Intradermal Tests for Diagnosis of Drug Allergy are not Affected by a Topical Anesthetic Patch

The use of topical anesthesia to perform intradermal tests (IDTs) for drug allergy diagnosis was never investigated. We aimed to determine the effects of a topical anesthetic patch containing prilocaine-lidocaine on wheal size of IDT with drugs. Patients who had positive IDT as part of their investigation process of suspected drug hypersensitivity were selected. IDT were performed according to guidelines. Anesthetic patch (AP) was placed and the same prior positive IDT, as well as positive histamine skin prick test (SPT) and negative (saline IDT) controls, were performed in the anesthetized area. Patients with negative IDT were also included to check for false positives with AP. Increase in wheals after 20 minutes both with and without AP was recorded and compared. 45 IDT were performed (36 patients), of which 37 have been previously positive (14 antibiotics, 10 general anesthetics, 6 non-steroidal anti-inflammatory drugs, 3 iodinated contrasts, 3 anti-Hi-histamines and 1 ranitidine). Mean histamine SPT size without the AP was 4.7 mm [95%CI (4.4-5.1]), and 4.6 mm [95%CI(4.2-5.0)] with anesthesia. Mean wheal increase in IDT for drugs without the anesthesia was 4.5 mm [95%CI(3.3-5.7)] and with anesthesia was 4.3 mm [95%CI(2.8-5.8)]. No statistical significant differences were observed between skin tests with or without AP for histamine SPT (P=0.089), IDT with saline (P=0.750), and IDT with drugs (P=0.995). None of the patients with negative IDT showed positivity with the AP, or vice-versa. The use of an AP containing prilocaine-lidocaine does not interfere with IDT to diagnose drug allergy, and no false positive tests were found.     

Diagnosis and Immunotherapy of Mould Allergy

In order to screen for mould allergy, extracts of five common atmospheric moulds (Cladosporium, Alternaria, Penicillium, Aspergillus and Mucor) from various manufacturers were investigated in 130 patients (5-60 years old) with clinical symptoms indicating possible mould allergy. The patients were screened by skin prick test (SPT) and radioallergosorbent test (RAST). SPT seemed to be more sensitive than RAST as a diagnostic screening procedure (80% positive reactions to one or more species compared to 50%). With a partially purified, standardized preparation of Cladosporium herbarum more positive reactions were obtained than with crude extracts without evidence of any unspecific reactions. The difference between commercial and standardized extracts is most probably a result of a variation of both the biological potency of allergenic determinants and the allergenic composition. A considerable number of negative RAST reactions with standard discs were found in patients with positive skin reactions to partially purified Cladosporium, but RAST seemed to be more sensitive than SPT with the other commercial mould extracts. Based on the screening, a very convincing tendency to IgE-reactivity to other moulds was found in patients reacting to Cladosporium, the most common cause of mould allergy. The results confirm the inadequacy of most mould extracts used in diagnostic procedures and strengthen the value of using standardized extracts.     

Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group

When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical spectrum, and appropriate diagnostic methods particularly in children. Meanwhile, the tools used for DH management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of DH and management differ with age. Most reactions in children are still attributed to betalactams. Some manifestations, such as nonsteroidal anti‐inflammatory drug‐associated angioedema and serum sickness‐like reactions, are more frequent among young patients as compared to adults. Risk factors such as viral infections are particularly frequent in children, making the diagnosis challenging. The practicability and validity of skin test and other diagnostic procedures need further assessment in children. This study presents an up‐to‐date review on epidemiology, clinical spectrum, diagnostic tools, and current management of DH in children. A new general algorithm for the study of these reactions in children is proposed. Data are presented focusing on reported differences between pediatric and adult patients, also identifying unmet needs to be addressed in further research.     

A Complex Interaction Between Drug Allergy and Viral Infection

A relationship between viral infections and the simultaneous or subsequent development of drug rashes has been observed in a number of clinical situations. We have recently provided evidence to indicate an intimate relationship between reactivation of human herpesvirus 6 (HHV-6) and the development of a severe systemic hypersensitivity reaction referred to as drug-induced hypersensitivity syndrome (DIHS). This syndrome has several unique features that cannot be explained by a drug etiology; they include its delayed onset, paradoxical worsening of clinical symptoms after discontinuation of the causative drugs, and a step-wise development of several organ system failures long after clinical resolution. Many aspects of this syndrome suggest close similarities between DIHS and graft-versus-host disease (GVHD). Indeed, a wide variety of complications frequently occurring in GVHD, such as autoimmune diseases, is often observed during the course of this syndrome and even long after clinical resolution. Our recent studies have shown that in DIHS sequential reactivations of several herpesviruses (HHV-6, HHV-7, Epstein-Barr virus, and cytomegalovirus) can be detected coincident with various clinical symptoms in the same order as demonstrated in GVHD. Thus, not only the timing but also the order in which these herpesviruses can be reactivated in the host would be crucial determinant of outcomes of the disease. Our results indicate the importance of recognizing DIHS and other drug rashes associated with viral infections at risk of eventually developing autoimmune diseases.     

Diagnosis and Immunotherapy of Mould Allergy

To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group position paper

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.     

Allergy to foods in patients monosensitized to Artemisia pollen

It is known that patients with pollinosis may display clinical characteristics caused by allergy to certain fruits and vegetables, but subjects allergic to Artemisia seem to show particularly peculiar characteristics. The clinical features of 84 patients with rhinitis, asthma, urticaria, and/or anaphylaxis whose inhalant allergy was exclusively to Artemisia vulgaris were studied and compared with a control group of 50 patients monosensitized to grass pollen. The mean age for the beginning of symptoms was 30.2 years, and this was higher than in the control group ( P <0.05). We found the main incidence to be in women (70.2%). Some 42.3% had family history of atopia, lower than in the control group ( P <0.05), while the prevalence of asthma and urticaria was significantly higher ( P <0.05). Food hypersensitivity was reported by 23 patients (27.3%) allergic to Artemisia. The foods responsible (with respective numbers of cases) were honey (14), sunflower seeds (11), camomile (four), pistachio (three), hazelnut (two), lettuce (two), pollen (two), beer (two), almond (one), peanut (one), other nuts (one), carrot (one), and apple (one). None of the patients monosensitized to grass had food allergy. CAP inhibition experiments were carried out on a single patient. Results showed the existence of common antigenic epitopes in pistachio and Artemisia pollen for this patient. We concluded that mugwort hay fever can be associated with the Compositae family of foods, but that it is not normally associated with other foods.     

Prevalence of Immediate-Type Food Allergy in Early Childhood in Seoul

Purpose

There are scanty epidemiologic data on the prevalence of food allergy (FA) among preschool children in Asia. We performed this study to determine the prevalence and causative foods of immediate-type FA in early childhood in Korea.

Methods

A questionnaire-based, cross-sectional study was performed between September and October 2011. Children aged 0-6 years were recruited from 301 public child care centers in Seoul. Parents were asked to complete a questionnaire on FA. Children with FA were classified into "perceived FA, ever," "immediate-type FA, ever," and "immediate-type FA, current" according to the algorithm.

Results

A total of 16,749 children were included in this study. The prevalence of "perceived FA, ever," "immediate-type FA, ever," and "immediate-type FA, current" was 15.1%, 7.0%, and 3.7%, respectively. "Immediate-type FA, current" was reported by 182 (4.9%) out of 3,738 children aged ≤2 years, 262 (3.4%) of 7,648 children aged 3-4 years, and 177 (3.3%) of 5,363 children aged 5-6 years. Hen''s egg (126/621) was the most frequent cause as the individual food item, followed by cow''s milk (82/621) and peanut (58/621). Among the food groups, fruits (114/621), tree nuts (90/621) and crustaceans (85/621) were the most common offending foods. The three leading causes of food-induced anaphylaxis were hen''s egg (22/47), cow''s milk (15/47), and peanut (14/47).

Conclusions

The prevalence of immediate-type FA in early childhood is 3.7%, and is higher in younger children. The most common offending foods differed with age.