Severe adenovirus infection outbreak in Colombia: Experience from a tertiary pediatric hospital in 2022. / Brote de adenovirus grave en Colombia: experiencia de un hospital pediátrico de tercer nivel en 2022

Introduction. During the SARS-CoV-2 pandemic, many countries experienced decreased respiratory virus circulation, followed by an out-of-season outbreak. In a pediatric hospital in Colombia, we observed a surge in severe adenovirus infections, leading to concerns about the impact of eased public health restrictions and immune debt in children under five years old. Objective. To describe the clinical characteristics of patients with severe adenovirus infection in a pediatric hospital in Colombia. Materials and methods. We reviewed the data of 227 patients with severe adenovirus infection at the Fundación Hospital Pediátrico La Misericordia. Results. A total of 196 patients were included in this study. The median age was two years, and 62% were male. Adenoviruses were isolated from all patients' samples. Ninetyseven percent were admitted to the pediatric intensive care unit, 94% required respiratory support, and the in-hospital lethality rate was 11%. Conclusion. In 2022, there was an outbreak of severe adenovirus infections, affecting mainly children under five years of age, with higher-than-usual mortality.

Introducción. Durante la pandemia por SARS-CoV-2, muchos países evidenciaron una disminución en la circulación de virus respiratorios, seguida por un brote fuera de la temporada esperada. En un hospital de Colombia, se observó un aumento en los casos de infección grave por adenovirus, lo cual generó preocupación sobre el impacto que tuvo la disminución de los cuidados establecidos durante pandemia y la posible deuda inmunológica en niños menores de cinco años. Objetivo. Describir las características clínicas de los pacientes con infección grave por adenovirus en un hospital pediátrico de Colombia. Materiales y métodos. Se revisaron 227 pacientes con infección grave por adenovirus en la Fundación Hospital Pediátrico La Misericordia, desde el 1° de enero hasta el 31 de diciembre de 2022. Resultados. El estudio incluyó 196 casos. La edad media de los pacientes fue de dos años y el 62 % eran de sexo masculino. Los adenovirus se aislaron a partir de las muestras de todos los pacientes. El 97 % de los pacientes ingresó a la unidad de cuidados intensivos, el 94 % requirió soporte ventilatorio y la tasa de mortalidad fue del 11 %. Conclusiones. En el 2022 hubo un brote de adenovirus que afectó principalmente a los niños menores de cinco años, con una mortalidad mayor a lo reportado con anterioridad en Colombia.

STK4 deficiency and epidermodysplasia verruciformis-like lesions: A case report.

Serine/threonine kinase 4 deficiency (STK4 or MST1, OMIM:614868) is an autosomal recessive (AR) combined immunodeficiency that can present with skin lesions such as epidermodysplasia verruciformis-like lesions (EVLL). Herein, we describe a 17-year-old male patient born from consanguineous parents presenting with recurrent respiratory infections, verruciform plaques, poikiloderma, chronic benign lymphoproliferation, and Sjögren syndrome with suspected interstitial lymphocytic pneumonia.

Why are you hitting yourself? Whole-exome sequencing diagnosis of monogenic autoimmunity.

Inborn errors of immunity may present with autoimmunity and autoinflammation as hallmark clinical manifestations. We aimed to identify the potential monogenic causes of autoimmune disorders in 26 patients from a pediatric reference hospital in Mexico through whole-exome sequencing. We specifically selected patients with a family history of autoimmune diseases, early-onset symptoms, and difficult-to-control autoimmune disorders or autoimmunity associated with infection predisposition. We identified the genetic variants that were compatible with the patients' phenotype in 54% of the patients. Autoimmune diseases are often caused by a combination of genetic factors, but cases that appear at a young age are resistant to treatment or occur in clusters, as well as the presence of autoimmune symptoms alongside infectious diseases should raise suspicion for an underlying inborn error of immunity.

Clinical characterization and outcomes of a cohort of colombian patients with AL Amyloidosis.

Background: Amyloid light chain (AL) amyloidosis is characterized by amyloid fibril deposition derived from monoclonal immunoglobulin light chains, resulting in multiorgan dysfunction. Limited data exist on the clinical features of AL amyloidosis. Objective: This study aims to describe the clinical characteristics, treatments, and outcomes in Colombian patients with AL amyloidosis. Methods: A retrospective descriptive study was conducted at three high-complexity centers in Medellín, Colombia. Adults with AL amyloidosis diagnosed between 2012 and 2022 were included. Clinical, laboratory, histological, treatment, and survival data were analyzed. Results: The study included 63 patients. Renal involvement was most prevalent (66%), followed by cardiac involvement (61%). Multiorgan involvement occurred in 61% of patients. Amyloid deposition was most commonly detected in renal biopsy (40%). Bortezomib-based therapy was used in 68%, and 23.8% received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). Hematological response was observed in 95% of patients with available data. Cardiac and renal organ responses were 15% and 14%, respectively. Median overall survival was 45.1 months (95% CI: 22.2-63.8). In multivariate analysis, cardiac involvement was significantly associated with inferior overall survival (HR 3.27; 95% CI: 1.23-8.73; p=0.018), HDCT-ASCT had a non-significant trend towards improved overall survival (HR 0.25; 95% CI: 0.06-1.09; p=0.065). Conclusions: In this study of Colombian patients with AL amyloidosis, renal involvement was more frequent than cardiac involvement. Overall survival and multiorgan involvement were consistent with data from other regions of the world. Multivariate analysis identified cardiac involvement and HDCT-AHCT as possible prognostic factors.

Antecedentes: La amiloidosis por amiloide de cadenas ligeras (AL) se caracteriza por el depósito de fibrillas amiloides derivadas de cadenas ligeras de inmunoglobulinas monoclonales, lo que resulta en disfunción multiorgánica. Existen datos limitados sobre las características clínicas de la amiloidosis AL. Objetivo: Este estudio tiene como objetivo describir las características clínicas, tratamientos y desenlaces en pacientes colombianos con amiloidosis AL. Métodos: Se llevó a cabo un estudio descriptivo retrospectivo en tres centros de alta complejidad en Medellín, Colombia. Se incluyeron adultos con diagnóstico de amiloidosis AL entre 2012 y 2022. Se analizaron datos clínicos, de laboratorio, histológicos, de tratamiento y de supervivencia. Resultados: El estudio incluyó 63 pacientes. La afectación renal fue más prevalente (66%), seguida de la afectación cardíaca (61%). El 61% de los pacientes presentaron afectación multiorgánica. El depósito amiloide se detectó con mayor frecuencia en la biopsia renal (40%). El tratamiento basado en bortezomib se utilizó en el 68%, y el 23.8% recibió altas dosis de quimioterapia con trasplante autólogo de progenitores hematopoyéticos (ADQT-TAPH). Se observó respuesta hematológica en el 95% de los pacientes con datos disponibles. La respuesta de órgano cardíaca y renal fue del 15% y 14%, respectivamente. La mediana de la supervivencia global fue de 45.1 meses (IC del 95%: 22.2-63.8). En el análisis multivariado, la afectación cardíaca se asoció significativamente con una supervivencia global inferior (HR 3.27; IC del 95%: 1.23-8.73; p=0.018), ADQT-TAPH mostró una tendencia no significativa hacia una mejora en la supervivencia global (HR 0.25; IC 95%: 0.06-1.09; p=0.065). Conclusiones: En este estudio de pacientes colombianos con amiloidosis AL, la afectación renal fue más frecuente que la afectación cardíaca. La supervivencia global y la afectación multiorgánica fueron consistentes con datos de otras regiones del mundo. El análisis multivariado identificó la afectación cardíaca y ADQT-TAPH como posibles factores pronósticos.

JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms.

Background: Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia. These diseases are caused by mutations in genes, such as the JAK2, MPL, and CALR genes, which participate in regulating the JAK-STAT signaling pathway. Objective: This study aimed to establish the frequencies of mutations in the JAK2, MPL, and CALR genes in a group of Colombian patients with a negative clinical diagnosis of BCR-ABL chronic myeloproliferative neoplasms. Methods: The JAK2 V617F and MPL W515K mutations and deletions or insertions in exon 9 of the CALR gene were analyzed in 52 Colombian patients with polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Results: The JAK2V617F mutation was carried by 51.9% of the patients, the CALR mutation by 23%, and the MPL mutation by 3.8%; 23% were triple-negative for the mutations analyzed. In these neoplasms, 6 mutation types in CALR were identified, one of which has not been previously reported. Additionally, one patient presented a double mutation in both the CALR and JAK2 genes. Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Conclusion: Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

Antecedentes: Entre las neoplasias mieloproliferativas crónicas no asociadas con mutaciones BCR-ABL se encuentran la policitemia vera, la mielofibrosis primaria y la trombocitemia esencial. Estas enfermedades están causadas por mutaciones en genes, como los genes JAK2, MPL y CALR, que participan en la regulación de la vía de señalización JAK-STAT. Objetivo: Establecer las frecuencias de mutaciones en los genes JAK2, MPL y CALR en un grupo de pacientes colombianos con diagnóstico clínico negativo de NMP BCR-ABL. Metodos: Se analizaron las mutaciones y deleciones o inserciones JAK2 V617F y MPL W515K en el exón 9 del gen CALR en 52 pacientes colombianos con policitemia vera, mielofibrosis primaria y trombocitemia esencial. Resultados: La mutación JAK2V617F la portaban el 51.9% de los pacientes, la mutación CALR el 23.0% y la mutación MPL el 3.8%; El 23.0% fueron triple negativos para las mutaciones analizadas. En estas neoplasias se identificaron seis tipos de mutación en CALR, uno de los cuales no ha sido reportado previamente. Además, un paciente presentó una doble mutación tanto en el gen CALR como en el JAK2. En cuanto a los resultados hematológicos para las mutaciones, se encontraron diferencias significativas en el nivel de hemoglobina, el nivel de hematocrito y el recuento de plaquetas entre las tres neoplasias. Conclusiones: Así, este estudio demuestra la importancia de la caracterización molecular de las mutaciones JAK2, CALR y MPL en pacientes colombianos (cuyo contexto genético aún no está claro en las neoplasias antes mencionadas) para lograr un diagnóstico certero, un buen pronóstico, un manejo adecuado y una mejoría del paciente. supervivencia.

Clinical characterization and outcomes of a cohort of colombian patients with AL Amyloidosis

Background: Amyloid light chain (AL) amyloidosis is characterized by amyloid fibril deposition derived from monoclonal immunoglobulin light chains, resulting in multiorgan dysfunction. Limited data exist on the clinical features of AL amyloidosis. Objective: This study aims to describe the clinical characteristics, treatments, and outcomes in Colombian patients with AL amyloidosis. Methods: A retrospective descriptive study was conducted at three high-complexity centers in Medellín, Colombia. Adults with AL amyloidosis diagnosed between 2012 and 2022 were included. Clinical, laboratory, histological, treatment, and survival data were analyzed. Results: The study included 63 patients. Renal involvement was most prevalent (66%), followed by cardiac involvement (61%). Multiorgan involvement occurred in 61% of patients. Amyloid deposition was most commonly detected in renal biopsy (40%). Bortezomib-based therapy was used in 68%, and 23.8% received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT-ASCT). Hematological response was observed in 95% of patients with available data. Cardiac and renal organ responses were 15% and 14%, respectively. Median overall survival was 45.1 months (95% CI: 22.2-63.8). In multivariate analysis, cardiac involvement was significantly associated with inferior overall survival (HR 3.27; 95% CI: 1.23-8.73; p=0.018), HDCT-ASCT had a non-significant trend towards improved overall survival (HR 0.25; 95% CI: 0.06-1.09; p=0.065). Conclusions: In this study of Colombian patients with AL amyloidosis, renal involvement was more frequent than cardiac involvement. Overall survival and multiorgan involvement were consistent with data from other regions of the world. Multivariate analysis identified cardiac involvement and HDCT-AHCT as possible prognostic factors.

Antecedentes: La amiloidosis por amiloide de cadenas ligeras (AL) se caracteriza por el depósito de fibrillas amiloides derivadas de cadenas ligeras de inmunoglobulinas monoclonales, lo que resulta en disfunción multiorgánica. Existen datos limitados sobre las características clínicas de la amiloidosis AL. Objetivo: Este estudio tiene como objetivo describir las características clínicas, tratamientos y desenlaces en pacientes colombianos con amiloidosis AL. Métodos: Se llevó a cabo un estudio descriptivo retrospectivo en tres centros de alta complejidad en Medellín, Colombia. Se incluyeron adultos con diagnóstico de amiloidosis AL entre 2012 y 2022. Se analizaron datos clínicos, de laboratorio, histológicos, de tratamiento y de supervivencia. Resultados: El estudio incluyó 63 pacientes. La afectación renal fue más prevalente (66%), seguida de la afectación cardíaca (61%). El 61% de los pacientes presentaron afectación multiorgánica. El depósito amiloide se detectó con mayor frecuencia en la biopsia renal (40%). El tratamiento basado en bortezomib se utilizó en el 68%, y el 23.8% recibió altas dosis de quimioterapia con trasplante autólogo de progenitores hematopoyéticos (ADQT-TAPH). Se observó respuesta hematológica en el 95% de los pacientes con datos disponibles. La respuesta de órgano cardíaca y renal fue del 15% y 14%, respectivamente. La mediana de la supervivencia global fue de 45.1 meses (IC del 95%: 22.2-63.8). En el análisis multivariado, la afectación cardíaca se asoció significativamente con una supervivencia global inferior (HR 3.27; IC del 95%: 1.23-8.73; p=0.018), ADQT-TAPH mostró una tendencia no significativa hacia una mejora en la supervivencia global (HR 0.25; IC 95%: 0.06-1.09; p=0.065). Conclusiones: En este estudio de pacientes colombianos con amiloidosis AL, la afectación renal fue más frecuente que la afectación cardíaca. La supervivencia global y la afectación multiorgánica fueron consistentes con datos de otras regiones del mundo. El análisis multivariado identificó la afectación cardíaca y ADQT-TAPH como posibles factores pronósticos.

JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms

Background: Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia. These diseases are caused by mutations in genes, such as the JAK2, MPL, and CALR genes, which participate in regulating the JAK-STAT signaling pathway. Objective: This study aimed to establish the frequencies of mutations in the JAK2, MPL, and CALR genes in a group of Colombian patients with a negative clinical diagnosis of BCR-ABL chronic myeloproliferative neoplasms. Methods: The JAK2 V617F and MPL W515K mutations and deletions or insertions in exon 9 of the CALR gene were analyzed in 52 Colombian patients with polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Results: The JAK2V617F mutation was carried by 51.9% of the patients, the CALR mutation by 23%, and the MPL mutation by 3.8%; 23% were triple-negative for the mutations analyzed. In these neoplasms, 6 mutation types in CALR were identified, one of which has not been previously reported. Additionally, one patient presented a double mutation in both the CALR and JAK2 genes. Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Conclusion: Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

Antecedentes: Entre las neoplasias mieloproliferativas crónicas no asociadas con mutaciones BCR-ABL se encuentran la policitemia vera, la mielofibrosis primaria y la trombocitemia esencial. Estas enfermedades están causadas por mutaciones en genes, como los genes JAK2, MPL y CALR, que participan en la regulación de la vía de señalización JAK-STAT. Objetivo: Establecer las frecuencias de mutaciones en los genes JAK2, MPL y CALR en un grupo de pacientes colombianos con diagnóstico clínico negativo de NMP BCR-ABL. Metodos: Se analizaron las mutaciones y deleciones o inserciones JAK2 V617F y MPL W515K en el exón 9 del gen CALR en 52 pacientes colombianos con policitemia vera, mielofibrosis primaria y trombocitemia esencial. Resultados: La mutación JAK2V617F la portaban el 51.9% de los pacientes, la mutación CALR el 23.0% y la mutación MPL el 3.8%; El 23.0% fueron triple negativos para las mutaciones analizadas. En estas neoplasias se identificaron seis tipos de mutación en CALR, uno de los cuales no ha sido reportado previamente. Además, un paciente presentó una doble mutación tanto en el gen CALR como en el JAK2. En cuanto a los resultados hematológicos para las mutaciones, se encontraron diferencias significativas en el nivel de hemoglobina, el nivel de hematocrito y el recuento de plaquetas entre las tres neoplasias. Conclusiones: Así, este estudio demuestra la importancia de la caracterización molecular de las mutaciones JAK2, CALR y MPL en pacientes colombianos (cuyo contexto genético aún no está claro en las neoplasias antes mencionadas) para lograr un diagnóstico certero, un buen pronóstico, un manejo adecuado y una mejoría del paciente. supervivencia.

Is Your Kid Actin Out? A Series of Six Patients With Inherited Actin-Related Protein 2/3 Complex Subunit 1B Deficiency and Review of the Literature.

BACKGROUND: Hereditary actin-related protein 2/3 complex subunit 1B deficiency is characterized clinically by ear, skin, and lung infections, bleeding, eczema, food allergy, asthma, skin vasculitis, colitis, arthritis, short stature, and lymphadenopathy. OBJECTIVE: We aimed to describe the clinical, laboratory, and genetic features of six patients from four Mexican families. METHODS: We performed exome sequencing in patients of four families with suspected actinopathy, collected their data from medical records, and reviewed the literature for reports of other patients with actin-related protein 2/3 complex subunit 1B deficiency. RESULTS: Six patients from four families were included. All had recurrent infections, mainly bacterial pneumonia, and cellulitis. A total of 67% had eczema whereas 50% had food allergies, failure to thrive, hepatomegaly, and bleeding. Eosinophilia was found in all; 84% had thrombocytopenia, 67% had abnormal-size platelets and anemia. Serum levels of IgG, IgA, and IgE were highly increased in most; IgM was normal or low. T cells were decreased in 67% of patients, whereas B and NK cells were increased in half of patients. Two of the four probands had compound heterozygous variants. One patient was successfully transplanted. We identified 28 other patients whose most prevalent features were eczema, recurrent infections, failure to thrive, bleeding, diarrhea, allergies, vasculitis, eosinophilia, platelet abnormalities, high IgE/IgA, low T cells, and high B cells. CONCLUSION: Actin-related protein 2/3 complex subunit 1B deficiency has a variable and heterogeneous clinical spectrum, expanded by these cases to include keloid scars and Epstein-Barr virus chronic hepatitis. A novel deletion in exon 8 was shared by three unrelated families and might be the result of a founder effect.

EuroMed Cancer Network contributions to eliminating cervical cancer in low- and middle-income Mediterranean countries.

Background: Cervical cancer places a significant burden on low- and middle-income countries (LMICs). The EuroMed Cancer Network (EuMedCN) brings together cancer experts and stakeholders from the Mediterranean countries to promote sustainable cancer screening and support implementation of the WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Aim: To highlight the constructive role of EuMedCN in mitigating inequalities in access to cervical cancer prevention and screening across the Mediterranean LMICs. Methods: Through its workshops and meetings, EuMedCN members discussed new developments in cancer prevention and control, and how best to translate the WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem into public health policies in the Mediterranean LMICs. This led to targeted actions in the selected countries. Results: Seven priority actions were implemented to improve cervical cancer screening in the Mediterranean LMICs. EuMedCN supported organized screening, new pilot technologies and enhancement of evaluation systems. Integrating cervical cancer screening into other disease programmes and fostering multidisciplinary networks were promoted as key to achieving targets of the WHO global strategy. Conclusion: International networks, such as EuMedCN, have the potential to bring together experts and stakeholders to share experiences and catalyse resource mobilization. They can support affordable and synergistic solutions for cervical cancer prevention.

Not enough by half: NFAT5 haploinsufficiency in two patients with Epstein-Barr virus susceptibility.

Introduction: The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals. Objective: We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology. Methods: After informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells. Results: We describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis. Discussion: NFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease.

Anaphylaxis to SARS-CoV-2 Vaccines in the Setting of a Nationwide Passive Epidemiological Surveillance Program.

BACKGROUND: Information on anaphylaxis among recipients of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains scarce. OBJECTIVE: To identify the observed incidence of anaphylaxis in recipients of different anti-SARS-CoV-2 vaccines. METHODS: A nationwide observational study among recipients of 61,414,803 doses of seven different anti-SARS-CoV-2 vaccines, describing the incidence and characteristics of adult patients (age ≥ 18 years) who developed anaphylaxis as an adverse event following immunization (AEFI) against SARS-CoV-2 vaccines between December 24, 2020, and October 15, 2021, in Mexico. RESULTS: Sixty-six patients developed anaphylaxis as an AEFI, for an overall observed incidence of 1.07 cases per 1,000,000 (95% CI 0.84-1.37) administered doses. Eighty-six percent of the patients were female, consistent with previous reports of AEFI to COVID-19 vaccines. mRNA-based vaccine recipients had the highest frequency of anaphylaxis, followed by adenovirus-vectored vaccines and inactivated virus recipients, with an observed incidence of 2.5, 0.7, and 0.2 cases per 1,000,000 doses administered, respectively. Only 46% of the patients received correct treatment with epinephrine as the first-line treatment through the appropriate route and dose. We detected one case of anaphylactic reaction-related death occurring 5 min following immunization with ChAdOx1 nCov-19 for a mortality rate of 1.5% among those who developed this AEFI. CONCLUSIONS: In our population, anaphylactic reactions were infrequent. Our study provides further evidence supporting the security of these newly developed vaccines.

Agreement between the Clinical and Autopsy Results of Children Who Died with Pneumonia in Pediatric Intensive Care.

This study aimed to measure the agreement between the clinical and anatomopathological results of children who died with pneumonia from two pediatric intensive care units. Pediatric patients chosen were those who died between January 2008 and December 2015. The agreement was tested with Kappa. A total of 111 autopsies were included. Upon autopsy, 58 had pneumonia, 33 had it clinically and pathologically, 24 only clinically, and one only in autopsy. The Kappa agreement was 0.5 (95% confidence interval of 0.4 to 0.7). The level of agreement between the clinic and the autopsy is moderate. However, the consistency in cases of clinical pneumonia is low.

Erdheim-Chester disease: First pediatric case report in Colombia / Enfermedad de Erdheim-Chester: primer caso pediátrico reportado en Colombia

The Erdheim-Chester's disease is extremely rare in children. We present the case of a 12-year-old girl with histological and radiological diagnosis of this disease and mutation of the BRAF gene, who developed multisystemic compromise requiring treatment with dabrafenib. We identified 22 reports of this condition among children worldwide and this is the second pediatric case in Latin America. Diagnostic imaging is critical to confirm Erdheim-Chester disease and for the surgical planning of the biopsy. Additionally, we identified the parasellar dark sign, which has previously been reported on lymphocytic hypophysitis. This report contributes to the current practice as it shows the clinical presentation and the diagnostic workout of this disease in pediatrics.

La enfermedad de Erdheim-Chester es una condición extremadamente rara en la edad pediátrica. Se presenta el caso de una niña de 12 años con diagnóstico histológico y radiológico de enfermedad de Erdheim-Chester multisistémica y mutación en el gen BRAF, que requirió tratamiento con dabrafenib. Hasta el momento, se han reportado 22 casos pediátricos en el mundo y este es el segundo en Latinoamérica. Se observó el hallazgo radiológico denominado signo oscuro paraselar, descrito hasta ahora en pacientes con hipofisitis autoinmunitaria para diferenciarlos de aquellos con adenomas hipofisarios. Este reporte contribuye a la literatura médica en dos aspectos fundamentales: las manifestaciones clínicas de la enfermedad y su diagnóstico en la población pediátrica.

Enfermedad de Erdheim-Chester: primer caso pediátrico reportado en Colombia / Erdheim-Chester disease: First pediatric case report in Colombia

Resumen | La enfermedad de Erdheim-Chester es una condición extremadamente rara en la edad pediátrica. Se presenta el caso de una niña de 12 años con diagnóstico histológico y radiológico de enfermedad de Erdheim-Chester multisistémica y mutación en el gen BRAF, que requirió tratamiento con dabrafenib. Hasta el momento, se han reportado 22 casos pediátricos en el mundo y este es el segundo en Latinoamérica. Se observó el hallazgo radiológico denominado signo oscuro paraselar, descrito hasta ahora en pacientes con hipofisitis autoinmunitaria para diferenciarlos de aquellos con adenomas hipofisarios. Este reporte contribuye a la literatura médica en dos aspectos fundamentales: las manifestaciones clínicas de la enfermedad y su diagnóstico en la población pediátrica.

Abstract | The Erdheim-Chester's disease is extremely rare in children. We present the case of a 12-year-old girl with histological and radiological diagnosis of this disease and mutation of the BRAF gene, who developed multisystemic compromise requiring treatment with dabrafenib. We identified 22 reports of this condition among children worldwide and this is the second pediatric case in Latin America. Diagnostic imaging is critical to confirm Erdheim-Chester disease and for the surgical planning of the biopsy. Additionally, we identified the parasellar dark sign, which has previously been reported on lymphocytic hypophysitis. This report contributes to the current practice as it shows the clinical presentation and the diagnostic workout of this disease in pediatrics.

[Causes and treatment of anaphylaxis in a Mexican third-level pediatric hospital]. / Causas y tratamiento de anafilaxia en un hospital pediátrico mexicano de tercer nivel.

OBJECTIVE: To clinically characterize the events of anaphylaxis in a third-level pediatric hospital. METHODS: 1148 clinical records were reviewed. Eventually, the information of 35 events of anaphylaxis in 20 patients was analyzed; three of them had multiple episodes of anaphylaxis. RESULTS: The median age for the anaphylactic episodes was 11 years (Interquartile range 10 years, Q1 = 5, Q3 = 15), predominantly in adolescents between the ages of 12 and 17 years, and there was a slight predominance in women. The most frequent clinical manifestations were cutaneous (86%), followed by respiratory (83%), cardiovascular (74%), and gastrointestinal (46%) alterations. Cardiac arrest was documented in three episodes; however, no anaphylaxis-related deaths were reported. The main triggers for anaphylaxis were food (34%), medications (29%), allergen-specific immunotherapy (14%), and latex (11%). In patients with perioperative anaphylaxis, the clinical behavior was severe. Epinephrine was administered in 27 out of the 35 events (77%), but only in 11 cases it was the first-line treatment. Systemic corticosteroids were the most frequently used treatment, followed by epinephrine and antihistamines. CONCLUSIONS: The use of epinephrine, which is the mainstay of the treatment, is suboptimal; with a preferred use of second-line medications like corticosteroids. Clear protocols for the diagnosis and treatment of anaphylaxis, as well as continuous education of health personnel, are necessary.

Objetivo: Caracterizar clínicamente los eventos de anafilaxia en un hospital pediátrico de tercer nivel. Métodos: Se revisaron 1148 expedientes clínicos. Finalmente, se analizó la información correspondiente a 35 episodios de anafilaxia en 20 pacientes; tres de ellos con múltiples episodios de anafilaxia. Resultados: La edad mediana de los episodios de anafilaxia fue de 11 años (rango intercuartilar 10 años, Q1 = 5, Q3 = 15), con predomino en adolescentes de 12 a 17 años y del sexo femenino. Las manifestaciones clínicas más frecuentes fueron las cutáneas (86 %), seguidas de las respiratorias (83 %), las cardiovasculares (74 %) y las gastrointestinales (46 %). En tres casos se documentó paro cardiorrespiratorio, pero no hubo casos de mortalidad asociada a anafilaxia. Los principales desencadenantes fueron alimentos (34 %), medicamentos (29 %), inmunoterapia para alérgenos (14 %) y látex (11 %). En los pacientes con anafilaxia perioperatoria el comportamiento clínico fue grave. La adrenalina se utilizó en 27 de los 35 episodios (77 %), en 11 de ellos fue el tratamiento de primera elección. Los corticosteroides sistémicos fueron los medicamentos más frecuentemente utilizados, seguidos de la adrenalina y los antihistamínicos. Conclusiones: El uso de adrenalina, pilar del tratamiento de anafilaxia, es subóptimo; con uso preferente de medicamentos de segunda línea como los corticosteroides. Se requieren protocolos para diagnóstico y tratamiento de anafilaxia, aunado a una educación continua del personal de salud.

COVID-19 in the Context of Inborn Errors of Immunity: a Case Series of 31 Patients from Mexico.

INTRODUCTION: Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe SARS-CoV-2 infection, the reported impact of COVID-19 in these patients has been reassuring, while the differential susceptibility of distinct types of IEI remains unclear. OBJECTIVE: We aimed to describe the findings and outcomes of our known patients with IEI who were diagnosed with COVID-19. METHODS: In a retrospective study from March 2020 to February 2021, four centers in Mexico collected clinical, laboratory, and genetic data from pediatric and adult patients with known diagnoses of IEI who presented with COVID-19, based on compatible symptoms and positive SARS-CoV-2 testing or known household exposure. RESULTS: We report 31 patients with known IEI from Mexico who presented with SARS-CoV-2 infection. Seventy-four percent were male, 52% were pediatric, and 81% survived. Their ages ranged from 5 months to 56 years, with a median of 17 years. Sixty-five percent had predominant antibody deficiencies, 48% were hospitalized, and 26% required ICU. Pediatric patients had a higher hospital admission rate than adults. Inpatient mortality was 40%, and ICU mortality rate was 63%. Forty-eight percent developed pneumonia, while 36% had evidence of hyperinflammation (4 adults and 7 children). Predominant laboratory features were lymphopenia and thrombocytopenia, seen in 70 and 44% of patients, respectively. The serum D-dimer median value was 2.6 (0.5-20.6) µg/mL, and the median highest ferritin value was 1015 (32-10,303) ng/mL. Intravenous immunoglobulin was used in 80% of patients. Other treatments included macrolides (39%) and corticosteroids (29%). Six patients died from secondary infection or uncontrolled systemic inflammation. DISCUSSION: Although impaired immunity due to IEI may be a predisposing factor for severe COVID-19, most of our patients with IEI who acquired the SARS-CoV-2 infection developed a well-tolerated infection and survived, as have more than 80% of worldwide reported patients to date. An impaired immune or inflammatory response may be a predisposing factor for some and a protective factor for others. A systematic review of the literature could help identify those patients at risk of severe disease and complications. Healthcare-associated infections should be aggressively prevented.

Diagnostic and therapeutic caveats in Griscelli syndrome.

Griscelli syndrome (GS) is a rare autosomal recessive disease with characteristic pigment distribution, and there are currently 3 types according to the underlying genetic defect and clinical features. We present the case of a girl born from consanguineous parents who presented with predominant neurologic symptoms, silvery hair and granulomatous skin lesions. Cerebral magnetic resonance revealed diffuse white matter lesions, and central nervous system (CNS) lymphocytic infiltration was suspected. The patient underwent haematopoietic stem cell transplantation with graft failure and autologous reconstitution. She developed elevated liver enzyme with a cholestatic pattern. Multiple liver biopsies revealed centrilobular cholestasis and unspecific portal inflammation that improved with immunomodulatory treatment. She was revealed to have an impaired cytotoxicity in NK cells and a decreased expression of RAB27A. However, no variants were found in the gene. All types of GS present with pigment dilution and irregular pigment clumps that can be seen through light microscopy in hair and skin biopsy. Dermic granulomas and immunodeficiency with infectious and HLH predisposition have been described in GS type 2 (GS2). Neurologic alterations might be seen in GS type 1 (GS1) and GS type 2 (GS2), due to different mechanisms. GS1 presents with neurologic impairment secondary to myosin Va role in neuronal development and synapsis. Meanwhile, GS2 can present with neurologic impairment secondary to SNC HLH. Clinical features and cytotoxicity might aid in differentiating GS1 and GS2, especially since treatment differs.