Evaluation of treatment and long-term management of anaphylaxis in pediatric departments of Greece: a 2-year nationwide survey.

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.

Drug allergy evaluation in children with suspected mild antibiotic allergy.

Background: Adverse antibiotic reactions caused by an immunological mechanism are known as allergic reactions. The percentage of reported antibiotic allergies is likely to differ from the one validated after a drug provocation test (DPT) with the culprit antibiotic. This study aimed to compare the percentage of children who were thought to be allergic to a certain antibiotic with those who have a true allergy, as confirmed by DPTs. We also validated Skin Prick Tests (SPTs) and Intradermal Tests (IDTs) by assessing their sensitivity and specificity, in diagnosing antibiotic allergies using DPT as the gold standard. Furthermore, we investigated epidemiological risk factors such as personal and family history of atopic disease and eosinophilia. Methods: Children with a history of possible allergic reaction to an antibiotic underwent a diagnostic procedure that included: (1) Eosinophil blood count, (2) SPTs, (3) IDTs and (4) DPTs. The parameters were compared with Pearson's Chi-Square and Fisher's Exact Test. Several risk factors that were found significant in univariate analysis, such as personal and family history of atopic disease, and positive SPTs and IDTs were examined with multiple logistic regression analysis to see if they were related to a higher risk for a positive DPT. Results: Semi-synthetic penicillin was the most common group of antibiotics thought to cause allergic reactions in this study. Overall, 123 children with a personal history of an adverse reaction to a certain antibiotic, were evaluated. In 87.8% of the cases, the symptoms had occurred several hours after administration of the culprit antibiotic. Both SPTs and IDTs had low sensitivity but high specificity. Moreover, they had a high positive predictive value (PPV). In contrast, eosinophilia was not recognized as a risk factor. Seventeen patients (13.8%) had a true antibiotic allergy, as confirmed by a positive DPT. A positive IDT was a strong predictor of a positive DPT, along with a positive personal and family history of atopy. Conclusion: SPTs and IDTs are very reliable in confirming antibiotic allergy when found positive. A negative result of a SPT highly predicts a negative DPT. A positive IDT and a positive personal and family history of atopy were recognized as significant risk factors for antibiotic allergy.

Management of antibiotic allergy in children: a practical approach.

BACKGROUND: About 10% of children are declared as allergic to antibiotics, with beta(ß)-lactams being the most common perpetrators. However, few of these are confirmed by allergy tests. This characteristic of being allergic follows a child well into adulthood, leading to alternative, usually more expensive broad-spectrum antibiotics, contributing to antibiotic resistance and increasing healthcare expenses. OBJECTIVE: This review presents a practical approach to managing pediatric patients with antibiotic hypersensitivity reactions. MATERIAL AND METHODS: We updated the guidelines on antibiotic allergy in children by conducting systematic literature research using the best available evidence from PubMed search by entering the keywords "antibiotic allergy" and "children." The search output yielded 5165 citations. RESULTS: Management of antibiotic allergy depends on the culprit antibiotic, and it includes confirmation of the diagnosis and finding a safe alternative to the culprit antibiotic. In particular patients with a history indicative of penicillin allergy can be treated with cephalosporins as an alternative to penicillin, especially with third-generation cephalosporins, except for those with similar R1 side chains. In patients with a history of immediate-type reactions to cephalosporins who require treatment with cephalosporins or penicillin, skin tests with cephalosporin or penicillin with different side chains should be performed. If allergy to macrolides is suspected, challenge tests are currently the only reliable diagnostic tool. The best strategy for managing patients with sulfonamide hypersensitivity is an alternative antibiotic. The skin prick tests and intradermal tests are not recommended for diagnosis of quinolone allergy, as they can activate dermal mast cells leading to false-positive results. Quinolone challenge test is the most appropriate test for diagnosing quinolone hypersensitivity. CONCLUSION: Although adverse drug reactions to antibiotics are frequently documented, immunologically mediated hypersensitivity is unusual. In the event of an reaction, an appropriate diagnostic workup is required to identify the drug's causal role. It is critical to avoid "labeling" a child as allergic without first conducting a proper diagnostic workup.

Management of antibiotic allergy in children: a practical approach

Background: About 10% of children are declared as allergic to antibiotics, with beta(β)-lactams being the most common perpetrators. However, few of these are confirmed by allergy tests. This characteristic of being allergic follows a child well into adulthood, leading to alternative, usually more expensive broad-spectrum antibiotics, contributing to antibiotic resistance and increasing healthcare expenses.Objective: This review presents a practical approach to managing pediatric patients with antibiotic hypersensitivity reactions.Material and methods: We updated the guidelines on antibiotic allergy in children by conducting systematic literature research using the best available evidence from PubMed search by entering the keywords “antibiotic allergy” and “children.” The search output yielded 5165 citations.Results: Management of antibiotic allergy depends on the culprit antibiotic, and it includes confirmation of the diagnosis and finding a safe alternative to the culprit antibiotic. In particular patients with a history indicative of penicillin allergy can be treated with cephalosporins as an alternative to penicillin, especially with third-generation cephalosporins, except for those with similar R1 side chains. In patients with a history of immediate-type reactions to cephalosporins who require treatment with cephalosporins or penicillin, skin tests with cephalosporin or penicillin with different side chains should be performed. If allergy to macrolides is suspected, challenge tests are currently the only reliable diagnostic tool. The best strategy for managing patients with sulfonamide hypersensitivity is an alternative antibiotic. The skin prick tests and intradermal tests are not recommended for diagnosis of quinolone allergy, as they can activate dermal mast cells leading to false-positive results. Quinolone challenge test is the most appropriate test for diagnosing quinolone hypersensitivity (AU)

COVID-19 mRNA Vaccination Mimicking Heart Attack in a Healthy 56-Year-Old Physician.

We report our experience regarding a 56-year-old physician who developed severe symptoms mimicking a heart attack a few days after receiving the second dose of the new mRNA vaccine of Pfizer-BioNTech for COVID-19 protection. The patient is a healthy individual with no comorbidities and a normal clinical and laboratory profile. Five days after receiving the second dose on his left shoulder, he manifested sudden, severe pain on the whole left arm which lasted for about one hour, gradually intensifying and migrating to the chest and presenting as severe angina or heart attack. All work-up, however, was negative, with no evidence of ischemic heart attack or myocarditis. Severe acute symptoms lasted for about 20 h and completely resolved after 36 h. Although myocarditis as a potential side effect of the vaccine with associated heart pain has been identified, chest pain mimicking heart attack with otherwise normal workup has not been reported. Physicians must consider this likely rare and self-resolving symptom in order to increase awareness and prevent themselves and their patients from increased anxiety and unnecessary laboratory investigations.

De novo HBV Hepatitis in a Child with Liver Transplantation.

Background: Omental torsion (OT) presents as a rare, infrequent pathology with often non-specific symptoms. This condition occurs when the greater omentum is twisted around its axis, producing perfusion defects and vascular impairment of the organ. This case report describes an overweight 26-year-old Caucasian man presenting with acute abdomen in previous appendectomy, whose definitive surgical diagnosis was omental torsion. Omental torsion is a rare pathology regarding the causes of acute abdomen associated with a challenging diagnosis. Case report: We report about a female toddler with liver transplantation due to extrahepatic biliary atresia, who was detected to have positive HBsAg, 27 months after transplantation. Before liver transplantation, routine serologic assessments were negative for HBV infection, the child was vaccinated with three doses of HBV vaccine and developed seroprotective Abs titers. Organ donor was the father, who was negative for HBV infection had negative anti-HBc and had seroprotective titers of anti HBs. A PCR assay in our patient revealed the presence of serum HBV DNA with an increased viral load. The patient started antiviral treatment with Entecavir and had serological response within three months, showing elimination of serum HBV DNA and HBsAg values. Serological investigation of all family members and information from the transplantation unit did not reveal the infection source. Conclusion:de novo Hepatitis B in liver recipients is a rare phenomenon. In donor positive anti-HBc cases, it appears as reactivation of HBV infection. There are very few published cases in which recipients developed de novo HBV hepatitis, despite seronegative HBcAb donors. Caregivers should always be alert for de novo hepatitis B in liver transplanted children as loss of immunity could be an unexpected phenomenon, despite pre-transplant negative serology of the donor and recipient as so as despite seroprotective Abs titers after immunisation of the recipient.

Covid-19: Face Mask Protection in the Pediatric Setting.

We report our experience regarding a pediatric patient-case who had a covid-19 infection, which was initially considered a common viral infection and was managed accordingly for the first 36 hours while being hospitalized. Wearing a simple surgical face mask was the only protective measure which our personnel has adopted. All staff members were tested for covid-19 infection with swab specimens from the nasopharynx and pharynx and were found to be negative in 7-10 days after coming into contact with the patient. Thirty-one days after contact with the covid-19 patient, no one of the staff members had respiratory symptoms, and therefore, they all returned to work. This case shows the importance of face-mask wearing to prevent the transmission various of respiratory infections, including that caused by the novel SARS-CoV-2 microorganism.

Diet Quality: A Neglected Parameter in Children With Food Allergies. A Cross-Sectional Study.

Background-Objective: With recent evidence suggesting that growth is no longer considered a major issue in children with food allergies (FA) on elimination diet, priority has shifted to diet quality to establish healthy eating patterns and prevent non-communicable diseases. The Diet Quality Index - International (DQI-I) could be useful for assessing the overall diet quality of FA-children. This study aimed to evaluate the impact of elimination diet on DQI-I in children with FA and the accuracy of DQI-I in reflecting nutrient intake. Materials-methods: In a prospective, cross-sectional, cohort study of FA-children (2-14 years), nutritional intake was evaluated using a 7-day food frequency questionnaire, 24-h dietary recall, and the DQI-I. Results: Of the 76 children recruited, 44.7% had multiple allergies. Mean overall DQI-I score was 52 points, with only 28% of participants having good overall DQI-I (≥60 points). DQI-I moderation and balance were the most affected domains. Participants with multiple allergies had higher DQI-I moderation and balance and lower vitamin D and Ca intake. Compared to toddlers, schoolchildren had higher DQI-I variety and lower moderation and received higher vitamin B2, vitamin B12, Ca, P, and Zn. The number of allergies, age, and milk avoidance were independently associated with adjusted DQI-I moderation and balance, energy, and certain micronutrient intake. Higher percentages of participants with good DQI-I received adequate amounts of Mn and vitamins A, B6, C, and folate than those with poor DQI-I. Conclusions: In children with FA on elimination diet, the DQI-I accurately captured the deflection of diet quality related to the development of chronic, non-communicable diseases through its moderation and balance components. This is DQI-I's main purpose as a healthy diet indicator and as such it would be a useful tool responding to the needs of the contemporary shifting of priorities in FA-children's diet from quantity to quality. Nevertheless, it does not accurately reflect the intake of certain micronutrients potentially compromised by elimination diets. Therefore, regular nutritional assessment utilizing both the DQI-I and tools assessing individual nutrient intakes along with professional nutrition counseling should be integral parts of the individualized management of children with FA to ensure adequate nutrient intake and establish healthy dietary patterns.

Tacrolimus Immunosuppression Causes Drug-Induced Hypersensitivity Reactions in Liver-Transplant Patients: A 3-Case Report.

BACKGROUND: Drug-induced hypersensitivity reactions attributed to the immunosuppressive agent tacrolimus after an organ transplant are rare in the literature. We present 3 cases of male adult patients grafted with a cadaveric liver who developed delayed hypersensitivity reactions to tacrolimus in the form of the prolonged-release capsules (Advagraf). Furthermore, the appropriate drug concentration solutions used for allergy testing are proposed. METHODS: All patients received a liver transplant (LT) because of cirrhosis of various etiologies. They were immunosuppressed with tacrolimus once daily. Several months after they had been placed on an immunosuppressive regimen with tacrolimus in the form of prolonged-release capsules (Advagraf), the patients presented with delayed hypersensitivity reactions and torturous pruritic rash that affected the whole body and was unresponsive to treatment with oral ursodeoxycholic acid, cholestyramine, or levocetirizine. Allergy testing that was performed by skin prick testing was negative. Nevertheless, intradermal testing yielded positive results in all 3 patients. Management was by interruption of the culprit agent, which was followed by symptom resolution. The immunosuppressive treatment was continued with alternative drugs. RESULTS: Appropriate nonirritating drug concentration solutions of the drug used for intradermal testing were highly sensitive and confirmed the clinical diagnosis of tacrolimus allergy in all the affected patients. CONCLUSION: Immunosuppressive treatment with tacrolimus in the form of prolonged-release capsules may cause a drug hypersensitivity reaction. A suspicion of allergy warrants a referral for allergy testing. Pruritic rash refractory to treatment in liver transplanted patients should be evaluated by an allergist for possible drug allergy when bile stasis and graft disease have been excluded. Intradermal testing has proven a highly sensitive method for confirming a drug allergy diagnosis, whereas skin prick testing did not.

Association of IL-10 gene promoter polymorphisms with food allergy susceptibility and serum IL-10 level in a pediatric Caucasian population.

BACKGROUND: Interleukin 10 has been shown to play a critical role in the regulation of the immune responses in allergic diseases. AIM: To investigate if genetic polymorphisms in the promoter region of the IL-10 gene are associated with food allergy (FA) susceptibility in Caucasian pediatric patients with concomitant allergic diseases and IL-10 levels. METHODS: The single nucleotide polymorphisms (SNPs) at -1082A > G (rs1800896), -819 T > C (rs1800871), and -592A > C (rs1800872) of 62 pediatric patients with IgE-mediated FA were analyzed and correlated with clinical parameters, serum IgE and IL-10 levels. The results were compared with those of 92 healthy controls without FA, personal and/or family history of atopy. RESULTS: Analysis and comparison of genotype distributions, allele frequencies, and haplotypes showed that none of the genotypes confers an increased risk of FA. The genotype -1082 AA in FA patients was associated with moderate to severe symptoms of FA, the development of atopic asthma, and higher levels of IL-10. In a linear regression study, we confirmed that the genotype -1082 AA acts as an independent factor for the higher levels of IL-10. A positive association was also observed between -819T/C and -592 A/C SNPs and later onset of FA. CONCLUSION: Polymorphisms in the promoter region of the IL-10 gene are not associated with FA susceptibility in our cohort. In FA patients, -1082 A/G SNPs seem to influence the production of IL-10, the severity of FA symptoms, and the development of atopic asthma in this population.

Inflammatory Bowel Disease in Children and Adolescents - a Retrospective Study of 13 Years of Records Investigating Potential Prognostic Factors.

Purpose: To assess the landscape of management of pediatric inflammatory bowel disease (IBD) patients in Greece and investigate possible prognostic factors for the disease outcome. Method: The medical records of all IBD patients who visited the gastroenterology divisions of two university pediatric clinics as in- or outpatients over 13 years were examined. Results: Twenty-seven females and 25 males were included in the study. Ulcerative colitis (UC) was diagnosed in 46% of cases, Crohn's Disease (CD) in 33% and unclassified IBD (IBD-U) remained the diagnosis in 21%. The CRP level was elevated in 68% of cases at diagnosis, whereas only 27.4% of patients had ESR levels and platelet counts within the age-adjusted normal range. No parameter derived from patient history, physical examination or laboratory and imaging was found to influence the time to diagnosis. Abdominal pain and lack of diarrhea at the time of diagnosis were significantly associated with the need for biologic therapy during the disease course in CD. Consistent with the "step-up" approach the treating physicians practiced, an increased number of relapses correlated with the addition of biologics in the treatment of both CD and UC patients (P=.03 and P=.002, respectively). Conclusion: It is the first time that clinical data regarding IBD pediatric patients in Greece were reviewed. Some clinical and imaging factors were associated with more aggressive disease, an increased need for biological treatment and frequent hospitalizations for IBD flares. Moreover, it was observed that the clinical features of IBD in Greek children were similar to those in other countries.

Trichohepatoenteric syndrome: A rare mutation in SKIV2L gene in the first Balkan reported case.

Trichohepatoenteric syndrome or syndromic diarrhea is a rare and severe Mendelian autosomal recessive syndrome characterized by intractable diarrhea, facial and hair abnormalities, liver dysfunction, immunodeficiency and failure to thrive. It has been associated with mutations in TTC37 and SKIV2L genes, which encode proteins of the SKI complex that contributes to the cytosolic degradation of the messenger RNA by the cell's exosome. We report a case of a male infant who suffered from typical symptoms and signs of trichohepatoenteric syndrome without immunodeficiency. The patient's genetic testing showed a very rare mutation in SKIV2L gene's 25 exons (p.Glu1038 fs*7 (c.3112_3140del)). Even though our patient was provided with total parenteral nutrition from birth, the child's death in the third year of age highlights the severity of the disease and the poor prognosis of this particular type of genetic predisposition.

A Synbiotic Infant Formula with High Magnesium Content Improves Constipation and Quality of Life.

PURPOSE: To evaluate the efficacy of synbiotic formula with partial whey hydrolysate and high magnesium content in infants presenting with functional constipation. METHODS: Sixty-five infants with functional constipation were included. Forty infants were treated during one month with parental reassurance and the intervention formula and were compared to a control group of 25 infants treated with parental reassurance only. Parents completed a quality of life (QoL) questionnaire at baseline and during the last week of the study. RESULTS: At inclusion, stool characteristics and QoL were similar in both groups. The control group was slightly older than the intervention group (7.5±3.9 vs. 6.2±3.6 weeks). At onset, stool composition was "hard and tight" (Bristol stool scale 1 and 2) in all infants. After one month, stool composition remained unchanged in the control group except in two infants that developed "creamy" stools (Bristol stool scale type 3 and 4). In the intervention group, stools remained "hard and tight" in 27.5%, and became "creamy" in 47.5%, "loose" (Bristol stool scale type 5) in 22.5% and "watery" (Bristol stool type 6 and 7) in 2.5%. The benefit of the intervention formula was estimated to be "very important" in 70%. The median scores for QoL improved significantly in the intervention group for all parameters and for one in the control group. CONCLUSION: The intervention formula significantly improved functional constipation resulting in a better QoL of the parents and infants.

Safety of a New Synbiotic Starter Formula.

PURPOSE: Breastfeeding is the best way to feed all infants, but not all infants can be (exclusively) breastfed. Cow's milk based infant formula is the second choice infant feeding. METHODS: The safety of a new synbiotic infant formula, supplemented with Bifidobacterium lactis and fructo-oligosaccharides, with lactose and a whey/casein 60/40 protein ratio was tested in 280 infants during 3 months. RESULTS: The median age of the infants at inclusion was 0.89 months. Weight evolution was in accordance with the World Health Organization growth charts for exclusive breastfed infants. The evolution of all anthropometric parameters (weight-for-length z score and body mass index-for-age z score) was within the normal range. The incidence of functional constipation (3.2%), daily regurgitation (10.9%), infantile crying and colic (10.5%) were all significantly lower than the reported median prevalence for a similar age according to literature (median value of 7.8% for functional constipation, 26.7% for regurgitation, 17.7% for infantile colic). CONCLUSION: The new synbiotic infant starter formula was safe, resulted in normal growth and was well tolerated. Functional gastro-intestinal manifestations (functional constipation, regurgitation and colic) were significantly lower than reported in literature. Synbiotics (Bifidobacterium lactis and fructo-oligosaccharides) in cow's milk based infant formula bring the second choice infant feeding, formula, closer to the golden standard, exclusive breastfeeding.

Corrigendum: Subcutaneous and Sublingual Immunotherapy in Allergic Asthma in Children.

[This corrects the article on p. 82 in vol. 5, PMID: 28484690.].

Innovative Dietary Intervention Answers to Baby Colic.

PURPOSE: The purpose of this paper is to evaluate the efficacy of a lactose- reduced synbiotic partial whey hydrolysate in formula fed infants presenting with colic and the impact of this dietary intervention in mean crying time and quality of life. METHODS: Forty infants with infantile colic were treated during one month with parental reassurance and the intervention formula (partial whey hydrolysate, reduced lactose, Bifidobacterium lactis BB12 and galacto-oligosaccharides) and were compared to a control group of 20 infants with infantile colic treated with parental reassurance and a standard infant formula. Parents completed a quality of life (QoL) questionnaire assessing the burden of infantile colic. Wilcoxon test, t-test and Mann-Whitney test were used to compare QoL scores before and after intervention as well as between the intervention and control group. RESULTS: At inclusion, duration of crying did not differ between both groups. Crying duration decreased with 2.7 hours (from 3.2 to 0.5 hours) in the intervention group while duration of crying decreased only with 1.2 hours in the control group (p<0.001). Stool composition became looser in the intervention group, but defecation frequency did not change. The median scores of the QoL questionnaire improved significantly in the intervention group for all parameters. In the control group, parameters improved significantly also but not for the parent-child and social interaction. The score changes were significantly greater in the intervention than in the control group. CONCLUSION: The intervention formula (partial whey hydrolysate, synbiotic, reduced lactose) significantly reduced the duration of crying and improved QoL of the parents and infants.

Subcutaneous and Sublingual Immunotherapy in Allergic Asthma in Children.

This review presents up-to-date understanding of immunotherapy in the treatment of children with allergic asthma. The principal types of allergen immunotherapy (AIT) are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Both of them are indicated for patients with allergic rhinitis and/or asthma, who have evidence of clinically relevant allergen-specific IgE, and significant symptoms despite reasonable avoidance measures and/or maximal medical therapy. Studies have shown a significant decrease in asthma symptom scores and in the use of rescue medication, and a preventive effect on asthma onset. Although the safety profile of SLIT appears to be better than SCIT, the results of some studies and meta-analyses suggest that the efficacy of SCIT is better and that SCIT has an earlier onset than SLIT in children with allergic asthma. Severe, not controlled asthma, and medical error were the most frequent causes of SCIT-induced adverse events.