Blood or skin: what is best in predicting cow's milk allergy diagnosis?

Summary: Cut-off values for both skin prick tests (SPT) and specific IgE (sIgE) levels for predicting cow´s milk allergy (CMA) diagnosis are not universally defined. This study is a retrospective analysis of consecutive children (0-18 years-old) with suspected CMA tested with SPT and sIgE for cow's milk (CM) and its fractions between 2016-2017. CMA diagnosis was defined by a positive oral food challenge or a highly suggestive clinical history of CMA and SPT and/or sIgE positive to CM and/or its fractions. One hundred and five patients were included, 58% males with a median age of 2.5 (P25-P75:1-6) years and the diagnosis was confirmed in 83 patients (79%). The variables associated with CMA diagnosis were SPT with CM (p minor 0,05) and casein (p minor 0,05) and all sIgE to CM and its fractions (alfa Lactalbumin, beta Lactoglobulin and casein; p minor 0,05 for all). Optimal cut39 off points (Youden's index) for CMA diagnosis were, for the mean wheal diameter, to CM milk of 4.5mm and to casein of 3mm. For sIgE levels the optimal cut-off points were: for CM of 4.36 kUA/L, alfa-lactalbumin of 1.6 kUA/L, beta-lactoglobulin of 1.7 kUA/L and for casein of 2.6 kUA/L. The role of SPT and sIgE levels to cow´s mlik and its fractions is unequivocal in CMA follow-up. Moreover, sIgE levels seem to be more discriminatory than SPT.

Non-steroidal anti-inflammatory drug hypersensitivity in children.

INTRODUCTION: There are rather few publications about hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAID) in the paediatric age. In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity. METHODS: We conducted a retrospective analysis of the clinical files from every patient under 18 years old who attended two Portuguese paediatric allergy outpatient clinics, from January 2009 to August 2014, due to a suspected NSAID hypersensitivity. RESULTS: We included 119 patients, with a median age of nine years (P25-P75: 5-14). Ibuprofen was the commonest implicated NSAID in the patients' reports (n=94-79%). After DPT, NSAID hypersensitivity was confirmed in nine (7.6%) patients, excluded in 93 (78.2%) and was inconclusive in 17 (14.3%). In the majority (n=95-79.8%), the reaction occurred in the first 24h after intake. Eighty-four patients (70.6%) reported only cutaneous manifestations and 18 (15.1%) had systemic symptoms. Anaphylaxis represented a relative risk to NSAID hypersensitivity confirmation. No association was found for atopy and the number of previous reactions. CONCLUSION: In our study, NSAID hypersensitivity was confirmed in a small proportion of the patients with a previous reported reaction. Ibuprofen was the most implicated drug with urticaria/angio-oedema as the commonest manifestation. Anaphylaxis was associated with confirmed drug hypersensitivity. The drug provocation test was essential to establish the diagnosis.

Evaluation and comparison of commercially available latex extracts for skin prick tests.

BACKGROUND: Crude latex extracts are commonly used in skin prick tests (SPT) for the diagnosis of natural rubber latex (NRL) allergy. Nevertheless, variations in protein and allergen composition between latex extracts from different manufacturers can hamper a correct diagnosis. OBJECTIVES: To analyze the heterogeneity of proteins and allergens in latex extracts from 7 different manufacturers and to assess its relevance in the diagnosis of latex allergy. METHODS: Seven latex SPT extracts were analyzed for protein content using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The 4 major allergens Hev b 1, Hev b 3, Hev b 5, and Hev b 6.02 were also quantified using enzyme immunoassay. All commercial extracts were tested for their in vitro allergenic capacity using microarray inhibition assays and for their ability to induce biological reactivity in latex-allergic patients undergoing SPT. RESULTS: The protein content of the extracts varied widely from 8.0 microg/mL to 526.5 microg/mL. SDS-PAGE revealed broad differences in protein profiles between the extracts. Marked variability in the contents of all 4 major allergens was observed, and Hev b 3 and Hev b 5 were undetectable in some extracts. Microarray inhibition assays and SPT demonstrated relevant differences in allergenic capacity between the extracts. CONCLUSIONS: The marked heterogeneity in protein and allergen content of latex extracts from different manufacturers could explain the broad spectrum of SPT results recorded. Our findings suggest that the extracts used for the diagnosis of latex allergy should be improved and standardized.

Different in vivo reactivity profile in health care workers and patients with spina bifida to internal and external latex glove surface-derived allergen extracts.

BACKGROUND: Allergy to natural rubber latex is a well-recognized health problem, especially among health care workers and patients with spina bifida. Despite latex sensitization being acquired in health institutions in both health care workers and patients with spina bifida, differences in allergen sensitization profiles have been described between these two risk groups. OBJECTIVE: To investigate the in vivo reactivity of health care workers and patients with spina bifida to extracts of internal and external surfaces of latex gloves and also to specific extracts enriched in major allergens for these risk groups. METHODS: Gloves from different manufacturers were used for protein extraction, and salt precipitation and hydrophobic interaction chromatography (HIC) were applied to obtain the enriched latex extracts. The major latex allergens were quantified by an enzyme immunoassay. The extracts obtained were tested in 14 volunteers using skin prick tests (SPT). RESULTS: Latex glove extracts enriched in the hydrophobic allergens that are most often seen in patients with spina bifida were obtained by selective precipitation, whereas HIC produced extracts enriched in the hydrophilic allergens commonly found in health care workers. The health care workers had positive SPTs to glove extracts from internal surfaces and to the hydrophilic allergen-enriched extracts. By contrast, patients with spina bifida had larger skin reactions both to external glove extracts and to the extracts enriched with the hydrophobic major allergens for this risk group. Despite the protein concentration of these extracts being less than half the concentration of the commercial extract, the weal-and-flare reactions were of similar magnitude. CONCLUSION: Using novel latex extracts, our study showed a different in vivo reactivity pattern in health care workers and in patients with spina bifida to extracts of the internal and external surfaces of gloves, which suggests that sensitization may occur by different routes of exposure, and that this influences the allergen reactivity profiles of these risk groups.

Drug provocation tests to betalactam antibiotics: experience in a paediatric setting

Background: Few studies have been performed in children with suspected betalactam allergy. We aimed to assess the role of the drug provocation test (DPT) with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. Methods: We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital, Portugal (January 2002 to April 2008) for a compatible history of allergic reaction to betalactam. All were submitted to a DPT. Children were proposed to perform skin tests (ST) to betalactam antibiotics followed by DPT. If they decline ST, a DPT with the culprit drug was performed. Results: We studied 161 children, 60% were boys, with a median age of 5 years old at the time of the DPT. Thirty-three patients (20.5%) had an immediate reaction and 33 (20.5%) a non-immediate reaction. The severity of the reported reactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8. DPT was positive in only one (3.4%) of the patients skin tested and in 11 (13.4%) of those not skin tested. The severity of the DPT reaction was low. Asthma and food allergy were associated with a positive DPT in the later group. Conclusions: DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical option in infants and pre-school children, where ST are painful and difficult to perform. Additional caution should be taken in children with asthma and food allergy

Drug provocation tests to betalactam antibiotics: experience in a paediatric setting.

BACKGROUND: Few studies have been performed in children with suspected betalactam allergy. We aimed to assess the role of the drug provocation test (DPT) with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. METHODS: We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital, Portugal (January 2002 to April 2008) for a compatible history of allergic reaction to betalactam. All were submitted to a DPT. Children were proposed to perform skin tests (ST) to betalactam antibiotics followed by DPT. If they decline ST, a DPT with the culprit drug was performed. RESULTS: We studied 161 children, 60% were boys, with a median age of 5 years old at the time of the DPT. Thirty-three patients (20.5%) had an immediate reaction and 33 (20.5%) a non-immediate reaction. The severity of the reported reactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8. DPT was positive in only one (3.4%) of the patients skin tested and in 11 (13.4%) of those not skin tested. The severity of the DPT reaction was low. Asthma and food allergy were associated with a positive DPT in the later group. CONCLUSIONS: DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical option in infants and pre-school children, where ST are painful and difficult to perform. Additional caution should be taken in children with asthma and food allergy.

Lung function and clinical risk factors for asthma in infants and young children with recurrent wheeze.

BACKGROUND: Although several risk factors for asthma have been identified in infants and young children with recurrent wheeze, the relevance of assessing lung function in this group remains unclear. Whether lung function is reduced during the first 2 years in recurrently wheezy children, with and without clinical risk factors for developing subsequent asthma (ie, parental asthma, personal history of allergic rhinitis, wheezing without colds and/or eosinophil level >4%) compared with healthy controls was assessed in this study. METHODS: Forced expiratory flows and volumes in steroid naïve young children with >or=3 episodes of physician confirmed wheeze and healthy controls, aged 8-20 months, were measured using the tidal and raised volume rapid thoracoabdominal compression manoeuvres. RESULTS: Technically acceptable results were obtained in 50 wheezy children and 30 controls using tidal rapid thoracoabdominal compression, and 44 wheezy children and 29 controls with the raised volume technique. After adjustment for sex, age, body length at test and maternal smoking, significant reductions in z scores for forced expiratory volume at 0.5 s (mean difference (95% CI) -1.0 (-1.5 to -0.5)), forced expired flow after 75% forced vital capacity (FVC) has been exhaled (FEF(25)) (-0.6 (-1.0 to -0.2)) and average forced expired flow over the mid 50% of FVC (FEF(25-75)) (-0.8 (-1.2 to -0.4)) were observed in those with recurrent wheeze compared with controls. Wheezy children with risk factors for asthma (n = 15) had significantly lower z scores for FVC (-0.7 (-1.4 to -0.04)) and FEF(25-75) (-0.6 (-1.2 to -0.1)) than those without such risk factors (n = 29). CONCLUSIONS: Compared with healthy controls, airway function is reduced in young children with recurrent wheeze, particularly those at risk for subsequent asthma. These findings provide further evidence for associations between clinical risk factors and impaired respiratory function in early life.