EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

Pre-hospital treatment of bee and wasp induced anaphylactic reactions: a retrospective study.

BACKGROUND: Bee and wasp stings are among the most common triggers of anaphylaxis in adults representing around 20% of fatal anaphylaxis from any cause. Data of pre-hospital treatment of bee and wasp induced anaphylactic reactions are sparse. This study aimed to estimate the incidence of bee and wasp induced anaphylactic reactions, the severity of the reactions and to correlate the pre-hospital treatment with the severity of the anaphylactic reaction. METHODS: Retrospective and descriptive study based on data from the Mobile Emergency Care Units (MECUs) in the Region of Southern Denmark (2008 only for Odense and 2009-2014 for the whole region). Discharge summaries with diagnosis related to anaphylaxis according to the International Classification of Diseases 10 (ICD-10) were reviewed to identify bee and wasp induced anaphylactic reactions. The severity of the anaphylactic reaction was assessed according to Sampson's severity score and Mueller's severity score. Treatment was evaluated in relation to administration of adrenaline, glucocorticoids and antihistamine. RESULTS: We identified 273 cases (Odense 2008 n = 14 and Region of Southern Denmark 2009-2014 n = 259) of bee and wasp induced anaphylaxis. The Incidence Rate was estimated to 35.8 cases per 1,000,000 person year (95% CI 25.9-48.2) in the Region of Southern Denmark during 2009-2014. According to Sampson's severity score, 65% (n = 177) of the cases were graded as moderate to severe anaphylaxis (grade 3-5). Almost one third of cases could not be graded according to Mueller's severity score. Adrenaline was administrated in 54% (96/177) of cases with moderate to severe anaphylaxis according to Sampson's severity score, compared to 88% receiving intravenous glucocorticoids (p < 0.001) and 91% receiving intravenous antihistamines (p < 0.001). Even in severe anaphylaxis (grade 5) adrenaline was administered in only 80% of the cases. CONCLUSION: Treatment with adrenaline is not administered in accordance with international guidelines. However, making an assessment of the severity of the anaphylactic reaction is difficult in retrospective studies.

Validation of the Global Allergy and Asthma European Network (GA2LEN) chamber for trials in allergy: Innovation of a mobile allergen exposure chamber.

BACKGROUND: Field clinical trials of pollen allergy are affected by the impossibility of predicting and determining individual allergen exposure because of many factors (eg, pollen season, atmospheric variations, pollutants, and lifestyles). Environmental exposure chambers, delivering a fixed amount of allergen in a controlled environmental setting, can overcome these limitations. Environmental exposure chambers are currently already used in phase 2, 3, and even 4 trials. Unfortunately, few chambers exist in the world, and this makes it difficult to perform large, multicenter clinical trials. The new Global Allergy and Asthma European Network (GA2LEN) mobile exposure chamber is a step forward because the mobility of the chamber makes it convenient for patients to participate in clinical testing. OBJECTIVE: This study was made to validate the reproducibility, sensitivity, and specificity of the results obtained in the new GA2LEN chamber. METHODS: Seventy-two adult patients (19-61 years old) with allergic rhinitis with or without asthma caused by grass pollen were included in different clinical validation tests. Total symptom scores and total nasal symptom scores were recorded at time zero (0) and every 10 minutes during exposures, along with nasal and respiratory parameters. RESULTS: Exposure tests confirmed the reproducibility between subsequent runs and the sensitivity (P < .00001 vs patients exposed to placebo) and specificity (very low score in nonallergic subjects) in the GA2LEN chamber. No adverse reactions were recorded during the tests. CONCLUSIONS: The mobility of the GA2LEN chamber provides a new, potentially effective, and safe way of generating reliable data in allergy multicenter clinical trials.

Decrease in the rate of sensitization and clinical allergy to natural rubber latex.

BACKGROUND: In the 1980s, a striking increase in natural rubber latex (NRL) allergy was seen. Since then, many measures have been taken to prevent NRL allergy. OBJECTIVES: To investigate changes in the prevalence of NRL sensitization/clinical NRL allergy over time from 2002 to 2013. METHODS: All patients prick tested for NRL at the Department of Dermatology and Allergy Centre, Odense University Hospital were included in this study (n = 8580). In NRL-sensitized patients, the clinical relevance was evaluated for NRL. Furthermore, concomitant positive prick test results for birch pollen were recorded, together with food-related symptoms and sensitization in a subgroup of patients. RESULTS: The prevalence of NRL sensitization declined from 6.1% in 2002-2005 to 1.9% in 2006-2009, and then to 1.2% in 2010-2013 (p < 0.0001). The prevalence of clinical NRL allergy declined from 1.3% in 2002-2005 to 0.5-0.6% in 2006-2013 (p < 0.004). Among the NRL-sensitized patients, 64% had a concomitant positive prick test reaction to birch pollen, and 52% had a history of reaction to oral intake of related fruits or vegetables. CONCLUSION: Our study showed a statistically significant decline in the number of patients sensitized/clinically allergic to NRL. Many of the NRL-sensitized patients without clinical allergy to NRL had concomitant birch pollen sensitization, and reported food-related symptoms.

Angioedema--assessment and treatment.

BACKGROUND: Angioedema has numerous hereditary, acquired and iatrogenic causes. A number of studies show that angioedema is inadequately assessed and treated during its acute phase as well as in the follow-up period. We present an algorithm for the assessment and treatment of patients with angioedema. KNOWLEDGE BASE: The article is based on a literature search in PubMed, a review of bibliographies and the authors' clinical experience and research. RESULTS: The majority of angioedema patients have accompanying urticaria. Pathophysiologically, angioedemas are divided into histaminergic and non-histaminergic forms. In a large group of patients no positive trigger is identified. On assessment in hospital the most frequently identified cause is drug intake, normally angiotensin-converting-enzyme inhibitors and NSAIDs , while allergic/pseudoallergic and idiopathic reactions are more commonly seen in general practice. There are a number of rare causes of angioedema, all of which are important to keep in mind. The acute and prophylactic treatment will depend on the subtype of angioedema and is best provided through cross-disciplinary collaboration. INTERPRETATION: Angioedema is a potentially life-threatening condition and should be assessed and treated systematically. It is important to remember that angioedema is either histaminergic or non-histaminergic, as the treatment of the two types is different.

Cutaneous adverse drug reactions seen at a university hospital department of dermatology.

Patients with suspected cutaneous adverse drug reactions are often referred to allergy clinics or departments of dermatology for evaluation. These patients are selected compared with patients identified in prospective and cross-sectional studies of hospital populations. This explains the observed variation in prevalence of specific reactions and of eliciting drugs. This study investigated the prevalence of cutaneous adverse drug reactions in a university hospital department of dermatology that is specially focused on allergy. An 8-month survey was carried out during the period April-December 2003. Consecutive patients suspected of having cutaneous adverse drug reactions during this period were examined by dermatologists and investigated. Drug imputability was assessed in the 194 patients included; 33.5% had an exanthema with certain or likely drug imputability. Urticaria and local reactions at injection sites were the most frequent reactions (25% and 18.8%, respectively). Beta-lactam antibiotics, extracts for desensitization and insulins were the main drug groups involved, and accounted for 22.8%, 17.1% and 14.2%, respectively, of the reactions. Extracts for desensitization and insulins elicited more reactions than expected. This probably reflects the referral pattern to an allergy clinic.

Anti-irritants II: Efficacy against cumulative irritation.

So-called anti-irritants (AI) are widely used in cosmetic formulations, with the aim of reducing irritation from substances in the formulation. It may also be claimed that they are 'soothing' and 'healing' ingredients. However, the proof for these claims is circumstantial. The dose-response effect of 4 alleged AI (nifedipine, (-)-alpha-bisabolol, canola oil and glycerol) was studied on experimentally induced acute irritation in healthy volunteers, and only glycerol showed dose-related response and effects potentially better than no treatment. The acute irritation model only allowed a small window of opportunity in which to demonstrate efficacy. Therefore, the effect of AI was studied in a cumulative irritation model by inducing irritant dermatitis with 10 min daily exposures for 5+4 days (no irritation on weekend) to 1% sodium lauryl sulfate on the right and 20% nonanoic acid on the left volar forearm. AI ointments were applied twice daily. Clinical scoring was performed daily, evaporimetry (Trans Epidermal Water Loss), hydration and colourimetry were measured at baseline (D0), in the middle and at the end of treatment. The glycerol ointment was the only treatment statistically better than both 'no treatment' and vehicle.

Anti-irritants I: Dose-response in acute irritation.

The term 'anti-irritant' (AI) was coined in 1965 by Goldemberg to describe a diverse group of topical product ingredients, which were able to reduce the irritation potential of other more irritating ingredients in the same product. 'AIs' are being added to cosmetic formulations in order, allegedly, to benefit tolerability of the products and allow claims such as 'soothing' and 'healing' ingredients. Limited documentation in favour of the efficacy of AIs is published. We studied the dose-related effect of 4 alleged AIs (nifedipine, (-)-alpha-bisabolol, canola oil and glycerol) on experimentally induced acute irritation in healthy volunteers. Each AI was used in 3 concentrations. Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate and 20% nonanoic acid in N-propanol. The irritant reactions were treated twice daily with AI-containing formulations from the time of removal of the patches. Evaluation of skin irritation and efficacy of treatments were performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colourimetry. Only glycerol showed dose-response and effects potentially better than no treatment. There was no significant effect and no difference between the three other AIs.

Food allergy to apple and specific immunotherapy with birch pollen.

Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present.

Immunochemical and biological quantification of peanut extract.

Biological standardization of allergen extracts is one of the steps in the characterization of an extract. The gold standard for determination of biological potency is the skin prick test, but histamine release (HR) has been used as a convenient ex vivo method for analyzing a large number of samples. We describe the use of rabbit basophils as a tool in biological standardization. Using peanut as a model allergen, it is described how rabbits immunized for production of antiserum may become sensitized and their basophils used for histamine release experiments. It is also possible to use rabbit antiserum to passively sensitize basophils derived from naive rabbits, but the sensitivity of this method is so far 100-1000 times lower than the direct histamine release. The rabbit histamine release results are compared to an ELISA developed by means of the same antisera and by passive sensitization of human basophils using serum from a strongly sensitized peanut-allergic patient. The overall sensitivity of the methods were ELISA > HR-human cells > HR-sensitized rabbit cells > HR-passively sensitized rabbit cells. The use of rabbit basophils for biological standardizations will allow for the use of rabbit antisera.