividir en tres grupos: alergia alimentaria mediada por inmunoglobulina E, no mediada por inmunoglobulina E y mixta. Los síntomas dependerán de los mecanismos inmunológicos y se pueden dividir en inmediatos o tardíos; los inmediatos se presentan en las primeras dos horas de la ingesta y los tardíos posterior a la segunda hora y hasta 72 horas. Para el diagnóstico se debe obtener la historia clínica, realizar exploración física y exámenes de laboratorio; un diagnóstico erróneo puede llevar a dietas de eliminación innecesarias. El estándar de oro es el reto oral doble ciego controlado con placebo. El tratamiento principal es la restricción del alimento, en la cual se debe tener en cuenta las implicaciones nutricionales y psicológicas que conlleva. Otro tratamiento es la inmunoterapia oral, que se recomienda en quienes no pueden llevar a cabo dieta de eliminación por la importante afectación de la calidad de vida.

Global Asthma Network Phase I study in Mexico: prevalence of asthma symptoms, risk factors and altitude associations-a cross-sectional study.

BACKGROUND: Global Asthma Network (GAN) was established in 2012 as a development to the International Study of Asthma and Allergies in Childhood to improve asthma care globally. OBJECTIVE: To survey asthma, allergic rhinitis and atopic dermatitis in primary and secondary school children and to investigate and evaluate its prevalence, severity, management and risk factors in Mexico. METHODS: GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016-2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by parents of 6-7-year-old primary school pupils (school children) and by 13-14-year-old adolescents. RESULTS: A total of 35 780 school children and 41 399 adolescents participated. Wheezing ever prevalence was 26.2% (95% CI 25.8% to 26.7%) in school children and 23.9% (95% CI 23.4% to 24.3%) in adolescents. The corresponding frequencies for current wheeze were 10.2% (95% CI 9.9% to 10.5%) and 11.6% (95% CI 11.2% to 11.9%). In school children, the risk factors for current wheeze were rhinitis (OR 4.484; 95% CI 3.915% to 5.134%) and rash symptoms (OR 1.735; 95% CI 1.461% to 2.059%). For adolescents, rhinitis symptoms (OR 3.492; 95% CI 3.188% to 3.825%) and allergic rhinitis diagnosis (OR 2.144; 95% CI 1.787% to 2.572%) were the most significant. For both groups, there was a negative relation with centres' sea level altitude higher than 1500 m above mean sea level (p<0.005). CONCLUSIONS: The most important risk factors for asthma symptoms in both age groups were the presence of rhinitis and rash symptoms or diagnosis. On the other hand, sea level altitude higher than 1500 metres was a protective factor.

[Sarcoidosis in childhood. A rare systemic disease]. / Sarcoidosis en la infancia. Una rara enfermedad sistémica.

BACKGROUND: Sarcoidosis is a systemic disease of unknown etiology that rarely occurs in children. It usually affects the lungs, however, it may involve various organs. It occasionally affects the general condition, and causes fever, hepatomegaly and splenomegaly. CASE REPORT: We report the case of a twelve-year-old adolescent with late-onset childhood sarcoidosis which diagnosis was confirmed by lymph node histopathological study. The patient presented general condition, hypercalcemia, erythema nodosum, severe lung disorders, lymphadenopathy, hepatomegaly and testicular mass. He received treatment with steroids, with excellent clinical response. CONCLUSIONS: We highlight the importance of considering the diagnosis of sarcoidosis in patients with hepatomegaly, lymphadenopathy, diffuse lung damage, erythema nodosum, testicular mass and hypercalcemia, as well as the need for a multidisciplinary approach to assess multiple organ involvement and the early beginning of steroid treatment in order to prevent the progression of the disease.

[Incontinentia pigmenti with defect in cellular immunity]. / Incontinencia pigmenti con defecto en la inmunidad celular.

BACKGROUND: Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal. CASE REPORT: We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient. CONCLUSIONS: The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications.

[Food allergy diagnosis in patients with elimination diet history. Preliminary report]. / Reporte preliminar del abordaje diagnóstico de alergia alimentaria en pacientes con antecedente de dieta de eliminación.

BACKGROUND: Food allergy diagnosis is performed by a double blind placebo controlled challenge; however, in a lot of patients, it is only based on clinical history, skin prick tests, or parents' perception. There is a high frequency of elimination diets without an adequate approach. OBJECTIVES: To analyze the results of diagnostic tests in a group of children with elimination diet-based on suspected food allergy and verify such studies with double blind placebo-controlled test challenge. MATERIAL AND METHOD: An observational, analytical and prospective study was done in a group of patients with elimination diet for suspected food allergy. We performed prick test, Prick-to-Prick test and patch test and the positive ones were verified by double-blind placebo-controlled challenge. RESULTS: Fourty-three patients were included within a total of 1,935 tests. Both approach for immediate and late sensitivity had not statistically significant relationship between a positive test and the elimination of food. Until now, we had 4 (8%) positive challenges out of 50. CONCLUSIONS: The frequency of allergy proved by double-blind placebo-controlled test in 50 challenges was of 8% (4/50), thus, in the preliminary report we found a high frequency of elimination diets without adequate support. It is very important that food allergy diagnosis is accurate and based on an appropriate approach; since the implementation of an elimination diet in pediatric population can have a negative influence on their growth and development.

Antecedentes: el diagnóstico de alergia alimentaria se realiza idealmente con reto doble ciego controlado con placebo; sin embargo, en muchas ocasiones sólo se basa en la historia clínica, en las pruebas cutáneas o, incluso, en la percepción de los padres. Con gran frecuencia se prescriben dietas de eliminación sin el abordaje adecuado. Objetivos: analizar los resultados de las pruebas diagnósticas de alergia alimentaria en un grupo de niños con dieta de eliminación y verificar esos estudios con la prueba de reto doble ciego. Material y método: estudio observacional, analítico, prospectivo, efectuado en un grupo de pacientes con dieta de eliminación por sospecha de alergia alimentaria. Se realizaron pruebas por punción, Prick-to-Prick y de parche a todos los pacientes y posteriormente se verificó la positividad de esas pruebas mediante reto doble ciego controlado con placebo. Resultados: se incluyeron 43 pacientes con un total de 1,935 pruebas. En el abordaje para sensibilidad inmediata y tardía no se encontró ninguna relación estadísticamente significativa entre la positividad de la prueba y la eliminación del alimento. Al momento se han realizado 50 retos, de los que 4 fueron positivos (8%). Conclusiones: la frecuencia de alergia comprobada por reto doble ciego controlado con placebo en 50 retos fue de 8% (4/50), por lo que en este reporte preliminar encontramos una alta frecuencia de eliminación de alimentos sin el sustento adecuado. Es muy importante que el diagnóstico de alergia alimentaria sea acertado y se base en el abordaje adecuado, porque la implementación de una dieta de eliminación en una población muy vulnerable, como los pacientes pediátricos, es de suma importancia y puede influir de manera negativa en su crecimiento y desarrollo.

Sarcoidosis en la infancia. Una rara enfermedad sistémica / Sarcoidosis in childhood. A rare systemic disease

Resumen: Introducción: La sarcoidosis es una enfermedad sistémica de etiología desconocida que raramente se presenta en la infancia. Generalmente afecta los pulmones; sin embargo, puede involucrar diversos órganos. Ocasionalmente afecta el estado general, y origina fiebre, hepatomegalia y esplenomegalia. Caso clínico: Se presenta el caso de un adolescente de doce años de edad con sarcoidosis infantil de inicio tardío, cuyo diagnóstico fue confirmado con un estudio histopatológico de ganglio linfático. El paciente cursó con afección general, hipercalcemia, eritema nodoso, alteraciones pulmonares graves, adenopatías, hepatomegalia y masa testicular. Recibió tratamiento con esteroides, con excelente respuesta clínica. Conclusiones: Se resalta la importancia de considerar el diagnóstico de sarcoidosis en los pacientes con hepatomegalia, adenopatías, daño pulmonar difuso, eritema nodoso, masa testicular e hipercalcemia, así como la necesidad del abordaje multidisciplinario para valorar el compromiso orgánico múltiple y el inicio oportuno de la terapia con esteroides, con el fin de evitar la progresión de la enfermedad.

Abstract: Background: Sarcoidosis is a systemic disease of unknown etiology that rarely occurs in children. It usually affects the lungs, however, it may involve various organs. It occasionally affects the general condition, and causes fever, hepatomegaly and splenomegaly. Case report: We report the case of a twelve-year-old adolescent with late-onset childhood sarcoidosis which diagnosis was confirmed by lymph node histopathological study. The patient presented general condition, hypercalcemia, erythema nodosum, severe lung disorders, lymphadenopathy, hepatomegaly and testicular mass. He received treatment with steroids, with excellent clinical response. Conclusions: We highlight the importance of considering the diagnosis of sarcoidosis in patients with hepatomegaly, lymphadenopathy, diffuse lung damage, erythema nodosum, testicular mass and hypercalcemia, as well as the need for a multidisciplinary approach to assess multiple organ involvement and the early beginning of steroid treatment in order to prevent the progression of the disease.

Incontinencia pigmenti con defecto en la inmunidad celular / Incontinentia pigmenti with defect in cellular immunity

ResumenIntroducción: La incontinencia pigmenti es una enfermedad genética rara ligada al cromosoma X, letal en el varón, que afecta a todos los tejidos derivados del ectodermo, como piel, faneras, ojos, dientes y sistema nervioso central, y presenta alteraciones de grado variable en la inmunidad celular. Se caracteriza por la disminución de la melanina en la epidermis y su incremento en la dermis.Caso clínico: Se presenta el caso de una lactante de dos meses de edad con incontinencia pigmenti grave, confirmada con estudio histopatológico de piel, que cursó con alteraciones neurológicas severas y crisis convulsivas. Además, presentó inmunodeficiencia celular grave que condicionó el desarrollo de infecciones que le ocasionaron la muerte.Conclusiones: Se resalta la importancia del diagnóstico clínico temprano, así como la importancia del manejo multidisciplinario de las alteraciones neurológicas y de las complicaciones infecciosas.

AbstractBackground: Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal.Case report: We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient.Conclusions: The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications.

Burkholderia cepacia y enfermedad granulomatosa crónica: Informe de un caso / Burkholderia cepacia and chronic granulomatous disease: a case report

Introducción. La enfermedad granulomatosa crónica (EGC) es una inmunodeficiencia que se caracteriza por un defecto en la fagocitosis, por lo que generalmente sus manifestaciones iniciales son las de las infecciones con las que cursa. Se trata de una enfermedad poco frecuente cuyo diagnóstico siempre es un reto. Caso clínico. Se presenta el caso de un escolar previamente sano, quien acudió por presentar fiebre de origen oscuro. Se estableció el diagnóstico de neumonía persistente que requirió decorticación. En el cultivo de la biopsia pulmonar creció Burkholderia cepacia. Debido a que esta bacteria se ha relacionado con pacientes inmunodeficientes, se realizaron pruebas para descartar inmunodeficiencia, con lo que se estableció el diagnóstico de EGC. Conclusión. Se propone que el aislamiento de B. cepacia debe obligar al clínico a descartar inmunodeficiencia.

Introduction. Chronic granulomatous disease (CGD) is an immunodeficiency characterized by a defect of phagocitosis, so initial manifestations are those from the secondary infection. It is an uncommon disease, whose diagnosis is always a challenge. Case report. The case of a previously healthy boy who came to the hospital with fever of unknowns origin is presented. He was diagnosed with persistent pneumonia that required decortication. Burkholderia cepacia grew from the lung biopsy culture. Because this bacteria has been related to immunodeficient patients, screening for immunodeficiency were performed and the diagnosis of CGD was established. Conclusion. Immunodeficiency should be ruled out in patients with infections due to B. cepacia.