Background: Allergic rhinitis (AR), an IgE-mediated inflammatory disease, significantly impacts the quality of life of a considerable proportion of the general population. Omalizumab, a humanized monoclonal antibody against IgE, has been evaluated for both seasonal and perennial AR. We aimed to assess the efficacy and safety of omalizumab in randomized controlled trials (RCTs) in inadequately controlled AR. Methods: We conducted a systematic literature search of RCTs evaluating the safety and efficacy of omalizumab in AR. We synthesized evidence for clinical improvement of AR symptoms, quality of life, reduction of the use of rescue medication, and adverse events. Results: The systematic search returned 289 articles, of which 12 RCTs were eligible for data extraction and meta-analysis. Omalizumab reduced the Daily Nasal Symptom Severity Score (DNSSS) by a summary standardized mean difference of -0.41 points (95% CI: -0.61, -0.22; I2=93.2%), the Daily Ocular Symptom Severity Score (DOSSS) by a summary standardized mean difference of -0.30 points (95% CI: -0.50, -0.01; I2=86.2%), the Rhino-conjunctivitis Quality of Life Questionnaire by a summary standardized mean difference of -0.45 points (95% CI: -0.57, -0.34; I2=0%) and the mean daily consumption of rescue antihistamines by a summary standardized mean difference of -0.21 (95% CI: -0.41, -0.01; I2=85.7%). No statistically significant difference in the occurrence of adverse events was observed between omalizumab and placebo (Relative Risk 1.03; 95% CI: 0.93, 1.14; I2=43.3%). Conclusion: Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with conventional treatment.

Background Recommendations have been issued on healthy complementary feeding (CF) strategies for infants, to reduce food allergy. This is a study of routine guidance provided by Greek pediatricians on the timing of CF for healthy infants and those at high risk for allergy. Methods Pediatricians in Greece completed an anonymous online questionnaire covering demographic information and recommended CF, specifically the foods, preparation methods, supplements, time interval between introduction of new foods for infants at low and high risk for allergy, and foods delayed in the case of high allergy risk. Results The respondents (n=233) recommended introducing: at 6 months, fruits, starchy non-gluten-grains, vegetables, olive oil and meat; at 7 months, gluten-rich grains; at 8 months, yogurt, hard-boiled egg and legumes; at 8.5 months, fish; at 9 months, nuts. A longer interval between new foods (≥ 4 days) was recommended, for low-risk infants, by male pediatricians (p=0.04), and for infants at high risk of allergy, by pediatricians with no subspecialty (p<0.001) and those practicing in a rural/semi-urban area (p=0.002). Pediatric practice of < 15 years was a predictor for earlier introduction of egg, seafood, gluten-rich grains, legumes and nuts for infants at high risk of allergy, and parenthood and male sex for egg and grains. Conclusions Greek pediatricians use a food introduction schedule for CF of infants, and, although not explicitly recommended in current guidelines, they delay introduction of common food allergens and suggest longer time intervals between introduction of new foods, especially for infants at high risk of allergy.

Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for paediatric urticaria are implemented. Methods: The EAACI Taskforce for paediatric CU disseminated an online clinical survey among EAACI paediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centres. Results: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly paediatric allergists (80%) and paediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (e.g., autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2nd generation antihistamine as first- line treatment of whom 64.8% up dosed as a second- line. Omalizumab, was used as a second line treatment by 1.7% and third-line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). Conclusions: Even though most members of the Paediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re-evaluate, update and standardize guidelines on the diagnosis and management of CU in children.

Childhood rashes or exanthemas are common and are usually relatively benign. There are many causes of rash in children, including mainly viruses, and less often bacterial toxins, drugs, allergens, and other diseases. Viral exanthema often appears while children are taking a medication in the course of a viral infection; it can mimic drug exanthema, and is perceived as a drug allergy in 10% of cases. The drugs most commonly implicated are beta-lactams (BL) and nonsteroidal anti-inflammatory drugs (NSAIDs). Viruses, commonly Epstein Barr virus (EBV), human herpesvirus 6 (HHV6) and cytomegalovirus (CMV), and the bacterium Mycoplasma pneumoniae, may cause exanthema either from the infection itself (active or latent) or because of interaction with drugs that are taken simultaneously. Determination of the exact diagnosis requires a careful clinical history and thorough physical examination. Haematological and biochemical investigations and histology are not always helpful in differentiating between the two types of exanthema. Serology or polymerase chain reaction (PCR) can be helpful, although a concomitant acute infection does not exclude drug hypersensitivity. A drug provocation test (DPT), although considered the gold standard for the diagnosis, is not preferred by the patients. Skin tests are not well tolerated, and in vitro tests, such as the basophil activation test and lymphocyte transformation, are of low sensitivity and specificity and their relevance is debatable. Based on current evidence, we propose a systematic clinical approach for timely differential diagnosis and management of rashes in children who present a cutaneous eruption while receiving a drug.

Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited and spontaneously resolve within days after drug discontinuation, sometime HRs reactions to AEDs can be severe and life threatening. Aim: This paper seeks to show examples on practical management of AEDs HRs in children starting from a review of what it is already known in literature. Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications and genetic factors. The diagnosis work-up consists of in vivo (Intradermal testing and Patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays and granulysin (Grl) in flow cytometry]. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. Conclusion: Dealing with AEDs HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternate anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.