Vernal keratoconjunctivitis and eosinophilic esophagitis: A rare combination?

Vernal keratoconjunctivitis (VKC) is a bilateral ocular inflammatory disease with a conjunctival and corneal involvement and typical onset during childhood. Eosinophilic esophagitis (EoE) is a chronic disease characterized by eosinophilic inflammation of the mucosa (≥15 eosinophils/HPF) and symptoms of esophageal dysfunction. EoE and VKC are both immune-mediated diseases sharing a similar pathogenetic mechanism and a high association with other allergic diseases. Nevertheless, no data are currently available about their clinical association. We present 4 cases of concomitant diagnosis of vernal keratoconjunctivitis and eosinophil esophagitis suggesting that these conditions may coexist in the same patient more frequently than expected. Health care providers should be aware of the possibility of co-occurrence in their daily practice.

A possible unexpected link: Could wheat elimination trigger food protein-induced enterocolitis syndrome in a celiac disease patient?

Cases of association between celiac disease and wheat allergy have been described in the literature. However, to date, no reported cases have linked celiac disease with wheat food protein-induced enterocolitis syndrome (FPIES). We report a case of this association. A child diagnosed with celiac disease at the age of 2 years, following a gluten-free diet, experienced uncontrollable vomiting, and subsequent hypotension within 2 h of accidental ingestion of wheat flour. As a result, the child required hospitalization for fluid therapy. A similar episode occurred when the child turned 5 y, again resulting from accidental gluten ingestion. This time, the symptoms included vomiting, hypotension, and a loss of consciousness, leading to hospitalization for rehydration treatment. After this second episode, on suspicion of FPIES, the patient was referred to the pediatric allergists, who confirmed the diagnosis. To our knowledge, this is the first case of an association between celiac disease and FPIES. It has been hypothesized that exclusion diets in food-allergic children may lead to an increase in specific immunoglobulin E levels for those foods and, consequently, the risk of anaphylaxis. However, FPIES is not an immunoglobulin E-mediated condition. Hence, further investigations are warranted to elucidate the underlying mechanisms linking these 2 disorders.

Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults.

BACKGROUND: Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. RESEARCH QUESTION: How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? STUDY DESIGN AND METHODS: This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1 month, 3 months, and 6 months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. RESULTS: Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV1 increased initially and then remained stable. BMI also increased significantly from T0 to 6 months (P < .01). Depression improved from T0 to 1 month (P < .001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10% to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). INTERPRETATION: This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator.

Heterogeneity of weight gain after initiation of Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis.

BACKGROUND: The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy. METHODS: We conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment's effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term. RESULTS: The mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3-6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively. CONCLUSIONS: Our results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications.

Endotypes of Nasal Polyps in Children: A Multidisciplinary Approach.

Nasal polyps (NPs) are rarely reported in childhood and usually represent red flags for systemic diseases, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and immunodeficiencies. The European Position Paper released in 2020 (EPOS 2020) provided a detailed classification and defined the correct diagnostic and therapeutic approaches. We report a one-year experience of a multidisciplinary team, made up of otorhinolaryngologists, allergists, pediatricians, pneumologists and geneticists, with the aim of ensuring a personalized diagnostic and therapeutic management of the pathology. In 16 months of activity, 53 patients were admitted (25 children with chronic rhinosinusitis with polyposis and 28 with antro-choanal polyp). All patients underwent phenotypic and endo-typic assessment, using proper classification tools for nasal pathology (both endoscopic and radiological), as well as adequate cytological definition. An immuno-allergic evaluation was carried out. Pneumologists evaluated any lower airway respiratory disease. Genetic investigations concluded the diagnostic investigation. Our experience enhanced the complexity of children's NPs. A multidisciplinary assessment is mandatory for a targeted diagnostic and therapeutic pathway.

Vernal keratoconjunctivitis in Down syndrome: a case report.

BACKGROUND: Down syndrome (DS) or Trisomy 21 is the most common chromosomal disease and is characterized by possible heart defects, cognitive impairment and visual disorders. CASE PRESENTATION: We describe for the first time a 17-year-old Caucasian girl suffering from Down syndrome associated with vernal keratoconjunctivitis (VKC), a rare disorder of the anterior segment of the eye, characterized by intense photophobia, redness, watering eyes and itching due to an inflammatory-allergic reaction of the cornea and conjunctiva. On slit-lamp examination, the girl showed conjunctival hyperemia, papillary hypertrophy, giant papillae and corneal leukoma in right eye as a result of a previous corneal ulcer. A successful topical immunosuppressant therapy with cyclosporin 1% was started. CONCLUSION: So far, to our knowledge, this is the first description of VKC in a patient with DS. Finding an inflammatory-allergic disease such as VKC in DS is unusual but it must be taken into account because keratoconus, one of the most frequent eye pathologies in DS, can be secondary to an unrecognized VKC.

An inflammatory Signature of Glucose Impairment in Cystic Fibrosis.

Objective and Design: Cystic fibrosis-related diabetes (CFRD) is a severe complication associated with increased morbidity and mortality in cystic fibrosis (CF) patients. Extensive inflammatory state in CF leads to pancreas damage and insulin resistance with consequent altered glucose tolerance and CFRD development. The aim of the present study was to identify circulating levels of inflammatory markers specifically associated with impaired glucose tolerance (IGT) and overt CFRD in a sample of young adults with CF. Materials and Methods: Sixty-four CF outpatients, without evident active pulmonary exacerbation, infectious and autoimmune diseases, were enrolled in the study and the levels of 45 inflammatory serum mediators were measured through x magnetic bead panel multiplex technology. Results: Serum levels of PDGF-AA, CCL20/MIP3α, IFNα, CCL11/eotaxin, CXCL1/GROα, GMCSF, B7H1/PDL1, IL13, IL7, VEGF, and TGFα were all significantly (p<0.05) elevated in patients according to glycemic status and directly correlated with glycated hemoglobin and C-reactive protein levels. Conclusion: Our findings suggest that increased levels of specific circulating inflammatory mediators are directly associated with impaired glucose tolerance in CF patients, thus, potentially implicating them in CFRD pathogenesis and warranting larger longitudinal studies to validate their monitoring as predictor of CFRD onset.

The effect of COVID-19 imposed lockdown on Italian children with Vernal Keratoconjunctivitis.

Background: Vernal keratoconjunctivitis (VKC) is a chronic, inflammatory-allergic disease of the cornea and conjunctiva. Environmental factors, such as light exposure, have been supposed to play a role in the pathogenesis of ocular inflammation and in the worsening of VKC. Objective: The aim of this study was to estimate the impact of reduced sunlight exposure in patients with VKC during the imposed lockdown period for the SARS-CoV-2 pandemic emergency. Methods: We retrospectively reviewed data of patients with VKC visited during spring season in 2020 and 2019 at Vernal Keratoconjunctivitis Multidisciplinar Outpatient of our Hospital.Subjective symptoms were evaluated by Visual analogue scale (VAS) and VKC severity was graded by Bonini scale. Quality of life was evaluated by Correlations of Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire. The number of hours of e-learning as well as of hours spent in front of a bright screen (PC, TV, mobile, tablet play station, and so on) was also investigated. Results: Twenty-nine male subjects (mean ± SD age: 8.74 ± 2.40 years) with VKC were included in the study. Most of the patients (17/29) were sensitized individuals.No significant changes in Bonini severity score and in VAS evaluation were observed comparing 2020 to 2019 values. Ten (34.4%) patients did benefit from the reduced sunlight exposure. The increased use of bright screens was associated with worsening of VKC severity. Conclusions: Sunlight exposure plays a role in VKC exacerbation in about one third of patients. The number of hours spent in front of bright screens may influence severity of VKC symptoms.

Developing National and International Guidelines.

Food allergy (FA) is considered an emerging public health problem. The development of evidence-based guidelines aims to help health care professionals in an accurate diagnosis and management of such diseases. It is proven that there are differences in the factors that determine FA in the different regions of the world. It is necessary to encourage standardization processes of guidelines development. Nevertheless, in the future it will be necessary to take into consideration not only a methodologically correct analysis of the evidence but also the socio-economic realities where the guidelines will be applied.

Health-related quality of life in children at the diagnosis of Vernal Keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, allergic condition mostly affecting children. Clinical evaluations may not necessarily reflect the impact of the disease on the patients' health-related quality of life (HRQoL). We aimed to evaluate HRQoL in children at VKC diagnosis and to analyze correlations between HRQoL and clinical and laboratory variables. METHODS: We studied 5- to 12-year-old patients with VKC. Data on clinical history, instrumental eye evaluations, blood examinations, and visual analog scale (VAS) for the subjective symptoms were collected. HRQoL was assessed through a disease-specific validated Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire. RESULTS: Seventy subjects were included in the analysis (female/male: 10/60; tarsal/mixed VKC form: 36/34). Clinical severity of VKC according to the Bonini scale was as follows: 14, mild; 36, moderate; and 20, severe. No significant difference was found concerning the distribution of patient age, gender, and history of allergic manifestations between tarsal and mixed VKC. A significant positive correlation was found between all QUICK scores and VAS scores, including different VAS subscale, while no significant correlation was found between QUICK scores and total sign scores, Schirmer's test, and corneal thickness. The presence of active severe VKC was not associated with worse HRQoL. CONCLUSIONS: Our evidence shows that VKC patients experience impairment of HRQoL, especially in relation to the perception of symptoms independently of the ophthalmologic changes found, and that the QUICK questionnaire could be a useful tool to evaluate HRQoL in children with VKC, which may improve patients' classification and management.

Probiotics in food allergy.

PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the possible role of probiotics for food allergy (FA). RECENT FINDINGS: Animal model and in vitro evidence suggest that the gut microbiome could protect against FA and that probiotics could be a valid instrument. There is no consistent evidence in identifying the specific species, the dosage, and the optimal duration to obtain the correct immunomodulation. Early life supplementation with specific 'missing' immunomodulatory microbes - derived from machine learning approach to birth cohort studies - might represent a novel approach to the primary prevention of multiple human atopic diseases. However, further studies are needed. SUMMARY: Currently, there is no positive recommendation from the main scientific societies to use probiotics neither for the treatment nor for the prevention of FA.

Gut Microbiota Profile in Children with IgE-Mediated Cow's Milk Allergy and Cow's Milk Sensitization and Probiotic Intestinal Persistence Evaluation.

Food allergy (FA) and, in particular, IgE-mediated cow's milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow's milk allergic (CMA) infants with that of cow's milk sensitized (CMS) infants and Healthy controls. The effect of the intake of a mixture of Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 on gut microbiota modulation of CMA infants and probiotic persistence was also investigated. Gut microbiota of CMA infants resulted to be characterized by a dysbiotic status with a prevalence of some bacteria as Haemophilus, Klebsiella, Prevotella, Actinobacillus and Streptococcus. Among the three strains administered, B.longum subsp. infantis colonized the gastrointestinal tract and persisted in the gut microbiota of infants with CMA for 60 days. This colonization was associated with perturbations of the gut microbiota, specifically with the increase of Akkermansia and Ruminococcus. Multi-strain probiotic formulations can be studied for their persistence in the intestine by monitoring specific bacterial probes persistence and exploiting microbiota profiling modulation before the evaluation of their therapeutic effects.

Allergy prevention through breastfeeding.

PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the role of breastfeeding as primary prevention tool for allergic diseases. RECENT FINDINGS: Human milk contains vast amounts of biologically active components that have a significant impact on the development of the gut microbiota. Exclusively breastfed infants show a different microbiota, with a predominance of Bifidobacterium species in their intestines.The mechanisms underlying the antiallergic effects of human milk are most probably complex, as human milk contains not only nutritional substances but also functional molecules including polysaccharides, cytokines, proteins, and other components which can produce an epigenetic modulation of the innate and adaptive immune responses of the infant in very early life. SUMMARY: Currently, there is not sufficient strong evidence to guarantee its effectiveness in allergy prevention and therefore the main international scientific societies still do not count it among the recognized primary prevention strategies of allergy.

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry.

BACKGROUND: Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. METHODS: Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. RESULTS: 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). CONCLUSIONS: The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.

Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol.

Food protein-induced allergic proctocolitis (FPIAP) is a condition characterized by inflammatory changes in the distal colon in response to one or more foreign food proteins because of immune-mediated reactions. FPIAP prevalence estimates range widely from 0.16% in healthy children and 64% in patients with blood in stools. In clinical practice, FPIAP is diagnosed when patients respond positively to the elimination of a suspected triggering food allergen. Nevertheless, significant proportions of infants get misdiagnosed with IgE mediated allergy and undergo unnecessary dietary changes. Diagnosis is based on clinical symptoms, a good response to an allergen-free diet and the recurrence of symptoms during the "allergy challenge test". Sometimes clinical features may be non-specific and the etiology of rectal bleeding in childhood may be heterogeneous. Therefore, it is crucial to exclude a variety of other possible causes of rectal bleeding in the pediatric age group, including infection, anal fissure, intestinal intussusception and, in infants, necrotizing enterocolitis and very early onset inflammatory bowel disease. The diagnostic workup includes in those cases invasive procedures such as sigmoidoscopy and colonoscopy with biopsies. The high prevalence of FPIAP contrasts with the lack of known information about the pathogenesis of this condition. For this reason and due to the absence of a review of the evidence, a literature review appears necessary to clarify some aspects of allergic colitis. The aim of the review is to fill this gap and to lay the foundations for a subsequent evidence-based approach to the condition.

Perusal of food allergens analysis by mass spectrometry-based proteomics.

Food allergy is the disease where the immune system is elicited by antigens in food. Although innocuous for immune-tolerant individuals, an ever-growing number of food allergenic people are being registered worldwide. To date, no treatment to cure food allergy is available and the disease management relies on the careful exclusion of the allergenic food from the diet of the allergic individuals. Great efforts are ongoing to clarify the allergenic mechanisms of the diverse allergenic proteins of food origin, aimed to both designing suitable therapies and for a timely and precise diagnosis of the allergic condition. Among the other omics sciences, mass spectrometry (MS)-based proteomics is gaining a steadily increasing interest by the whole scientific community acknowledged its high versatility. In the present work, the latest proteomics based-studies on allergenic proteins are reviewed to provide guidance on the different MS-based methodologies adopted in the research on food allergens. Our review points to highlight the strengths of the MS-based proteomics and how these have been exploited to address specific research questions. Also, the most common drawbacks encountered in a proteomic study are discussed, providing an overview that helps novel researchers in choosing the more suitable experimental workflow. SIGNIFICANCE: Wide wealth of knowledge arising from the various MS-based proteomic investigations is improving our understanding of food allergy through molecular characterization of food allergens. The present work reviews the key aspects to be evaluated while investigating food allergens by means of MS-based proteomics and provide guidance to the novel research groups approaching to the fascinating world of MS-based food allergens detection.

Allergy No more fear of needles!

Needleless injection systems are nowadays widespread and are mainly used to overcome the common problems of needle injection systems, such as pain, hematoma, scar tissue formation, infection or abscess, possibility of accidentally injecting into a venous vessel, and transmission of infectious diseases. All these problems are independent of the type of drug injected and are exclusively related to the needle devices. Current needleless injection systems are a valuable tool, which is especially available for the administration of vaccines to large numbers of patients. Our experience focused in particular on the so-called "jet injectors," of which one of the most valid representatives is Injex®. Our patent essentially concerns a medical needleless device, suitable to inject a subcutaneous AIT (allergy immunotherapy). The mechanism at the base of our device works with compressed air by means of a spring: It is very simple and similar to that of compressed air guns. Once the syringe has been filled, it is placed perpendicular to the skin, and then, the device is activated. The pressure vaporizes the drug, without changing or altering its chemical structure; it makes it pass through the epidermis, until it quickly reaches the subcutaneous layer, at a depth between 3.2 and 9.1 mm, without the patient feeling any pain. The entrance hole made by the needleless device in the epidermis is 0.17 mm rather than 0.39 mm of a normal needle. This type of administration also allows a uniform and spray diffusion of the drug, without causing localized inflammation, as it sometimes happens with normal syringe.

Consensus communication strategies to improve doctor-patient relationship in paediatric severe asthma.

BACKGROUND: Asthma is a chronic inflammatory disease that is very common among youth worldwide. The burden of this illness is very high not only considering financial costs but also on emotional and social functioning. Guidelines and many researches recommend to develop a good communication between physicians and children/caregiver and their parents. Nevertheless, a previous Italian project showed some criticalities in paediatric severe asthma management. The consensus gathered together experts in paediatric asthma management, experts in narrative medicine and patient associations with the aim of identify simple recommendation to improve communication strategies. METHODS: Participants to the consensus received the results of the project and a selection of narratives two weeks before the meeting. The meeting was structured in plenary session and in three working groups discussing respectively about communication strategies with children, adolescents and parents. The task of each working group was to identify the most effective (DO) and least effective practices (DON' T) for 5 phases of the visit: welcome, comprehension of the context, emotions management, duration and end of the visit and endurance of the relationship. RESULTS: Participants agreed that good relationships translate into positive outcomes and reached consensus on communication strategies to implement in the different phase of relationships. CONCLUSIONS: The future challenges identified by the participants are the dissemination of this Consensus document and the implementation of effective communication strategies to improve the management of pediatric asthma.