Molecular Diagnosis in House Dust Mite-Allergic Patients Suggests That Der p 23 Is Clinically Relevant in Asthmatic Children.

BACKGROUND: Patterns of sensitization to house dust mites depend on geographic area and are important in clinical practice. However, the role of molecular diagnosis is not currently defined. We sought to characterize a pediatric population by focusing on sensitization to different mite species and major mite components in order to assess the clinical relevance of sensitization to allergenic components in our practice. METHODS: Consecutive children with respiratory allergy sensitized to house dust mites (determined by skin prick test [SPT]) were recruited. We determined specific IgE to nDer p 1, rDer p 2, and rDer p 23 using ImmunoCAP and sIgE using ImmunoCAP-ISAC microarray. Patients were followed up for 3 years. RESULTS: A total of 276 children were recruited. The frequency of sensitization was 86.6% for nDer p 1, 79.3% for rDer p 2, and 75.8% for rDer p 23. Lepidoglyphus species was the most common storage mite detected by SPT. Twenty-six patients (9.4%) were not sensitized to Der p 1 or Der p 2. It is noteworthy that IgE binding to Der p 23 was positive in 14 (53.8%). Asthmatic patients, especially those with a persistent moderate-severe phenotype, more frequently recognized the 3 major allergens. CONCLUSIONS: Most patients with mite allergy were sensitized to the major allergens Der p 1, Der p 2, and Der p 23. Of the allergens evaluated, 5% were sensitized to Der p 23 but not to Der p 1 or Der p 2. Sensitization to Der p 23 should be considered in the diagnosis and treatment of mite allergy, especially in patients with moderate-severe asthma, because it may worsen the clinical phenotype.

'Real-life' experience in asthmatic children treated with omalizumab up to six-years follow-up.

INTRODUCTION AND OBJECTIVES: Omalizumab is present in international guidelines for the control of severe asthma, but data on the long-term effects in children are limited. Our objective was to perform a 'real-life' long-term trial of omalizumab in children with allergic asthma. MATERIALS AND METHODS: An observational single center 'real-life' study was performed. Data for treatment, lung function, side effect, asthma exacerbations and hospitalizations were recorded at six months and annually. RESULTS: Forty-eight patients <18 years of age were enrolled. Median treatment period was 2.9 (0.5-6). Fluticasone dose for the maintenance treatment decreases significantly at six months (452mcg/day to 329.89mcg/day, respectively). This difference was maintained throughout the follow-up. Nobody used oral corticosteroid after six months. The rate of hospital admissions and visits to the emergency department for asthma exacerbations decreased significantly in the third years and fourth years follow-up, respectively. There was an improvement in lung function. Mean values of FEV1 and FEF25-75% before treatment were 79.88 and 62.94, respectively; after six months of treatment a statistically significant change was seen with a mean FEV1 of 92.29 and FEF25-75% of 76.31 (p=0.0001). Lung function values were above normal throughout the six years of treatment. No side effects were reported. CONCLUSIONS: Overall in 'real life' omalizumab in children reduces asthma exacerbations and hospitalizations, improves lung function, and decreases the maintenance therapy. It is shown to be safe for up to six years of treatment in children.

Humoral deficiency in three paediatric patients with genetic diseases.

BACKGROUND: Primary immunodeficiencies (PID) represent a heterogeneous group of genetic disorders characterised by poor or absent function in one or more components of the immune system. Humoral or antibody immunodeficiencies are the most common form of PID, of which common variable immunodeficiency (CVID) is the most frequent symptomatic form. CVID is usually characterised by hypogammaglobulinaemia with poor antibody specificity, and an increased susceptibility to infections, autoimmunity and lymphoproliferation. Fewer than 10% of CVID patients have a known monogenic basis. Several chromosomal abnormalities (chromosome 18q-syndrome, monosomy 22, trisomy 8 and trisomy 21) are currently identified as causes of hypogammaglobulinaemia, and can manifest with recurrent infections and mimic CVID. METHODS: Review of clinical charts and laboratory results of paediatric patients followed in the outpatient clinic of PID with a diagnosis of genetic disease and humoral immunodeficiency. RESULTS: Three patients with different genetic diseases (19p13.3 deletion, a ring 18 chromosome and Kabuki syndrome), were identified. During follow-up, they developed signs and symptoms suggestive of humoral deficiency mimicking CVID, despite which immunoglobulin levels were quantified with considerable delay with respect to symptoms onset, and specific management was subsequently delayed. CONCLUSIONS: Patients with genetic abnormalities and recurrent infections should be evaluated for hypogammaglobulinaemia. An early diagnosis of humoral deficiency can allow treatment optimisation to prevent complications and sequelae.

[Consensus-based approach for severe paediatric asthma in routine clinical practice]. / Consenso para el abordaje del asma grave pediátrica en la práctica clínica habitual.

INTRODUCTION: Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. MATERIAL AND METHODS: An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. RESULTS: Eleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. CONCLUSIONS: This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma.

[Hypersensitivity reactions to non-steroidal anti-inflammatory drugs and tolerance to alternative drugs]. / Reacciones de hipersensibilidad a antiinflamatorios no esteroideos y su tolerancia a fármacos alternativos.

INTRODUCTION: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) are the most common reactions to drugs. The prevalence varies from 0.6 to 5.7% in general population, but there are no data available in children. The aim of this study is to determine the frequency of patients diagnosed with hypersensitivity to NSAIDs, and describe their clinical characteristics, type of hypersensitivity, and tolerance to alternative drugs. METHODS: Retrospective study was conducted on children with suspected hypersensitivity to NSAIDs from January 2012 to December 2013. The diagnosis was confirmed by oral drug provocation test (DPT) to the drug involved in the group with a history of one episode, while in the group with a history of more than one episode with the same drug the diagnosis was based on clinical data. Subsequently, a DPT with acetylsalicylic acid (ASA) was done in order to classify hypersensitivity into selective or multiple. In those cases with a positive result, a DPT was performed with alternative drugs. RESULTS: Out of a total of 93 children studied, 26 were diagnosed with hypersensitivity to NSAIDs: 7 confirmed by oral DPT, and 19 based on clinical data. Multiple hypersensitivity was diagnosed in 50% of patients. Ibuprofen was involved in all reactions. The most common clinical manifestation was angioedema (44%). Acetaminophen was the best tolerated alternative drug. CONCLUSIONS: More than one quarter (28%) of the population studied was diagnosed with hypersensitivity to NSAIDs, and 50% had multiple hypersensitivity. Acetaminophen is a safe alternative in children with hypersensitivity to NSAIDs. Meloxicam may be an alternative in cases that do not tolerate acetaminophen.

Tolerance to egg proteins in egg-sensitized infants without previous consumption.

BACKGROUND: 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. METHODS: One hundred and fifty-four infants up to 18 months, with cow's milk allergy (CMA) and/or atopic dermatitis (AD) without previous egg consumption, were recruited. SPT to EP were performed. If it was positive, sIgE was performed. If positive SPT and/or sIgE (n = 94), OFC was performed between 12 and 18 months. Receiver operating characteristic (ROC) curves were plotted, and the outcome of the OFC was related to SPT and sIgE. The cut-off points with the best diagnostic accuracy were found. RESULTS: Ninety-four patients were sensitized to egg (69%) and 60 nonsensitized (31%). Of the sensitized, 27 tolerated cooked (CE) and raw egg (RE) (28.7%). Sixty-seven were allergic (71.3%): 29 reacted to CE, seven to egg yolk (EY) and 22 to egg white (EW) and 38 reacted to RE. 69.2% tolerated CE. EW SPT and ovalbumin (OVA) sIgE have the best area under the curve (AUC). The higher positive predictive values (PPV) were obtained for EW SPT and EW sIgE. CONCLUSIONS: In egg-sensitized infants with EW SPT ≥8 mm and/or EW sIgE ≥8.36 KU/l, egg diagnostic OFC can be avoided as there is 94% probability of becoming positive. In the other patients, OFC should be performed safely and early to avoid unnecessary diets.

Novel and atypical splicing mutation in a compound heterozygous UNC13D defect presenting in Familial Hemophagocytic Lymphohistiocytosis triggered by EBV infection.

Familial Hemophagocytic Lymphohistiocytosis type 3 (FHL3) is a genetic disorder caused by mutations in UNC13D gene, coding the granule priming factor Munc13-4 that intervenes in NK and T cell cytotoxic function. Here we report the case of a 17-month-old girl with prolonged symptomatic EBV infectious mononucleosis and clinical symptoms of hemophagocytic syndrome. In vitro functional analysis pointed to a degranulation defect. The genetic analysis of UNC13D gene identified initially a heterozygous mutation (c.753+1G>T) in the donor splice-site that resulted in exon 9 skipping (maternal allele). Mutations in other genes were considered, but additional analysis of UNC13D cDNA revealed in the paternal allele a heterozygous transition from G to A (c.2448-13G>A) at the 3' acceptor splice-site in intron 25, generating a new acceptor splice-site that leads to a frameshift and a premature STOP codon. Allele specific amplification of the cDNA confirmed the absence of a functional mRNA from the paternal allele. This case illustrates an atypical compound heterozygous UNC13D mutation affecting the RNA splicing that generates a typical FHL3 phenotype.

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

BACKGROUND: Accurate predictors of natural tolerance development to cooked and uncooked egg are needed in egg-allergic patients. OBJECTIVE: To compare the diagnostic performance of different immunological tests in relation to egg allergy versus tolerance. METHODS: Children aged 5-18 years diagnosed with IgE-mediated egg allergy were prospectively recruited. All followed an egg-free diet. Prick test and specific IgE (sIgE) to ovalbumin, ovomucoid and egg white, ovalbumin-sIgG4 and ovomucoid-sIgG4 were determined. By boiled and raw egg challenges, children were classified as cooked egg allergic (CEA, n = 50) or tolerant (CET, n = 35), and uncooked egg allergic (UEA, n = 64) or tolerant (UET, n = 21). Statistics. Comparative analysis (CEA vs. CET and UEA vs. UET). Multivariate logistic regression. Partial receiver operating characteristic curve analysis of tests in relation to CEA and UEA. Negative decision points were defined as cut-offs with sensitivity 95%. RESULTS: Ovalbumin-sIgG4 resulted an independent protective factor for uncooked egg allergy. To identify patients with high probability of egg tolerance, ovalbumin-sIgE/sIgG4 tended to perform better than sIgE and prick, specifically in children with ovalbumin-sIgE < 1.9 kU/L (for UEA) and ovomucoid-sIgE < 2.12 kU/L (for CEA). The most accurate cut-offs to recommend challenges were ovalbumin-sIgE/sIgG4 below 2.49 for cooked egg and 1.45 for uncooked egg, which associated 89.5% and 80% probability of tolerance (negative likelihood ratios 0.08 and 0.06), respectively. These cut-offs identified correctly as tolerant an additional 23% and 14% of children with negative challenges to cooked and uncooked egg, respectively, in comparison with sIgE negative decision points. Additionally, prick test tended to perform better than sIgE alone in predicting cooked and uncooked egg tolerance for ovomucoid-sIgE < 0.92 kU/L and ovalbumin-sIgE < 1.37 kU/L, respectively. CONCLUSIONS: Ovalbumin-specific IgG4 is an independent predictor of tolerance development to uncooked egg. Ovalbumin-sIgE/sIgG4 ratio, followed by skin prick test (SPT), seems to perform better than sIgE in identifying egg-allergic children with high probability of tolerance to cooked and uncooked egg over follow-up.

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.

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

BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergy but dose-related reactions are common. OBJECTIVE: To evaluate safety of egg-OIT. To identify predictors of dose-related reactions. METHODS: Fifty children aged 5-18 underwent egg-OIT after confirming IgE-mediated egg allergy by double-blind placebo-controlled challenge (DBPCFC). All dose-related reactions over a median period of 18 months on-OIT (range: 12-28) were registered. Children were retrospectively divided into three subgroups: (1) children who stopped reacting to OIT-doses over time (RR, Resolved Reactions); (2) children with ongoing dose-related reactions over the whole period on-OIT (PR, Persistent Reactions); (3) children who discontinued OIT within induction phase due to frequent reactions not improved by protocol re-adaptation and medication (ED, Early Discontinuation). Baseline clinical/immunological parameters associated with subgroups were investigated. RESULTS: Reactions occurred in 7.6% of doses. Adrenaline was required in 26% of children. The three subgroups corresponded to three different safety phenotypes: (1) twenty-four children (48%, RR) experienced infrequent and mainly mild reactions that resolved over time. None required adrenaline; (2) seventeen children (34%, PR) experienced more frequent and severe ongoing reactions over time; (3) nine children (18%, ED) discontinued OIT due to very frequent and mainly moderate reactions. Early discontinuation was associated with underlying asthma, higher specific IgE (sIgE) and lower threshold at DBPCFC. In contrast, lower sIgE and less severe reactions at DBPCFC were associated with subgroup RR. sIgE showed excellent performance in predicting belonging to subgroup RR. Levels below the optimal cut-off (ovomucoid-sIgE 8.85 kU/L) indicated 77% probability of belonging to subgroup RR, whereas levels above it indicated 95% probability of early discontinuation or ongoing reactions over time. CONCLUSIONS AND CLINICAL RELEVANCE: Egg-OIT involves substantial risks. However, baseline parameters, particularly sIgE, may help identify children in whom the procedure is more likely to be safe. Egg-OIT safety needs improvement in children with more severe and persistent egg allergy.

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.

Position document: IgE-mediated allergy to egg protein.

Egg is the food that most often causes allergy in young Spanish children, with an incidence of 2.4-2.6% in the first 2 years of life. The prevalence of sensitisation and allergy to egg is greater in children with allergy to cow's milk and in those suffering atopic dermatitis. The protein component from egg white is the cause of the allergic response in child. The major allergens in egg white are ovomucoid and ovalbumin. Most of the allergic reactions affect the skin, followed by gastrointestinal and respiratory systems. Egg allergy is one of the most common causes of severe anaphylaxis. The diagnosis of egg allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which represents the gold standard for confirming the diagnosis. The treatment of egg allergy is based on the avoidance of egg protein intake. A subgroup of egg-allergic patients are tolerant to cooked egg. In these cases, only uncooked egg must necessarily be avoided. Maintaining a diet with strict egg avoidance is difficult, and transgressions are relatively common. The patient, family, and school environment should receive education and training in the avoidance of egg and in the management of possible allergic reactions. With an avoidance diet, up to 15-20% of children will remain allergic and the severity of the reactions will increase over the years. In these more severe cases of egg-allergy, it becomes more difficult to adhere to the avoidance diet over the years, with a significant decrease in patient quality of life. Oral tolerance induction can be regarded as a therapeutic option for IgE-mediated egg allergy. The anti-IgE, omalizumab, might become another genuine therapeutic option for food allergy, not only to prevent allergic reactions after a contact with egg, but also as a complementary treatment to oral tolerance induction for egg allergy, with the purpose of reducing adverse reactions. The administration of influenza vaccine to children with egg allergy is safe in children that do not manifest severe reactions after egg intake, and in children who tolerate cooked egg. The triple viral vaccine (MMR) can be given to egg-allergic children in their usual vaccination centre, with no added risk. Different medicinal products can be formulated with egg proteins, and therefore should be avoided in children with egg allergy.

[Clinical phenotypes associated with selective IgA deficiency: a review of 330 cases and a proposed follow-up protocol]. / Fenotipos clínicos asociados a la deficiencia selectiva de IgA: revisión de 330 casos y propuesta de un protocolo de seguimiento.

UNLABELLED: Selective IgA deficiency is the most common Primary Immune Deficiency. Only a small proportion of these patients present during childhood, but this proportion increases over the years, and may be associated with an IgG subclass deficiency with increased susceptibility to respiratory and digestive tract infections. During childhood, IgA deficient patients may also refer to symptoms related to allergic and autoimmune diseases or tumours. AIMS: To describe the relationship of selective IgA deficiency with infections, allergic diseases, autoimmune disorders and tumours. To investigate the presence of other immune disorders associated with selective IgA deficiency. To suggest a follow-up protocol for these patients. METHODS: Retrospective study of paediatric patients (<18 years) being followed-up in the Clinical Immunology Department between 1992 and 2007, as well as laboratory records with IgA values below 50mg/L. Clinical records were reviewed (frequency and intensity of diseases associated with selective IgA deficiency) along with immunology tests performed. RESULTS: A total of 330 paediatric patients were identified with a selective IgA deficiency: 39 (11.8%) suffered from recurrent ear infections (2 developed secondary deafness), 58 (17.5%) from recurrent upper respiratory tract infections, and 20 patients (6%) from recurrent pneumonia, 6 of whom developed secondary bronchiectasis and 2 underwent a lobectomy. A relationship with atopic disease was found in 62 (18.78%) of patients. Regarding digestive disorders, chronic diarrhoea was found in 21 (6.5%), coeliac disease in 22 (6.6%), and persistently high plasma transaminases in 3. Autoimmune manifestations were found in 38 (11.5%), juvenile chronic arthritis, type 1 diabetes, vitiligo, cytopenia, and Crohn's disease, amongst others). Tumours were identified in 5 (1.5%). An IgG sub-class deficiency was found in 5 patients (4%), and 6 patients had a confirmed deficiency in antibody production. CONCLUSIONS: In our cohort, 56.6% of patients with IgA deficiency showed other comorbidities which were, in decreasing frequency: recurrent infections (respiratory and ear infections), allergic diseases, autoimmunity and tumours. Some patients will develop a more severe humoral defect (IgG subclass deficiency with or without antibody deficiency).

Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy.

BACKGROUND: Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of oral desensitization in 2-year-old children with cow's milk allergy, as a treatment alternative to elimination diet. METHODS: A total of 60 children aged 24-36 months with IgE-mediated allergy to CMPs were included in this multi-center study and were randomized into two groups. Thirty children (group A: treatment group) began oral desensitization immediately, whereas the remaining 30 (group B: control group) were kept on a milk-free diet and followed-up for 1 year. RESULTS: After 1-year follow-up period, 90% of the children in group A had become completely tolerant vs. 23% of the children in group B. In group A, cow's milk skin reactivity and serum-specific IgE to milk and casein decreased significantly from the initial assessment, whereas group B showed no significant change after 1 year of follow-up. Twenty-four patients (80%) developed some reaction during the treatment period: 14 children developed moderate reaction (47%) and 10 mild reaction (33%). The most common manifestations were urticaria-angioedema, followed by cough. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, oral desensitization was found to be effective in a significant percentage of 2-year-old children with cow's milk allergy. Oral desensitization appears to be efficacious as an alternative to elimination diet in the treatment of 2-year-old children with cow's milk allergy. The side-effect profile appears acceptable but requires further study.

Allergic proctocolitis, food-induced enterocolitis: immune mechanisms, diagnosis and treatment.

The term food allergy refers to the immune reaction (mediated by IgE or otherwise) that develops in response to the ingestion of a concrete type of food. Among the different potential manifestations of an allergic reaction, those exclusively affecting the gastrointestinal system are described. In recent years, the study of non-IgE-mediated food allergy has grown in relevance. These disorders are almost always of a transient nature, inherent to (though not exclusive of) nursing infants, and with gastrointestinal symptoms that may have variable repercussions upon the nutritional state of the patient. The prevalence of such reactions is not known, though some studies report that up to 60 % of all cases of allergy to cow's milk proteins (CMPs) are due to non-IgE-mediated mechanisms. The latency period between the time of ingestion and the appearance of the first clinical manifestations is greater than in the case of IgE-mediated reactions, and the underlying immunopathological mechanism has not been clearly established although it is accepted that T cell mediation is involved. The gastrointestinal problems derived from these delayed or chronic reactions comprise allergic proctocolitis, enterocolitis and food protein enteropathies. These digestive disorders tend to appear in the first months of life, and are of a progressive and generally self-limiting nature, with resolution at about two years of age. The most commonly implicated food is milk and, in our setting, there have also been reports implicating fish, egg and rice although such reactions can be triggered by any protein introduced into the infant diet. These manifestations disappear after removing the causal protein from the diet. When the causal proteins are CMPs, a highly hydrolysed infant formula is supplied as substitute, and if the latter is not tolerated, an elemental amino acid-based formula is prescribed.

The predictive value of specific immunoglobulin E levels in serum for the outcome of the development of tolerance in cow's milk allergy.

BACKGROUND: Immunoglobulin E-mediated allergy to cow's milk protein (CMP) tends to subside over years of follow-up. The gold standard for detecting such allergy has been the oral challenge test. The development of some other test for determining the correct timing of the oral challenge test would avoid unnecessary patient discomfort. The aim of this study was to determine whether monitoring cow's milk (CM) specific IgE levels over time can be used as a predictor for determining when patients develop clinical tolerance. METHODS: A prospective 4-year follow-up study was made of 170 patients with IgE-mediated allergy to CMP, involving periodic evaluations (12, 18, 24, 36 and 48 months) with the determination of casein and CM specific IgE on each visit, along with CM challenge testing. ROC curves were used to analyse the sensitivity, specificity and predictive values of the casein and CM specific IgE levels versus the challenge test outcomes at the different moments of follow-up. RESULTS: In the course of follow-up, 140 infants (82 %) became tolerant. Specific IgE levels to CM: 2.58, 2.5, 2.7, 2.26, 5 kU(A)/l and to casein: 0.97, 1.22, 3, 2.39, 2.73 kU(A)/l, respectively, predicted clinical reactivity (greatest diagnostic efficiency values) at the different analysed moments of follow-up (12, 18, 24, 36 and 48 months). CONCLUSIONS: Quantification of CMP specific IgE is a useful test for diagnosing symptomatic allergy to CM in the paediatric population, and could eliminate the need to perform oral challenges tests in a significant number of children.