M. A. Martín-Mateos

Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test

Strict avoidance is the only accepted management for cows milk (CM) allergy. CM oral immunotherapy (CM‐OIT) is under investigation.

Baseline specific IgE levels are useful to predict safety of oral immunotherapy in egg-allergic children.

Oral immunotherapy (OIT) is a promising treatment for food allergy but dose‐related reactions are common.

Ovalbumin-specific IgE/IgG4 ratio might improve the prediction of cooked and uncooked egg tolerance development in egg-allergic children

Accurate predictors of natural tolerance development to cooked and uncooked egg are needed in egg‐allergic patients.

Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population

There are few studies on eosinophilic esophagitis (EE) in the pediatric population in Europe. We present our data and emphasize the following findings: a) all patients had symptoms of allergic respiratory disease prior to receiving a diagnosis of EE with polysensitization (aeroallergens, food allergens); and b) in contrast with the results of earlier studies, food sensitization in our series most often corresponded to legumes.

Tolerance to egg proteins in egg‐sensitized infants without previous consumption

Egg‐sensitized infants who have never eaten egg may react at first ingestion. We sought to determine the association between skin prick test (SPT) and specific IgE (sIgE) to egg proteins (EP) and oral food challenge (OFC) outcomes to find cut‐off points which can diagnose egg allergy.

Monoclonal antibodies in Pediatrics: use in prevention and treatment

An update is provided on monoclonal antibodies (MAbs): concept, production, indications for the diagnosis and treatment of neoplastic diseases and autoimmune disorders, prevention of transplant rejection, and treatment of allergic diseases, autoimmune disease and other noninflammatory disorders such as coronary disease. Mention is also made of MAb use in the prevention of respiratory syncytial virus (RSV) infection. A more extensive account is provided of the use of MAb in B cell lymphomas (anti-CD20) and T cell leukemias (anti-IL-2 R). Likewise, mention is made of the use of MAbs in autoimmune disorders, such as anti-TNF-alfa in application to chronic arthritis, Crohns disease and psoriasis, anti-C5 in the treatment of chronic arthritis, uveitis, systemic lupus erythematosus, and autoimmune hemolytic anemia. Anti-KT 3 MAb is used to treat acute rejection and graft versus host disease, while anti-IL-2 R alfa and anti-IL-2 R gamma are used for the prevention of acute transplant rejection. Anti-IgE MAb (omalizumab) is used to treat asthma and allergic rhinitis refractory to other treatments. Anti-L5 (mepolizumab), anti-IL-4, anti-TNF and anti-inflammatory cytokine mediator MAbs all have indications in asthma and severe allergic rhinitis, and in intense atopic dermatitis refractory to other treatments. As to the MAbs used for the prevention of RSV infection, mention is made of anti-epitope A of the F protein of the virus.

Serum allergen-specific IgA is not associated with natural or induced tolerance to egg in children.

The role of specific IgA (sIgA) in oral immunotherapy (OIT) and natural tolerance to foods is poorly understood. We aimed to study serum sIgA in induced and natural tolerance to egg. Children aged 5–16 years diagnosed with IgE‐mediated egg allergy were recruited. After egg challenge, patients were classified as transient (TEA) or persistent (PEA) egg‐allergic. PEA children were further divided into oral immunotherapy (PEA‐OIT) or egg avoidance (PEA‐EA). Allergy/tolerance was reassessed 9–12 months later (T1) in PEA‐EA. Serum sIgA to ovalbumin and ovomucoid were determined at inclusion in all patients and repeated in PEA at T1. 21 TEA and 52 PEA children were recruited (28 PEA‐OIT, 24 PEA‐EA). Serum sIgA remained unchanged after OIT. TEA and PEA had similar serum sIgA. No specific trend on serum sIgA was observed in five PEA‐EA who developed natural tolerance over follow‐up. Thus, serum sIgA seems not to be associated with induced or natural egg tolerance.

A 10% liquid immunoglobulin preparation for intravenous use (Privigen®) in paediatric patients with primary immunodeficiencies and hypersensitivity to IVIG.

BACKGROUND The objective of this study was to evaluate safety and efficacy of Privigen®, a 10% intravenous immunoglobulin (IVIG), in a particular group of paediatric patients (highly sensitive to previous IVIG infusion) affected with Primary Immunodeficiencies (PID). MATERIAL AND METHODS Patients (n=8) from 3 to 17 years old diagnosed of PID who often suffered from adverse events related to the infusion to previous IVIG were switched to Privigen® in an open protocol. Data were prospectively collected regarding Privigen® administration: infusion, safety and efficacy. In parallel, data on safety and tolerance were retrospectively collected from medical charts regarding the previous 10% IVIG product used. RESULTS 50% of the patients required premedication with previous IVIG. At the end of the study none required premedication with Privigen®. The infusion rate was lower than that recommended by the manufacturer. All patients had suffered through adverse events during previous IVIG infusion being severe in three patients and recurrent in the rest. With Privigen® only three patients suffered from an adverse event (all cases were milder than previous related). Trough levels of IgG remained stable. None suffer from any episode of bacterial infection. CONCLUSION The present work shows that Privigen® was safe in a group of hypersensitive paediatric patients who did not tolerate the administration of a previous 10% liquid IVIG by using a particular infusion protocol slower than recommended. The number of adverse effects was smaller than published, and all cases were mild. No premedication was needed. Privigen® was also effective in this small group.

Association of Polymorphisms in IRAK1, IRAK4 and MyD88, and Severe Invasive Pneumococcal Disease.

Background: Severe invasive pneumococcal disease (SIPD) has high morbidity and mortality, conditioned by pneumococcus and host factors, such as Toll-like receptors and their Toll-IL1R common signaling pathway. The objectives of this study are (1) to correlate single nucleotide polymorphisms (SNPs) involved in some Toll-IL1R signaling pathway proteins (IRAK1, IRAK4, IRAKM and MyD88) with SIPD by comparing patients versus healthy controls. (2) To determine whether these SNPs influence SIPD outcome. Methods: Case–control prospective observational study: 60 pediatric patients with IPD and systemic inflammatory response syndrome, and 120 healthy volunteers. Well-known immunodeficiencies were excluded. Independent variables: SNPs genotypes and alleles. Other variables: demographic, previous infections, and clinical, analytical and microbiological evolution data. Results: We have detected significant disequilibrium of SNPs frequencies between SIPD patients and controls in rs1059701-CC (IRAK1; P = 0.0067), rs4251513-CC (IRAK4; P < 0.0001), rs1461567-T (IRAK4; P = 0.0158) and rs6853-AA (MyD88; P < 0.0001). SIPD patients showed significant association between: leukocytosis > 15,000/mmc and rs1059702-nonTT (IRAK1; P = 0.0460), pleuropneumonia and rs1624395-G (IRAKM; P = 0.0147), and rs1370128-C (IRAKM; P = 0.0055), sequelae, and rs4251513-nonGG (IRAK4; P = 0.0055), death and rs6853-nonAA (P = 0.0054) and rs6853-G (P = 0.0065; MyD88). Conclusions: This is the first study to show an association between SNPs in IRAK1, IRAK4 and MyD88, and the presence of SIPD. Our data showed that some SNPs may lead to a higher risk of developing SIPD while other are related with the outcome in SIPD patients. Following PIRO score (predisposition, insult, response, organ dysfunction), identifying SNPs predisposing to infectious diseases, such as SIPD might help stratify patients with severe infectious diseases and design specific treatments.

Lymphoma as presentation of common variable immunodeficiency

taxenes, platinum salts, L-asparaginase and monoclonal antibodies involving anaphylactic or anaphylactoid reactions. To date no desensitisation protocols have been published on third generation aromatase inhibitors like AN. In these case reports both patients referred late reactions to AN with mainly cutaneous symptoms. To clarify the underlying mechanism of these reactions, patch tests with 10 % AN in white petrolatum were performed with negative results. This could have several explanations: the fi nal responsible agent for the reaction could be a metabolite of AN; poor penetration of the drug into the epidermis; low drug concentration, use of inappropriate vehicle and immunosuppression state of patients. Although no immune mechanism could be proven in our patients, a desensitisation procedure was tried with success. This result reinforces the fact that desensitisation to drugs that induce delayed cutaneous hypersensitivity reactions is possible and safe, as we have observed many times in patients with HIV infection and delayed cutaneous reactions to cotrimoxazol.