Variants in CASP10, a diagnostic challenge: Single center experience and review of the literature.

Autoimmune lymphoproliferative syndrome is a primary immunodeficiency caused by variants in FAS-mediated apoptosis related genes and is characterized by lymphadenopathy, splenomegaly and autoimmunity. A total of six different variants in CASP10 have been described as potential causative of disease, although two of them have recently been considered polymorphisms. The high allele frequency of these variants in healthy population in addition to the broad clinical spectrum of the disease difficult the interpretation of their pathogenicity. Here, we describe the clinical and analytical findings of three new patients carrying variants in CASP10 and summarize 12 more cases from the literature. Autoimmune cytopenias, adenopathies and increment of TCRαß+CD4-CD8- cells have been the most common findings, being possibly the FAS-mediated apoptosis pathway the pathogenic mechanism of this disease. The clinical impact and the consequences of CASP10 variants are not fully elucidated, therefore the description of new cases will contribute to solve this issue.

Mucositis Secondary to Chlamydia pneumoniae Infection: Expanding the Mycoplasma pneumoniae-Induced Rash and Mucositis Concept.

The term Mycoplasma pneumoniae-induced rash and mucositis (MIRM) was recently proposed to identify the mucocutaneous condition secondary to M. pneumoniae infection that had historically been regarded among the more confusing pathologies of erythema multiforme and Stevens-Johnson syndrome. Based on a number of previous reports, these syndromes require differentiation since they have different prognoses and specific treatment requirements. We report a case of oral and genital erosions that strongly resembled MIRM without rash but were found to be secondary to a Chlamydia pneumoniae infection. After a thorough review of the literature on this subject, we propose that C. pneumoniae should also be considered a potential causative agent of MIRM and that this term should be amended to include C. pneumoniae infection.

Tuberculosis in infants less than 3 months of age. / Tuberculosis en lactantes menores de 3 meses.

A review was conducted on infants less than 3 months of age diagnosed with tuberculosis between 1978 and 2014. Eight patients were diagnosed (1.4% of paediatric tuberculosis cases): 3 confirmed congenital tuberculosis, 3 suspected (endometrial biopsy was not performed), and 2 postnatal tuberculosis. Tuberculin skin test was negative in two patients. Diagnostic performance of culture (7/7, 100%) and PCR (3/3, 100%) of gastric aspirates was higher than that of acid-fast bacilli smears (5/8, 62%) and IGRA test (1/3, 33%). Three patients developed miliary disease, and one died. In conclusion, tuberculosis in this age group is rare, severe, and difficult to diagnose. In cases lacking known postnatal contacts, maternal genital tuberculosis should be ruled out by endometrial biopsy.

Identifying priorities to improve paediatric in-hospital antimicrobial use by cross-sectional evaluation of prevalence and appropriateness of prescription.

INTRODUCTION: Information about paediatric in-hospital antimicrobial usage and prescribing patterns to guide improvement strategies is scant. We aim to use an evaluation of the prevalence and appropriateness of antimicrobial prescription to identify antimicrobial stewardship priorities in children. METHODS: A cross-sectional point study was performed on hospitalised paediatric patients in a Spanish tertiary hospital, assessing the prevalence of antimicrobial prescription (PAP) and appropriateness of antimicrobial prescription (AAP). AAP was defined as a correct indication plus an appropriate prescribing pattern (dose, spectrum and interval). Evaluation was performed using established antimicrobial guidelines. Other factors that may have a bearing on antimicrobial prescription were also analysed. RESULTS: A total of 171 patients were included. PAP was 49.7% (85/171) and AAP was 60.9% (91/161). The most common indications for antimicrobial use were antimicrobial prophylaxis (28.3%, 32/113) and pneumonia (8.2%, 8/113). Overall, 161 antimicrobials were prescribed (1.9 antimicrobials per patient): 55.3% (89/161) were empiric, 16.1% (26/161) were targeted and 28.6% (46/161) were prophylactic. Amoxicillin/clavulanate (8.2%, 14/171) and sulfamethoxazole/trimethoprim (8.2%, 14/171) were the most prescribed antimicrobials. The prescription of antifungals (11.7%, 20/171) and antivirals (1.8%, 3/171) was analysed. Major causes of inappropriate antibiotic use were prolonged prescriptions (21.7%, 35/161) and use of agents with an excessively broad coverage spectrum (21.1%, 34/161). PAP and AAP varied between wards and antimicrobials. CONCLUSIONS: Measurement of PAP and AAP offers valuable information for detecting priorities in hospital settings and monitoring antimicrobial usage prior to the development of antimicrobial stewardship programmes. In our setting, the main areas for improvement are duration of therapy and proper use of broad-spectrum antimicrobials.

Consensus document of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Association of Pediatrics for vaccination of immunosuppressed individuals.

The number of people with immunosuppression is increasing considerably due to their greater survival and the use of new immunosuppressive treatments for various chronic diseases. This is a heterogeneous group of patients in whom vaccination as a preventive measure is one of the basic pillars of their wellbeing, given their increased risk of contracting infections. This consensus, developed jointly by the Sociedad Española de Infectología Pediátrica (Spanish Society of Pediatric Infectious Diseases) and the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Paediatrics), provides guidelines for the development of a personalised vaccination schedule for patients in special situations, including general recommendations and specific recommendations for vaccination of bone marrow and solid organ transplant recipients, children with inborn errors of immunity, oncologic patients, patients with chronic or systemic diseases and immunosuppressed travellers.

Safety and Experience With Combined Antiretroviral Prophylaxis in Newborn at High-risk of Perinatal HIV Infection, in a Cohort of Mother Living With HIV-infant Pairs.

BACKGROUND: Perinatal transmission of HIV has dramatically decreased in high-income countries in the last few years with current rates below 1%, but it still occurs in high-risk situations, mainly pregnant women with late diagnosis of infection, poor antiretroviral adherence and a high viral load (VL). In these high-risk situations, many providers recommend combined neonatal prophylaxis (CNP). Our aim was to evaluate the safety and toxicity of CNP in infants deemed at high-risk of HIV infection among mother-infant pairs in the Madrid Cohort. MATERIALS AND METHODS: Prospective, multicenter, observational cohort study between years 2000 and 2019. The subgroup of newborns on CNP and their mothers were retrospectively selected (cohort A) and compared with those who received monotherapy with zidovudine (cohort B). Infants with monotherapy were classified according to treatment regimes in long (6 weeks) and short (4 weeks) course. RESULTS: We identified 227 newborns (33.3% preterm and 7 sets of twins) with CNP. A maternal diagnosis of HIV-1 infection was established during the current pregnancy in 72 cases (36.4%) and intrapartum or postpartum in 31 cases (15.7%). Most infants received triple combination antiretroviral therapy (65.6%; n = 149). The perinatal transmission rate in cohort A was 3.5% (95% confidence interval: 1.13%-5.92%). Infants from cohort A developed anemia (26.1% vs. 19.4%, P = 0.14) and neutropenia more frequently at 50-120 days (21.4% vs. 10.9%, P < 0.01), without significant differences in grade 3 and 4 anemia or neutropenia between the two cohorts. There were no differences in increased alanine aminotransferase. Neutropenia was more common in the long zidovudine regimes. CONCLUSIONS: Our findings provide further evidence of the safety of CNP in infants with high-risk of HIV-1 perinatal transmission.

A mutation in the promoter region of BTK causes atypical XLA.

X-linked Agammaglobulinemia is a primary immunodeficiency caused by mutations in BTK, a tyrosine kinase essential for B lymphocytes differentiation. Patients usually have very low or absent B lymphocytes and are not able to develop humoral specific responses. Here we present a boy, diagnosed with XLA due to a mutation on the promoter region of the gene, whose phenotype is characterised by low percentage of B cells, hypogammaglobulinemia, oscillating neutropenia, antibodies responses to some antigens after vaccination and IgE-mediated allergy. Additional technology as flow cytometry was needed to demonstrate the pathological status of the variant. We focus on the idea that XLA should be suspected in males with B lymphopenia and hypogammaglobulinemia, even if they make humoral specific responses. We also highlight the importance of sequencing BTK's promoter region, as mutations on it can be disease-causing.

Pediatric Asthma and Viral Infection. / Asma y virus en el niño.

Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma.