SARS-CoV-2 seroprevalence among children in Greece during Omicron variant period.

The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. This study aims to evaluate SARS-CoV-2 seroprevalence in children during the different variants' subperiods. A prospective multicenter seroprevalence study was conducted in 7 University public hospitals in Greece from November 2021 to August 2022 (3 subperiods: November 2021-February 2022, March 2022-May 2022, June 2022-August 2022). Children from different age groups, admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 were enrolled. Neutralizing antibodies (Nabs), anti-Spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 IgG in serum were evaluated. A total of 2127 children (males:57,2%; median age:4,8years) were enrolled. Anti-N IgG seropositivity increased from 17,8% in the first sub-period to 40,7% in the second sub-period and then decreased in the third sub-period (36,7%). Anti-S IgG seropositivity appeared to have an increasing trend over the study period, starting from 34,8% and reaching 80,7%. Children aged 1-4 years old have significantly higher anti-N IgG titers compared to children aged 0-1 years old (p < 0,001). Infants have significantly lower anti-S IgG titers compared to all other age groups (p < 0,001). Immunocompromised children and infants have the lowest seropositivity for NAbs.Conclusions During the Omicron period, seropositivity significantly increased, as a result of higher transmissibility. Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1-4 years old present higher antibody titers, suggesting that this age group may mount a higher antibody response. Continuous surveillance seroprevalence studies are needed in children, in order to identify the true extent of SARS-CoV-2 and guide the planning of adequate public health measures.

WHAT IS KNOWN: • Seroprevalence surveys among children may be extremely useful, in order to properly monitor the immunity, either natural or acquired, through the quantification of IgG antibodies and to plan further immunization policies. • There are variations in the seroprevalence of COVID-19 between the different periods, according to the vaccination rates, the type of circulating variant and the transmissibility of the virus. • The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. WHAT IS NEW: • In this large multicenter seroepidemiological study, SARS-CoV-2 seroprevalence rate in children is higher during the Omicron period in comparison to the previous pandemic waves, due to the high transmissibility of the virus and the increased rates of reinfection. • Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1­4 years old present higher antibody titers, indicating that the children of this age group mount a higher antibody response. • This study provides essential information about immunity and the level of protection in the pediatric population, as neutralizing antibodies were evaluated, in addition to the anti-N and anti-S IgG antibodies.

Influenza and Pertussis Vaccine Uptake during Pregnancy: Determinants Found through a Multi-Center Questionnaire Study of Pregnant Women and Healthcare Professionals.

The objective of this article is to assess the adherence of pregnant women to the national recommendations for influenza and pertussis vaccination and the reasons behind their non-adherence. This was a retrospective observational study conducted in a well-defined puerperant population of adequate healthcare standards from December 2018 to December 2019. The study was carried out with 1006 puerperants and 66 health care practitioners. Data were collected, including demographic-obstetric features of pregnant women, whether they received antenatal vaccination, the reasons for having been vaccinated or not as well as health professional's opinion regarding antenatal immunization. The uptake of influenza and pertussis vaccine during pregnancy was suboptimal with lack of recommendation of the vaccine by the healthcare providers being the main barrier. Factors positively associated with antenatal vaccination against influenza were higher level of maternal education and advanced maternal age while antenatal vaccination against pertussis was positively associated with higher level of maternal education. This large-scale retrospective study reveals the inadequacy of antenatal vaccination rates against pertussis and influenza in Crete, Greece. Results suggest that obstetricians' confidence in vaccination is of outmost importance for implementing immunization in pregnancy and any doubts on vaccine effectiveness and safety should be resolved. Routine antenatal vaccination counseling and pregnancy immunization campaigns are essential to improve vaccine uptake during pregnancy.

Nurturing Infants to Prevent Atopic Dermatitis and Food Allergies: A Longitudinal Study.

BACKGROUND: Atopic dermatitis (AD) at a young age often precedes the development of food allergies. Although AD affects millions of infants worldwide, prenatal and postnatal risk factors, and their association with the development of food allergies later on, are not fully elucidated. This study seeks to investigate AD epidemiology in infancy and its risk factors, examining early-life factors (both prenatal and postnatal) that could contribute to the later development of food allergies. METHODS: Between January 2019 and December 2019, 501 infants were included in this prospective cohort study. Longitudinal data collection was performed through maternal interviews, the first one conducted within three days after the delivery and the second within 24 to 36 months after the delivery, encompassing variables such as demographics, family history of atopy, maternal smoking, antibiotic use during pregnancy, the mode of delivery, breastfeeding history, food practices, and greenness exposure within 3 days from delivery, while they were still in the hospital. RESULTS: Maternal smoking during pregnancy (p = 0.001) and an older sibling atopy history (p = 0.03) was significantly linked to AD incidence. Cesarean section delivery (p = 0.04) was associated with a higher risk of food allergies in infants with AD. Having a garden at home correlated with a higher likelihood of AD (p = 0.01), and food elimination without medical guidance (p = 0.02) due to AD correlated with an elevated risk of food allergies. CONCLUSIONS: Encouraging timely allergenic food introduction while promoting dietary diversity, rich in plant-based foods, maternal smoking cessation, and professional dietary guidance may help minimize AD and food allergy risk. Future studies should address the role of greenness in the development of AD and food allergies.

Hypogonadism in adolescent girls: treatment and long-term effects.

BACKGROUND AND AIM: Hypogonadism in adolescent females presents as delayed puberty or primary amenorrhea. Constitutional delay of growth and puberty, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism represent the principal differential diagnosis of delayed puberty. Girls with hypogonadism require hormone replacement therapy to initiate and sustain puberty. We aimed to provide a brief review concerning treatment for female adolescents with hypogonadism and further to focus on current data regarding long-term effects of therapy. METHODS: The published studies and articles of the international literature were used regarding the approach to adolescent girls with hypogonadism. RESULTS: The aim of therapy is the development of secondary sexual characteristics and achievement of target height, body composition and bone mass, to promote psychosexual health and, finally, to maximize the potential for fertility. Hypogonadal females need long-term HRT, so it is of great importance to fully define risks and benefits of therapy. CONCLUSIONS: The optimal pubertal induction in women contains both estrogens and progesterone regimens.  Different therapeutic options have been described over the years in the literature, but larger randomized trials are required in order to define the ideal approach. The latest acquisitions in the field seem to propose that transdermal 17ß-estradiol and micronized progesterone present the most physiological formulations available for this purpose. Further studies and follow up are needed concerning the long-term effects of HRT in adolescents.

Clinical characteristics and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection in Iran: A multicenter study.

OBJECTIVES: This study aimed to assess the clinical characteristics, treatment and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 in five different geographical regions of Iran. METHODS: In this multicenter observational study, patients <21 years were included between March 2020 and October 2021. By Disease Control and Prevention (CDC) checklist, demographic characteristics, comorbidities, clinical signs and symptoms, laboratory and radiology findings, and treatment were collected. Statistical analysis was using Chi-square and t-test in STATA14. RESULTS: In total 225 patients with median age of 55 (26-96) months were included that 59.56% boys. 57.33% were admitted to the PICU with a median of 7 days (4-10). 95.56% of patients were discharged with recovery and the rest died. All of the patients in our study were included based on the MIS-C criteria. However, some patients had Kawasaki symptoms, so we compared the clinical and epidemiological characteristics of the two groups. Conjunctival injection, cervical lymphadenopathy>1.5 cm diameter, and strawberry tongue in Kawasaki-like MIS-C patients were higher than of MIS-C patients, and this difference was significant(p<0.001). The most common comorbidity was obesity (24.86%). Most patients tested for COVID-19 and about 60% of the patients had a positive test by serology or reverse transcription-polymerase chain reaction (RT-PCR). Gastrointestinal (88.89%) and hematologic signs (84.44%) were most common. Most drugs used in patients were IVIG and steroids. 88.07% and 61.29% of the patients had at least one problem in echocardiography and lung CT, respectively. CONCLUSIONS: The best outcome was seen in patients who were treated with both IVIG and steroids on the first days of admission. Myocarditis was common in two groups of patients. According to most patients had echocardiography abnormal, screening of heart function is recommended for patients.

Pantoea agglomerans Bacteremia: A Rare Case of Bacteremia in an Immunocompetent Four-Year-Old Child.

Pantoea agglomerans is primarily an environmental and agricultural organism that rarely causes disease in healthy individuals. We present a case of P. agglomerans bacteremia in an immunocompetent four-year old boy without comorbidities who presented with fever and increased inflammatory markers. As the exact source of bacteremia could not be established, our case was considered to be an event of primary blood stream infection.

Pericarditis Following Recovery From COVID-19 Infection in a 15-Year-Old Boy: A Postinflammatory Immune-Mediated Presentation or a New-Onset Autoimmune Disease.

As the COVID-19 pandemic evolves, the medical community continues to report a variety of clinical manifestations of SARS-CoV-2 in the pediatric population. Although younger age groups experience less severe disease, attention is given to the immunologic manifestations of the disease. Pericarditis is a rare cardiac complication of COVID-19 infection. We discuss the first case of delayed presentation of pericarditis following recovery from COVID-19 infection in the pediatric population. A 15-year-old male adolescent presented to the emergency department (ED) with a two-day history of left-sided, sub-sternal chest pain that worsened during inspiration and a low-grade fever. Twenty days prior to this presentation, the patient experienced fever and was tested positive for SARS-CoV-2. His family history was remarkable for Hashimoto thyroiditis and rheumatoid arthritis, with his mother having experienced 18 episodes of pericarditis during the exacerbations of her disease. RT-PCR for SARS-CoV-2 was negative on this occasion and the serology assay identified positive IgG antibodies against the virus. The ECG was suggestive for pericarditis and the diagnosis was confirmed by the presence of pericardial effusion on ECHO. The rest of the aetiological investigations for pericarditis were negative. In view of the strong family history of autoimmunity, questions were raised in the medical team of our hospital regarding the etiology of his pericarditis and on whether it represented a postinflammatory immune-mediated presentation of SARS-CoV-2 or a new-onset autoimmune disease.

Miller Fisher Syndrome Triggered by Infections: A Review of the Literature and a Case Report.

AIM: We reported a case of Miller Fisher syndrome following a breakthrough varicella zoster virus infection in an otherwise healthy 6-year-old male. The objective of this review was to summarize the infectious etiologic agents known to trigger Miller Fisher syndrome. METHODS: Review of the literature on infections associated with Miller Fisher syndrome. RESULTS: We identified 762 studies after duplicates were removed. Titles, abstracts, and full texts were screened. Finally, 37 studies were included in qualitative synthesis after citations and reference list were checked. The age range of cases reported was 0-78 years, and male sex was predominant in studies where these parameters were reported. The most common causative agent was Campylobacter jejuni followed by Haemophilus influenzae. CONCLUSIONS: Our review highlights the importance of recognizing the infections triggering Miller Fisher syndrome. We also present a unique case of Miller Fisher syndrome associated with breakthrough varicella zoster virus infection. Preventive policies may consider population immunization for certain causative agents.

Effectiveness of probiotics and synbiotics in reducing duration of acute infectious diarrhea in pediatric patients in developed countries: a systematic review and meta-analysis.

Acute diarrhea is one of the most frequent causes of doctor visits and hospital admissions for children. Our objective was to evaluate the association between probiotics administration and reduction of acute infectious diarrhea duration in children dwelling in developed countries. Bibliographic databases, gray literature, and reference lists were searched up to September 29, 2019. Double-blind, randomized controlled trials that examined probiotics efficacy in children with acute infectious diarrhea residing in developed countries were included. Data were synthesized by generic inverse variance method using fixed- and random-effects model. Twenty trials met the eligibility criteria (n = 3469 patients) and were included in the qualitative synthesis, and 19 studies in meta-analysis. Twelve trials (n = 840) were assessed as high/unclear risk of bias and eight (n = 2629) as low risk of bias. Comparisons revealed a moderate effectiveness of probiotics in low risk of bias studies (MD = - 13.45 h; 95% CI - 24.26, - 2.62; p = 0.02, Bayesian meta-analysis pooled effect MD = - 0.38, 95% CrI - 2.3, 1.58) and a notable effect in studies with high/unclear risk for bias (MD = - 19.70 h; 95% CI - 28.09, - 11.31; p = 0.0004). In trials of optimal methodological quality (n = 1989), probiotics effect was absent (MD = - 3.32 h; 95% CI - 8.78, 2.13, p = 0.23).Conclusion: Outcomes suggest that probiotics do not demonstrate sufficient clinical impact in reducing diarrhea duration in children in the developed countries.Systematic Review Registration: This review is registered at PROSPERO (ID: CRD42020152966). What is Known: • Probiotics, due to the conflicting study results, are administered without adequate evidence as an adjuvant therapeutic agent for eliminating duration of acute infectious diarrhea in pediatric patients. What is New: • In developed countries, probiotics are demonstrated as ineffective in reducing the duration of acute infectious diarrhea in children.

Polymicrobial gastroenteritis in children.

AIM: Co-infections with viral and bacterial enteropathogens often augment severity of diarrhoea, however, there is limited evidence on the clinical importance of bacterial enteric co-infections. We investigated the rate, type and impact of bacterial enteropathogens and their associations in children with gastroenteritis. METHODS: Retrospective cohort study that included children 0-18 years old with acute bacterial diarrhoea during a 27-year period (1993-2019), in Crete, Greece. Differences in clinical characteristics and pathogen associations were investigated between single and multiple infections. RESULTS: Two or more bacteria were isolated in stool culture in 53 out of 1932 children (2.74%). Patients with co-infections were younger (p 0.0001) and had higher hospitalisation rates (p 0.03). Escherichia coli (E. coli) was the most prevalent pathogen associated with co-infections, in particular the E. coli enteropathogenic strains O127 and O111 (p 0.001), and Salmonella spp the least (p 0.001). Co-occurrence analysis revealed two positively associated pathogen pairs, E. coli with Campylobacter spp and E. coli (p 0.001) with Salmonella spp (p 0.04). CONCLUSION: Bacterial enteropathogen co-infection was most common with E. coli strains and related to higher hospitalisation rates and younger age.

Miller Fisher Syndrome Triggered by Infections: A Review of the Literature and a Case Report.

AIM: We reported a case of Miller Fisher syndrome following a breakthrough varicella zoster virus infection in an otherwise healthy 6-year-old male. The objective of this review was to summarize the infectious etiologic agents known to trigger Miller Fisher syndrome. METHODS: Review of the literature on infections associated with Miller Fisher syndrome. RESULTS: We identified 762 studies after duplicates were removed. Titles, abstracts, and full texts were screened. Finally, 37 studies were included in qualitative synthesis after citations and reference list were checked. The age range of cases reported was 0-78 years, and male sex was predominant in studies where these parameters were reported. The most common causative agent was Campylobacter jejuni followed by Haemophilus influenzae. CONCLUSIONS: Our review highlights the importance of recognizing the infections triggering Miller Fisher syndrome. We also present a unique case of Miller Fisher syndrome associated with breakthrough varicella zoster virus infection. Preventive policies may consider population immunization for certain causative agents.

Risk factors for meningococcal disease in children and adolescents: a systematic review and META-analysis.

Invasive meningococcal disease (IMD) remains a major cause of mortality and morbidity in children worldwide. A systemic review in PubMed and Cochrane Controlled Trials Register was performed for articles on risk factors for IMD in children and adolescents published during a 20-year period (19/09/1998 to 19/09/2018). Inclusion and exclusion criteria were established and applied. The data were meta-analyzed using random-effect model and the results were presented on forest plots separately for each risk factor. We identified 12,559 studies (duplicates removed). Titles, abstracts, and full texts were screened and finally, six studies (five case-control and one cohort study) were included in qualitative synthesis, five in meta-analysis. The median age of meningococcal disease (MD) cases was 72.2 months (0-19 years). Household crowding, smoking exposure, close relationships, and recent respiratory tract infections conferred a more than twofold risk for IMD in exposed individuals compared to controls [overcrowded living OR 2.52 (95% CI 1.75-3.63), exposure to smoke OR 2.10 (95% CI 1.00-4.39), kissing OR 2.00 (95% CI: 1.13-3.51), and recent respiratory tract infection OR 3.13 (95% CI 2.02-4.86)]. Attendance of religious events was associated with a decreased risk [0.47 (95% CI, 0.28-0.79)].Conclusion: Our review highlights the importance of individual characteristics as risk factors for IMD in childhood and adolescence. Preventive policies may consider individual as well as social-environmental factors to target individuals at risk.What is Known:• Close relationships, household crowding, and recent respiratory tract infections are major risk factors for IMD.• Passive smoking is a major risk factor for IMD.What is New:• Intimate kissing, household crowding, and passive smoking were found to double the risk of IMD.• Recent respiratory tract infections almost tripled the risk for IMD.

Conjugate vaccines dramatically reshaped the epidemiology of bacterial meningitis in a well-defined child population.

AIM: We explored the impact of vaccination on bacterial meningitis in a well-defined population of children on the island of Crete, Greece, over a 27-y period. METHODS: This was a retrospective observational study of all mandatory notifications of bacterial meningitis in patients aged 1 mo-14 y from 1991 to 2017. RESULTS: There were 245 patients with proven (n = 227) or suspected (n = 18) bacterial meningitis, and eight deaths were recorded, giving a case fatality rate of 3.3%. The mean annual incidence rate (IR) per 100 000 children was 4.9 for Neisseria meningitidis, 2.2 for Streptococcus pneumoniae and 0.4 for Haemophilus influenzae type b (Hib). Cases of meningitis C dropped significantly after the conjugate meningitis C vaccine was licensed for routine vaccination in Greece in 2000 (IR of 1.5 vs 0.3, P < 0.028) while the Streptococcus pneumoniae cases showed a threefold decrease after the PCV13 vaccine was licensed in Greece in 2009 (IR 2.7 vs 1.0, P < 0.03). Vaccination had already eliminated Hib in Greece in the 1990s. CONCLUSION: Bacterial meningitis cases decreased in children following the introduction of the meningitis C and PCV13 vaccines in Greece. Hib had already disappeared and significant reductions in meningitis C and Streptococcus pneumoniae were observed.

Asthma: An Undermined State of Immunodeficiency.

Asthma is a heterogeneous chronic respiratory disease characterized by an increased burden of infections. Respiratory tract infections associated with an increased risk for asthma especially when occurring in the first months of life, also represent the most common cause of asthma exacerbations. The association between asthma and the increased frequency of infections and microbiota dysbiosis might be explained by a common mechanism, such as an underlying immune system defect. Apart from the well-established association between primary immunodeficiencies and asthma, several alterations in the immune response following infection have also been observed in asthmatic patients. An impairment in lung epithelial barrier integrity exists and is associated with both an increased susceptibility to infections and the development of asthma. Asthmatic patients are also found to have a deficient interferon (IFN) response upon infection. Additionally, defects in Toll-like receptor (TLR) signaling are observed in asthma and are correlated with both recurrent infections and asthma development. In this review, we summarize the common pathophysiological background of asthma and infections, highlighting the importance of an underlying immune system defect that predispose individuals to recurrent infections and asthma.

Clinical and immunological features in a cohort of patients with partial DiGeorge syndrome followed at a single center.

DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity, and allergy. The aim of this study was to assess the effect of different factors in the development of infections, autoimmunity, and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low immunoglobulin M levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3+, CD3+CD4+, and naïve CD4+CD45RA+CD27+ T lymphocytes compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T cells, as suggested by an accelerated decline of the naïve T lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4+ T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency.

Susceptibility patterns of uropathogens identified in hospitalized children.

BACKGROUND: Urinary tract infection (UTI) is the most common serious bacterial infection in childhood. The aim of the present study was therefore to identify the organisms responsible for community-acquired febrile UTI in children, to investigate their susceptibility to commonly used antibiotics, and to identify possible risk factors for antibiotic resistance. METHODS: A total of 284 children (male, 38%; female, 62%), who were hospitalized due to a community-acquired UTI over a 5 year period in a general district hospital of southern Greece, were enrolled in the study. RESULTS: Escherichia coli was the leading uropathogen followed by Klebsiella spp. (9.15%) and Proteus spp. (5.28%). E. coli isolates were most commonly resistant to ampicillin (41.8%), followed by piperacillin (40.3%), amoxicillin-clavulanic acid (28.6%) and trimethoprim-sulfamethoxazole (17.8%), while 27 strains (12.6%) were multi-drug resistant (MDR). Of the E. coli strains, 4.21% were producing extended-spectrum beta-lactamases. Parenteral second- and third-generation cephalosporins, the most commonly used antibiotic agents (81.3%) in the present cohort, remained highly active against E. coli and other urinary isolates, given that >95% of E. coli strains were susceptible to cefuroxime and cefotaxime. Vesicoureteral reflux was a significant risk factor for MDR (P = 0.04). CONCLUSION: Contrary to current local practice, amoxicillin/clavulanic acid may not be the best option for the empirical treatment of community-acquired UTI in southern Greece.

Interpretation of lymphocyte subset counts by the general pediatrician.

The immune system poses one of the greatest challenges for the scientific community. The general pediatrician should be able to screen and identify an immunodeficient patient based on certain clinical indications. Further investigation is crucial for the distinction between primary or secondary immunodeficiency as well as for between cellular and humoral immunity defects. Full blood count is the best initial laboratory test when suspecting a primary immunodeficiency, focusing on the absolute lymphocyte count, while lymphocyte subset count offers the advantage of detecting the cell type that causes the immune defect. The aim of the present review was to guide the general pediatrician in the investigation and diagnosis of an immunodeficient patient. Even though an immunodeficiency may seem a very difficult disease to diagnose, a balanced and rational way of thinking, along with the help of modern technological advances, can easily guide us in the right direction.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis.

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor-negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely.

Gastrointestinal manifestations of primary immune deficiencies in children.

Primary immune deficiencies (PID) in children are a rare but serious group of genetic disorders of the immune system which apart from the host's defenses, can also affect every system of the human body, including the gastrointestinal tract. In their severe form they can lead to increased susceptibility to serious infections during infancy and even death. In the less severe form, they can present later in childhood or adolescence with subtle signs and symptoms. As PID can often mimic gastrointestinal diseases, children presenting with atypical gastrointestinal disease and/or failure to respond to conventional therapy should be evaluated for an underlying primary immune disorder and initiated appropriate treatment. The current review of the literature will summarize the gastrointestinal manifestations of primary immune deficiencies in children.

Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab.

Rituximab (RTX) is a monoclonal antibody against CD20, commonly used in the treatment of hematological malignancies and autoimmune diseases. The use of RTX is related to the development of hypogammaglobulinemia and infections. Aim of this review is to summarize the evidence supporting the association of specific risk factors with the development of hypogammaglobulinemia and infections post-RTX. Immunological complications are more common in patients with malignant diseases as compared to non-malignant diseases. Moreover, the use of more than one dose of RTX, maintenance regimens, low pre-treatment basal immunoglobulin levels and the association with Mycophenolate and purine analogues represent risk factors for the development of hypogammaglobulinemia. The number of RTX courses, the evidence of low IgG levels for more than 6 months, the use of G-CSF, the occurrence of chronic lung disease, cardiac insufficiency, extra-articular involvement in patients with rheumatoid arthritis, low levels of IgG and older age have been correlated with a higher risk of infections. Even though the heterogeneity of the studies in terms of study population age and underlying disease, RTX schedules as well as differences in pre-treatment or concomitant therapy doesn't allow drawing definitive conclusions, the study of the literature highlight the association of specific risk factors with the occurrence of hypogammaglobulinemia and/or infections. A long term randomized controlled clinical trial could be useful to define a personalized evidence-based risk management plan for patients treated with RTX.