Food allergy: cause or consequence of pediatric eosinophilic esophagitis? Potential implications of ultraprocessed foods in prevention and management

: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by eosinophilic infiltration, leading to esophageal dysfunction, inflammation, and fibrotic remodeling. In the last few decades, there has been an increased prevalence of EoE at an alarming rate in the pediatric age. The pathogenesis of EoE is still largely undefined, and this limits the definition of effective strategies for the prevention and management of this condition. EoE is considered a multifactorial disease arising from a negative interaction between environmental factors and genetic background, causing an impaired esophageal epithelial barrier with subsequent abnormal allergen exposure activating type 2 (Th2) inflammation. Food antigens have been suggested as key players in Th2 inflammation in pediatric patients with EoE, but emerging evidence suggests a potential role of other dietary factors, including ultraprocessed foods, as possible triggers for the occurrence of EoE. In this paper, we discuss the potential role of these dietary factors in the development of the disease, and we propose a new approach for the management of pediatric patients with EoE

An asymptomatic mediastinal cyst in a young child: Case report and summary of the literature

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Clinical and immunological phenotypes of selective IgM deficiency in children: Results from a multicenter study

background: a few studies assessed the clinical and immunological features of selective IgM deficiency (SIgMD), especially in the pediatric age. we aimed to characterize the clinical and immunological phenotypes of a cohort of pediatric patients with SIgMD according to the different diagnostic criteria available. methods: In this multicenter study, we evaluated pediatric SIgMD patients diagnosed at the pediatric clinic in pavia, Italy, or through the Italian primary Immunodeficiency NETwork (IPINET) and monitored changes in their diagnosis over a time frame that ranges from several months to several years. results: forty-eight patients with SIgMD were included (mean serum IgM: 33 mg/dL). the most common clinical manifestations were recurrent infections (67%) and allergies (48%). subgroup analysis according to SIgMD definition criteria of the european society for Immunodeficiencies (ESID) showed no significant difference in clinical manifestations, also considering the group with additional immunological abnormalities. sixteen patients had long-term follow-up, during which 87% preserved their SIgMD diagnosis, while two patients showed a reduction in IgA in addition to low IgM. conclusions: our data suggest that the identification of a reduction in serum IgM in children should lead to a complete immunological work-up to obtain a comprehensive clinical and immunological characterization of the patient. the follow-up of these patients is fundamental to define the disease evolution and appropriate management

Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

: Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy

Implementing Precision Medicine in Pediatric Eosinophilic Gastrointestinal Disorders

Eosinophilic gastrointestinal diseases (EGIDs), particularly eosinophilic esophagitis (EoE), are emerging, heterogeneous, and chronic disorders affecting adults and children equally. Although several efforts have been made in the last decade, many unmet needs remain unsolved. We investigated some of these aspects, achieving several notable findings. We find that the epidemiology of non-EoE EGIDs in symptomatic patients is higher than that reported in observational studies or surveys, highlighting that these disorders are common and should be included in the differential diagnostic process of inflammatory gastrointestinal diseases. We collected data on patients with EGIDs followed at our Pediatric Hospital for five years, and we found that 1) the epidemiology of these conditions is increased; thus, EGIDs are not rare diseases; 2) EGIDs affect patients with atopic comorbidities and children with non-atopic diseases, suggesting different potential phenotypes; 3) symptoms are unspecific and depend on the site of intestinal inflammation. Subsequently, we first identified three potential phenotypes of pediatric EGIDs using a cluster analysis approach. Notably, we confirmed and characterized two subgroups of EoE patients, an atopic and non-atopic phenotype, with a relevant impact on clinical practice and potential significance in prognosis and response to therapy. The clinical heterogeneity of EGIDs and the absence of specific noninvasive biomarkers are probably the main limitations to a prompt diagnosis and a shorter diagnostic process, especially in non-esophageal EGID cases. We identified that the diagnostic time is significantly associated with impaired child growth in children with EGIDs, highlighting that raising awareness among family pediatricians on EGIDs and promptly referring suspicious cases to specialized pediatric centers is fundamental. On the other hand, allergists and gastroenterologists should promptly consider GI endoscopy in all those children with refractory GI symptoms, especially if complicated by atopy, peripheral eosinophilia, failure to thrive, or feeding issues. EoE significantly impacts the quality of life of affected children, primarily because of the absence of noninvasive biomarkers and the need to periodically monitor treatment response with esophagogastroduodenoscopy. Consequently, identifying noninvasive biomarkers is an urgent need in pediatric EoE management. The last part of Ph.D. research aimed to identify potential noninvasive biomarkers for EoE diagnosis and monitoring, assessing disease activity with the new proposed set of outcome measures for improving the data quality of trials and observational studies (COREOS). We identified three promising noninvasive biomarkers for EoE diagnosis and surveillance using a panel of inflammatory, tissue, vascular, and eosinophil-derived markers. We found that interleukin (IL)-17 values predicted clinically, endoscopically, and histologically active disease. As reported in the asthma model, high expression of IL-17 might define a potential “Th-2 low" endotype, which might correspond to a severe and difficult-to-treat EoE phenotype. In the case-control comparison, galectin (GAL)-10 and transforming growth factor (TGF)-β values were significantly increased in EoE patients compared to healthy, non-allergic children. The results of this explorative prospective study are promising and open new scenarios in EoE diagnosis and surveillance that should be investigated with further and more extensive studies

Malnutrition in Eosinophilic Gastrointestinal Disorders

Primary eosinophilic gastrointestinal disorders (EGIDs) are emerging chronic/remittent inflammatory diseases of unknown etiology, which may involve any part of the gastrointestinal (GI) tract, in the absence of secondary causes of GI eosinophilia. Eosinophilic esophagitis is the prototype of eosinophilic gastrointestinal disorders and is clinically characterized by symptoms related to esophageal inflammation and dysfunction. A few studies have assessed the nutritional status of patients with eosinophilic gastrointestinal disorders, showing conflicting results. This review summarizes the current evidence on the nutritional status of patients with EGIDs, focusing on the pediatric point of view and also speculating potential etiological mechanisms

COVID-19 and allergy: How to take care of allergic patients during a pandemic?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is a new strain of coronavirus that has not been previously identified in humans. SARS-CoV-2 is recognized as a highly contagious respiratory virus with severe morbidity and mortality, especially in vulnerable populations. Being a novel disease, everyone is susceptible, there are no vaccine and no treatment. To contain the spread of the disease, health authorities throughout the world have restricted the social interactions of individuals in various degrees. Allergists, like other physicians, are faced with the challenge of providing care for their patients, while protecting themselves and patients from getting infected, with strategies that are in continuous evolution as states work through the different stages of social distance. Allergist provides care for patients with the most common non-communicable disease in the world: asthma, allergic rhinitis, food allergy, venom allergy, drug allergy atopic dermatitis, and urticarial syndromes. Some of these diseases are not only considered risk factors for severe reactions but also have symptoms such as cough and sneezing that are in differential diagnosis with COVID-19. As we move forward, allergy symptoms may prevent patients from working, go to school, or access medical services that increasingly are allowing only asymptomatic individuals. In this review, we will outline how to take care safety of different allergic patients during the pandemic

How pediatric resident's life has changed during the COVID-19 pandemic

Since the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a global pandemic, a few articles were published on the working experience of pediatric residents, especially from the most exposed countries worldwide. Pediatric residents continue to be essential pillars in managing and treating pediatric diseases and are currently fundamental health care providers for every ill patient, including children and adolescents with COVID-19. Although severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is changing everyone's life, this previously unknown disease can represent a training tool and a hard challenge for pediatric residents to improve their skills and take part in an ongoing process of knowledge

The relevance of symptom perception in the management of severe asthma in adolescents

Severe asthma in adolescents is a demanding challenge that deserves adequate management, including thorough work-up and rigorous follow-up

COVID-19 and autoimmune diseases: is there a connection?

Purpose of reviewThis review summarizes current evidence on the potential link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and autoimmunity.Recent findingsSeveral viral infections are potential triggers of reactive and autoimmune diseases by inducing type II and type IV hypersensitivity reactions. Recent evidence demonstrated that SARS-CoV-2 infection is not an exception, triggering the production of tissue-specific autoantibodies during the acute phase of coronavirus disease 2019 (COVID-19) and leading to autoimmune diseases development as long-term complication. The significant immune dysregulation with cytokine storm and organ damage observed in patients with severe to critical COVID-19 is considered the main mechanism explaining the high levels of autoantibodies, which are also implicated in disease severity and the need for an intensive care assessment. Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated disease where the recent viral infection leads to systemic inflammation, as already observed in other reactive and autoimmune diseases.Autoimmunity may be a complication of SAR-CoV-2 infection. Understanding the pathogenesis of autoimmune manifestations in COVID-19 might help prevent the incidence or exacerbation of autoimmune disorders and design better and more efficient treatment strategies in children and adult populations