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.

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.

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.

Kawasaki disease mimickers.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects patients younger than 5 years. In the absence of an available, affordable diagnostic test, detailed clinical history and physical examination are still fundamental to make a diagnosis. METHODS: We present five representative cases with KD-like presentations: systemic onset juvenile idiopathic arthritis, mycoplasma-induced rash and mucositis, staphylococcal scalded skin syndrome, BCGosis, and the recently described multisystemic inflammatory syndrome in children (MIS-C) associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus. RESULTS: Rash, fever, and laboratory markers of inflammation can be present in several childhood diseases that may mimic KD. CONCLUSION: The term 'Kawasaki syndrome' instead of 'Kawasaki disease' may be more appropriate. Physicians should consider an alternative diagnosis that may mimic KD, particularly considering MIS-C during the present pandemic, as an aggressive diagnostic and therapeutic approach is needed.

Meta-analysis of hematopoietic stem cell transplantation in major histocompatibility complex class II deficiency.

Major histocompatibility complex class II deficiency is a rare case of PID. Specific recommendations for hematopoietic stem cell transplant, the only curative treatment option, are still lacking. This meta-analysis aims to identify the factors associated with better prognosis in these patients. Thirteen articles reporting 63 patients with major histocompatibility complex class II deficiency that underwent hematopoietic stem cell transplant were included. The median age for hematopoietic stem cell transplant was 18 months. The most common source of transplant was bone marrow, with alternative sources as umbilical cord blood emerging during recent years. The highest proportion of engraftment was seen with umbilical cord. Engraftment was higher in patients with matched donors, with better overall survival in patients with reduced-intensity conditioning. Graft-vs-host disease developed in 65% of the patients, with grades I-II being the most frequently encountered. There was a higher mortality in patients with myeloablative conditioning and no engraftment. There was an inverse correlation between survival and stage of graft-vs-host disease. The main cause of mortality was infectious disease, mostly secondary to viral infections. Ideally, matched grafts should be used, and reduced-intensity conditioning should be considered to reduce early post-transplant complications. GVHD and viral prophylaxis are fundamental.

Características clínicas y microbiológicas de las infecciones de piel y tejidos blandos por Staphylococcus aureus en niños de un hospital en Medellín durante los años 2013 a 2015 / Clinical and microbiological characteristics of skin and soft tissue infections caused by Staphylococcus aureus in children in a hospital in Medellin from 2013 to 2015

Resumen Introducción: El principal microorganismo implicado en las infecciones de piel y tejidos blandos (IPTB) es Staphylococcus aureus, con incremento en las cepas resistentes a meticilina en los últimos años. Objetivo: Identificar la frecuencia de S. aureus resistente a meticilina (SARM) en IPTB en niños que consultaron a un hospital de cuarto nivel en la ciudad de Medellín. Métodos: Estudio descriptivo, retrospectivo, a partir de la revisión de historias clínicas. Se incluyeron pacientes menores de 18 años con IPTB causadas por S. aureus que no cumplieran con criterios de enfermedad invasora. Resultados: La prevalencia de SARM en esta población fue de 31%. El principal diagnóstico fue absceso cutáneo (68%), seguido por infección de sitio quirúrgico (15%) y celulitis no purulenta (6%). Tenían alguna co-morbilidad 85% de los pacientes. Todos los aislados fueron sensibles a rifampicina y cotrimoxazol. Ocho por ciento de los aislados fueron resistentes a clindamicina. Se encontró mayor prevalencia de SARM en lactantes comparado con los mayores de 2 años (60 vs 23%, p = 0,0109). Conclusión: Ante la alta prevalencia de SARM en IPTB se recomienda incluir en el tratamiento empírico antimicrobianos con cobertura para estas cepas, principalmente para lactantes.

Background: Skin and soft tissue infections (SSTI) are very common in children and Staphylococcus aureus is the main agent, with an increase of methicillin resistant strains (MRSA) in recent years. Aim: To identify the frequency of MRSA in skin and soft tissue infections (SSTI) in children from a high complex hospital in Medellin, Colombia. Methods: This is a descriptive, retrospective study, information was obtained from medical records. We included patients younger than 18 years with SSTI due to S. aureus who did not meet criteria for invasive disease. Results: The prevalence of MRSA in this population was 31%. The main diagnosis was cutaneous abscess (68%), followed by surgical site infection (15%) and non-purulent cellulitis (6%). Eighty five percent of the patients had at least 1 comorbidity. All isolates were sensitive to rifampicin and cotrimoxazole and 8% of the isolates were resistant to clindamycin. There was a higher prevalence of MRSA in patients under 2 years compared to older (60 vs 23%, p = 0,0109). Conclusion: In view of the high prevalence of MRSA in SSTI, empirical treatment with adequate coverage for MRSA is recommended, especially for patients under 2 years of age.

Reporte de caso de transmisión vertical de la infección por virus chikungunya / Vertical transmission of chikungunya virus infection: case report

La infección por virus chikungunya es una enfermedad transmitida por vectores, que en los años 2005-2006 se describió la transmisión vertical, con una tasa de infección en el recién nacido hasta del 49% en madres con presencia de viremia durante el parto. Puede presentar manifestaciones clínicas graves en los neonatos y potenciales secuelas en el neurodesarrollo. OBJETIVO: Presentar un caso de infección por virus chikungunya vertical y revisión de la literatura disponible. CASO CLÍNICO: Recién nacido de sexo femenino que inició con fiebre y exantema durante la primera semana de vida, posteriormente con elevación de transaminasas y trombocitopenia, con el antecedente de un cuadro clínico en la madre de síntomas compatibles con infección por chikungunya el día del parto. Se documentaron anticuerpos tipo IgM específicos para chikungunya que establecieron el diagnóstico. CONCLUSIONES: Dada la alta tasa de transmisibilidad perinatal de la infección por virus chikungunya, este diagnóstico debe considerarse en todo recién nacido hijo de madre con síntomas sugestivos de la infección en el período cercano al parto.

Chikungunya virus infection is a disease transmitted by vectors, in which vertical transmission was described in years 2005-2006. An infection rate up to 49% in neonates born from mothers with active viremia during labor has been observed. Perinatal infection could results in serious complications and potential cognitive impairment. OBJECTIVE: To describe a newborn with Chikungunya virus infection secundary to vertical transmission. CLINICAL CASE: A female newborn is analyzed. She presented with fever and exanthema during her first week of life, elevation of transaminases and thrombocytopenia. Her mother had had symptoms compatible with chikungunya virus infection on the day of the delivery. Specific IgM antibodies against chikungunya were documented and the diagnosis was confirmed. CONCLUSION: Given the high perinatal transmissibility rate of chikungunya virus, this diagnosis should be considered in every newborn child of a mother with suggestive symptoms of chikungunya in the days surrounding delivery.

Estridor en neonatos con encefalopatía hipóxica sometidos a hipotermia terapéutica / Stridor in neonates with hypoxic encephalopathy undergoing therapeutic hypothermia

Resumen Introducción: la hipotermia terapéutica para el tratamiento de la encefalopatía hipóxico isquémica ha demostrado reducción en la mortalidad y secuelas neurológicas, dentro de los eventos adversos asociados a esta terapia se ha descrito la presencia de estridor. Objetivo: describir las características y la incidencia de estridor en un grupo de neonatos sometidos a hipotermia terapéutica para encefalopatía hipóxica. Resultados: en 34 neonatos con encefalopatía hipóxico isquémica sometidos a terapia con hipotermia en una unidad neonatal, se encontró predominio del sexo masculino y de encefalopatía hipóxico isquémica clasificación Sarnat II, de los cuales 12 neonatos (35.3 %) presentaron estridor. En total 7 de los 34 pacientes recibieron esteroide previo a la extubación y sólo 1 de ellos presentó estridor (14 %). Los pacientes que no recibieron esteroide previo a la extubación presentaron estridor en 40 % de los casos. De los pacientes que desarrollaron estridor, el 33 % requirió intubación por esta causa. Conclusiones: nuestra serie de casos no encontró diferencias con el uso de adrenalina o esteroides previo a la extubación para la prevención de estridor en pacientes con hipotermia; además se presentaron 2 casos de estridor en pacientes sin manipulación previa de la vía aérea, lo que soporta que el mecanismo inflamatorio no es el único involucrado en el estridor en los pacientes sometidos a hipotermia terapéutica.

Summary Introduction: Therapeutic hypothermia used for term and late preterm newborns with hypoxic ischemic encephalopathy has shown decrease in mortality and neurocognitive impairment, stridor has been recently described as an adverse effect of this therapy. Results: In 34 newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia in a neonatal unit, we found male sex and Sarnat II hypoxic encephalopathy predominance, 12 patients (35.3%) developed stridor. 7 out of the 34 patients received steroid therapy previous to extubation and only 1 (14%) presented stridor. The patients that didn't received steroids 40% presented stridor. Out of the patients that developed stridor 33% required intubation because of this cause. Conclusion: Our series didn't find difference in the use of adrenaline or steroids previous to extubation to prevent stridor in hypothermic patients. We also had 2 cases that developed stridor without airway manipulation, these supports that inflammatory mechanism is not the only one involved in the development of stridor in newborns under cooling therapy.

Alergia a fórmula de aminoácidos libres en síndrome de intestino corto: Reporte de 2 casos / Two Case Reports of Allergies to Amino Acid Based Formula in Patients with Short Bowel Syndrome

El síndrome de intestino corto constituye una entidad con alteración en la superficie de absorción y en la funcionalidad del sistema gastrointestinal. En estos pacientes se ha descrito mayor predisposición de alergias alimentarias a la proteína de la leche de vaca y al huevo. Se describen los casos de 2 lactantes menores con síndrome de intestino corto y reacciones alérgicas a fórmulas de aminoácidos libres. En el primer caso la paciente presentó una respuesta no mediada por inmunoglobulina E (IgE) manifestada clínicamente con una colitis eosinofílica, que mejoró con uso de esteroides sistémicos, cambio a otra fórmula elemental. En el segundo caso se presenta una paciente con intolerancia inicial a la leche materna y fórmula extensamente hidrolizada. Con primera fórmula de aminoácidos libres presenta sangrado gastrointestinal y manifestaciones cutáneas, por lo que se hace cambio a otra fórmula de aminoácidos libres con tolerancia transitoria. Subsecuentemente, en el contexto de un cuadro viral no especificado con compromiso respiratorio y gastrointestinal, presenta reacción anafiláctica a la fórmula de aminoácidos libres que venía tolerando previamente, por lo que se hace necesario cambio a dieta modular con tolerancia adecuada. No se encontraron reportes previos en la literatura de reacciones alérgicas a fórmulas elementales a base de aminoácidos, por lo cual se reportan los casos descritos. Aún no hay consenso en cuanto a la fórmula ideal para iniciar la alimentación en los pacientes con intestino corto para evitar sensibilización alergénica.

Short bowel syndrome (SBS) is characterized by alterations in the absorption surface and in the functionality of the gastrointestinal system. Patients with SBS are more prone to allergies the protein in cow's milk and eggs. We report two cases of infants with SBS and allergic reactions to amino acid based formulas. In the first case, the patient's response was not IgE-mediated. It manifested clinically with eosinophilic colitis that improved with the use of systemic steroids and a change to another elemental formula. In the second case, the patient initially presented intolerance to breast milk and extensively hydrolyzed formula. After feeding with the first free amino acid formula, the patient developed gastrointestinal bleeding and skin manifestations. Another free amino acid formula was substituted. The patient had transient tolerance to the new formula. Later, in the context of an unspecified viral infection with respiratory and gastrointestinal involvement, the patient presented an anaphylactic reaction to the formula which had previously been tolerated. This necessitated a change to a modular diet which was adequately tolerated. We have presented this case report because no previous reports were found in the literature about allergic reactions to basic amino acid-based formulas. There is still no consensus on the ideal formula for preventing allergic sensitization in patients with SBS.