Search

The relation of gastrointestinal (GI) complaints to IgE-mediated allergy is not well understood. Increased numbers of “IgE-armed” mast cells have been observed in duodenal mucosa of patients with functional GI complaints. To explore whether total IgE and atopic sensitization were associated with functional GI complaints. Levels of serum total and specific IgE and GI complaints were measured in 161 patients and in a general population sample of 478 persons. Standard inhalant allergens were measured in the patient group, and selected inhalant allergens in the general population. GI complaints were assessed by two standardized questionnaires. The associations between GI complaints and total IgE were analyzed in multiple regression models. GI complaints were positively associated with higher total IgE levels (all: b = 0.028, p = 0.012; patient group: b = 0.038, p = 0.072; general population: b = 0.038, p = 0.005), but negatively associated with atopic sensitization (all: b = −11.256, p = 0.181; patient group: b = −85.667, p

Background As a strong inducer of IgE-antibodies to substituted ammonium ion epitopes (QAI), pholcodine (PHO) is a postulated cause of allergic anaphylaxis to neuromuscular blocking agents (NMBAs). Three years after withdrawal of PHO in Norway, a significant reduction in IgE-sensitization and anaphylaxis reporting was seen. Objective Six year follow-up study on the effects of PHO withdrawal on IgE-sensitization and anaphylaxis reporting. Methods From 650 acute consecutive reports (2005-2013) to the Norwegian Network for Anaphylaxis under Anaesthesia (NARA), total number of reports on suspected anaphylactic reactions, number of reactions where NMBAs were administered, number of reactions where serum IgE-antibodies (≥0.35 kUA/L) to suxamethonium (SUX) and PHO were present at time of reaction and anaphylaxis severity grades were retrieved. In addition, NMBA sales and prevalence of IgE-sensitization to PHO and SUX among “allergics” were monitored. Results From baseline period P0 (PHO on the market) through the first (P1) and second (P2) three year periods after withdrawal, significant falls in total reports (p

The reports on fish parasite Anisakis simplex allergy have increased in countries with high fish consumption in the last decade. In Norway, a high consumption country, the prevalence of immunoglobulin E (IgE) sensitization to A. simplex was still unknown. Thus, our objective was to investigate the sensitization prevalence in this country. At the Haukeland University Hospital, Bergen, Norway, two main groups of surplus serum samples were collected: one from newly recruited blood donors (BDO) and the other from the Allergy laboratory (ALL) after analysing IgE and IgE antibodies. The latter was divided into three series: one containing unsorted sera and two sorted by either Phadiatop � ‡0.35 kUA ⁄l or total IgE ‡1000 kU ⁄l. The sera were analysed for total IgE and IgE antibodies against A. simplex, shrimp, house dust mite (HDM), cod and cross-reactive carbohydrates (CCDs). The prevalence of IgE sensitization to A. simplex was 2.0%, 2.2% and 6.6% in BDO, the unsorted and Phadiatop � positive serum groups, respectively. A considerable degree of cross-sensitization to shrimp and HDM is further suggested. Unspecific binding because of high total IgE or by binding to CCDs seemed to play a minor role. The prevalence of IgE sensitization to A. simplex appears to be lower in a Norwegian population than in other high fish-consuming countries, but might still be overestimated owing to cross-sensitization.

The Scandinavian data on pholcodine (PHO) strongly indicates that there is a biological chain from PHO exposure through IgE-sensitization to IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBA). PHO is probably one of the strongest inducer of an IgE antibody response known. Of individuals taking PHO in cough medicines, over-the-counter accessibility to large populations, as many as 20 to 25% may become IgE sensitized. Once sensitized, PHO re-exposure will booster IgE antibody levels and IgE by around 100-fold. PHO is monovalent for 2 non-cross-reacting epitopes the quaternary ammonium ion (QAI), the main allergenic epitope of NMBA, and a non-QAI epitope. Thus, PHO most unlikely would initiate an allergic inflammatory response. Consequently, IgE sensitization is not revealed by obvious clinical signs, neither through tests based on IgE-sensitized effector cells. Therefore, it will escape detection if not assayed serologically. However, when subjected to general anesthesia, and thus the IgE-sensitized individual is administered a bivalent NMBA intravenously, the unrecognized presence of serum IgE antibodies to QAI may increase the risk of anaphylaxis 200- to 300-fold. Severe damages to patient's health can result, and mortality rates of 3 to 10% are reported. The Scandinavian experience indicates that the chain of events can efficiently be avoided by stopping PHO exposure: Within 1 year, the prevalence of IgE sensitization to PHO and QAI decreases significantly, and after 2 to 3 years, the numbers of reported anaphylactic reactions decreases equally so. Keywords: Over-the-counter cough medicines, IgE antibodies, pholcodine, anaphylaxis

Perceived food hypersensitivity is a prevalent, but poorly understood condition. In this review article, we summarize narratively recent literature including results of our 10 years' interdisciplinary research program dealing with such patients. The patients (more than 400) included in our studies were all adults referred to a university hospital because of gastrointestinal complaints self-attributed to food hypersensitivity. Despite extensive examinations, food allergy was seldom diagnosed. The majority of the patients fulfilled the diagnostic criteria for irritable bowel syndrome. In addition, most suffered from several extra-intestinal health complaints and had considerably impaired quality of life. However, psychological factors could explain only approximately 10% of the variance in the patients' symptom severity and 90% of the variance thus remained unexplained. Intolerance to low-digestible carbohydrates was a common problem and abdominal symptoms were replicated by carbohydrate ingestion. A considerable number of patients showed evidence of immune activation by analyses of B-cell activating factor, dendritic cells and "IgE-armed" mast cells. Multiple factors such as immune activation, disturbed intestinal fermentation, enteric dysmotility, post-infectious changes and "local" allergy in the gut as well as psychological disturbances may play a role in the pathophysiology of perceived food hypersensitivity. Hence, our results support the view that management of these patients should be interdisciplinary.

Background: IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBA), frequent in Norway, was proposed to be caused by exposure to pholcodine (PHO) carrying the allergenic quarternary ammonium ion epitope. Consequently, the PHO-containing drug was withdrawn from the market in March 2007. Objective: Describe the effects of withdrawal of PHO on IgE, IgE-antibodies and reported frequencies of anaphylaxis to NMBAs. Methods: Three hundred sera from supposedly allergic patients sampled yearly through 2006 to 2010 were analysed for IgE antibodies to PHO, suxamethonium (SUX) and morphine (MOR). Furthermore, IgE and preliminary reports from the Norwegian Network for Anaphylaxis under Anaesthesia (NARA) were monitored. Results: PHO exposure was associated with IgE sensitization to PHO, MOR and SUX. However, after withdrawal, within 1 year, antibody prevalences to PHO and SUX fell significantly from 11.0% to 5.0% and from 3.7% to 0.7%, respectively. At 3 years, SUX had fallen to 0.3%, PHO to 2.7% and MOR to 1.3%. By 2 years, the prevalence of elevated IgE was significantly reduced. After 3 years, the incidence of reported suspected anaesthetic anaphylaxis fell significantly, both the total number, the reactions related to NMBAs and those with IgE antibodies to SUX. Conclusions: Withdrawing of PHO lowered significantly within 1–2 years levels of IgE and IgE antibodies to PHO, MOR and SUX, and, within 3 years, the frequency of NMBA suspected anaphylaxis. The results strengthen the PHO hypothesis considerably and equally the need to question the existence of cough depressants containing PHO.

Background: Local anaesthetics (LA) are generally considered safe with respect to allergy. However, various clinical reactions steadily occur. Even though most reactions are manifestations of reflexes to perceptive stimuli, uncertainty often remains regarding a possible allergic mechanism. This uncertainty later leads to an avoidance of local anaesthesia and unnecessarily painful interventions, resource-consuming general anaesthesia or even the risk of re-exposure to other yet unidentified allergens. In the present study, follow-up procedures at an allergy clinic were analysed to examine the frequency of identified causative agents and pathogenetic mechanisms and evaluate the strength of the diagnostic conclusions. Method: The medical records of 135 cases with alleged allergic reactions to LA were reviewed. Diagnoses were based on case histories, skin tests, subcutaneous challenge tests and in vitro IgE analyses. Results: Two events (1.5%) were diagnosed as hypersensitivity to LA, articaine‐adrenaline and tetracaine‐adrenaline, respectively. Ten reactions (7%) were diagnosed as IgE-mediated allergy to other substances including chlorhexidine, latex, triamcinolone and possibly hexaminolevulinate. As challenge testing was not consistently performed with the culprit LA compound, follow-ups were short of definitely refuting hypersensitivity in 61% of the cases. The reported clinical manifestations were in general diagnostically unspecific, but itch and generalised urticaria were most frequent in test-positive cases. Conclusion: Reactions during local anaesthesia are rarely found to be an IgE-mediated LA allergy. Whenever the clinical picture is compatible with allergy, other allergens should also be tested.

BACKGROUND Anaphylaxis is a serious life-threatening generalized or systemic hypersensitivity reaction. The aim of this paper is to provide knowledge on how to diagnose, treat and follow up patients with suspected anaphylaxis during general and local anaesthesia. MATERIAL AND METHODS The article is based on literature identified through a non-systematic search in PubMed, the Scandinavian Guidelines on anaphylaxis during anaesthesia and on own research. RESULTS Anaphylactic symptoms during anaesthesia vary with respect to severity. Manifestations from skin and the cardiovascular and respiratory systems are present simultaneously in approximately 70 % of patients. Early treatment with adrenaline, fluid and extra oxygen may be vital for survival without sequelae. The following patients should be assessed before anaesthesia: those with moderate or serious reactions or with reactions that raise suspicion of allergy which may cause problems in connection with future treatment. Neuromuscular blocking agents are the main cause of IgE-mediated anaphylaxis during anaesthesia in Norway. New research has shown that allergy towards neuromuscular blocking agents can develop after ingestion of cough syrup containing pholcodine (stimulates asymptomatic production of antibodies). These antibodies cause cross-sensibilisation with neuromuscular blocking agents. The cough syrup Tuxi was withdrawn from the Norwegian market during spring 2007. INTERPRETATION Allergic reactions during anaesthesia are rare and potentially life-threatening; patients should be followed up and treated in a standardized way.

To cite this article: Johansson SGO, Florvaag E, Oman H, Poulsen LK, Mertes PM, Harper NJN, Garvey LH, Gerth van Wijk R, Metso T, Irgens A, Dybendal T, Halsey J, Seneviratne SL, Guttormsen AB. National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study. Allergy 2010; 65: 498–502. Abstract Background: The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased. Methods: National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P-aminophenyl-phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop® test (>0.35 kUA/l), collected in nine countries representing high and low PHO-consuming nations. Results: There was a significant positive association between PHO consumption and prevalences of IgE-sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO-containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE-sensitization. Conclusion: This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE-sensitization towards NMBAs.

Symptoms, signs, perceptions, and objective measures were studied in university buildings. Two problem buildings with a history of dampness and complaints were compared with two control buildings. Health investigations among university staff were performed at the workplace (n = 173) including tear film stability [non-invasive break-up time (NIBUT) and self-reported break-up time (SBUT)], nasal patency (acoustic rhinometry), nasal lavage fluid analysis [NAL: eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin] and atopy by total serum IgE and IgE antibodies (Phadiatop). Exposure assessment included inspections, thermal and atmospheric climate at 56 points modelled for all work sites. Multiple regressions were applied, controlling for age and gender. Exposure differences between problem buildings and controls were small, and variations between rooms were greater. Workers in the problem buildings had more general and dermal symptoms, but not more objective signs than the others. Adjusted day NIBUT and SBUT increased at higher night air temperatures, with B (95% CI) 0.6 (0.04-1.2) and 1.3 (-0.02 to 2.5), respectively. Higher relative humidity at mean day air temperature22.1 degrees C was associated with adjusted NIBUT and SBUT, with B (95% CI) 0.16 (0.03-0.29) and 0.37 (-0.01 to 0.75), respectively. Air velocity below recommended winter values and reduced relative humidity in the range of 15-30% were associated with dry air and too low temperature.Thermal climate in university buildings may be associated with both perceptions and physiological signs. Reduced night time air temperature, increased difference in air temperature between day and night, and fast changes in air temperature might impair indoor environment. This may have implication for energy-saving policies. It might be difficult to identify the exposure behind, and find the reason why, some buildings are defined as 'problem buildings'.

Background: Neuromuscular blocking agents (NMBAs) can cause anaphylaxis through immunoglobulin E (IgE) antibodies that bind quaternary ammonium ion epitopes. These epitopes are present in numerous common chemicals and drugs, exposure to which, theoretically, could be of importance in the development and maintenance of the IgE sensitization promoting allergic reactions. Pholcodine is one such drug, which in a recent pilot study was shown to induce a remarkable increase in serum IgE levels in two IgE-sensitized individuals. The present study explores the effect of pholcodine exposure on IgE in a population with previously diagnosed IgE-mediated anaphylaxis towards NMBAs. Methods: Seventeen patients were randomized to 1 week’s exposure with cough syrup containing either pholcodine or guaifenesin. The primary variables serum IgE and IgE antibodies towards pholcodine, morphine and suxamethonium were measured before and 4 and 8 weeks after start of exposure. Results: Patients exposed to pholcodine had a sharp rise in levels of IgE antibodies towards pholcodine, morphine and suxamethonium, the median proportional increases 4 weeks after exposure reaching 39.0, 38.6 and 93.0 times that of the base levels respectively. Median proportional increase of IgE was 19.0. No changes were observed in the guaifenesin group. Conclusion: Serum levels of IgE antibodies associated with allergy towards NMBAs increase significantly in sensitized patients after exposure to cough syrup containing pholcodine. Availability of pholcodine should be restricted by medical authorities because of the potential risk of future allergic reactions to muscle relaxants.

Aims: Rhinitis symptoms frequently occur in bakery-workers. Yet, little is known about the pathophysiology of this condition. The objective of the present study was to examine nasal indices of inflammation in relation to occupational dust exposure, occupational rhinitis according to defined criteria, rhinitis symptoms associated to the workplace, and occupational sensitization in bakery-workers. Methods: Bakery-workers (n = 197) were subjected to interviews, questionnaires, workplace dust measurements, allergy tests, and nasal lavages with and without histamine. alpha(2)-Macroglobulin and eosinophil cationic protein (ECP) were measured in saline lavages as indices of plasma exudation and eosinophilic activity, respectively. Histamine lavages were employed to explore the nasal exudative responsiveness. Results: alpha(2)-Macroglobulin and ECP increased significantly by increased workplace dust exposure (P

Background: A previous study showed a relation between pholcodine (PHO) consumption, prevalence of IgE-sensitization to PHO, morphine (MOR) and suxamethonium (SUX) and anaphylaxis to neuromuscular blocking agents (NMBA). The purpose of this pilot study was to explore the effect on IgE production, in IgE-sensitized and nonsensitized individuals, of exposure to cough syrup and environmental chemicals containing PHO, MOR and SUX related allergenic structures. Methods: Serum concentrations of IgE and IgE antibodies to PHO, MOR and SUX allergens measured by ImmunoCAPTM (Pharmacia Diagnostics, Uppsala, Sweden) were followed after intake of cough syrup, or exposure to confectionary and other household chemicals containing various amounts of substances cross-reacting with PHO, MOR and SUX. Results: Cough syrup containing PHO gave, in sensitized individuals, within 1–2 weeks, an increase of IgE of 60–105 times and of IgE antibodies to PHO, MOR and SUX in the order of 30–80 times. The tested confectionary did not have any similar stimulating effect but seemed to counteract the expected decrease of IgE. No effect was seen in nonsensitized individuals. The PHO stimulated IgE showed a nonspecific binding to ImmunoCAP with common allergens and glycine background ImmunoCAP that was up to 10-fold higher than that of monomeric myeloma-IgE at twice the concentration. Conclusions: It seems as cough syrups containing PHO have a most remarkable IgE boostering effect in persons IgE-sensitized to PHO, MOR and SUX related allergens. Household chemicals containing such allergenic epitopes seem capable of some, minor, stimulation.

Background: Abdominal complaints related to food intake might be due to hypersensitivity. A firm diagnosis of food allergy is often difficult to establish, particularly in the absence of systemic food-specific IgE. Using ultrasonography and magnetic resonance imaging (MRI) we were able to visualise the intestinal response in one such case. Methods: A 24-year-old female presented with self-reported food hypersensitivity, particularly related to the intake of egg. Nausea and diarrhoea were predominant symptoms. Double-blind placebo-controlled food challenge with raw egg was positive, but all other conventional tests of food hypersensitivity, including skin prick test, total and food-specific IgE in serum, were negative. A thorough investigation programme could not reveal any organic disease of the gastrointestinal tract. We extended the evaluation to include two new provocation tests, where intestinal wall thickening and the amount of luminal liquid were monitored by external abdominal ultrasound and MRI. Results: Both ultrasound and MRI investigations indicated intestinal wall thickening and influx of large amounts of fluid into the proximal small intestines within 10 min of duodenal challenge with egg. The response was associated with abdominal pain and bloating. Conclusions: The response to provocation was typical of an immediate allergic reaction. Our results indicate that local food-induced hypersensitivity reactions can occur in the gut in the absence of systemic indications of IgE-mediated allergy. Abdominal ultrasonography and MRI might become valuable tools for documenting such responses.

Background Several studies have recognized neuromuscular blocking agents as the most common cause of anaphylaxis during general anesthesia, but the reported frequencies vary considerably between countries. In Norway, the issue has raised special concern because of reports from the Norwegian Medicines Agency that suggest a high prevalence. This article presents the results from a standardized allergy follow-up examination of 83 anaphylactic reactions related to general anesthesia performed at one allergy center in Bergen, Norway. Methods Eighty-three cases were examined during the 6-yr period of 1996-2001. The diagnostic protocol consisted of case history, serum tryptase measurements, specific immunoassays, and skin tests. Results Immunoglobulin E-mediated anaphylaxis was established in 71.1% of the cases, and neuromuscular blocking agents were by far the most frequent allergen (93.2%). Suxamethonium was the most frequently involved substance, followed by rocuronium and vecuronium. The few reactions in which other allergies could be detected were mainly linked to latex (3.6%). Conclusions Neuromuscular blocking agents were the dominating antigens causing immunoglobulin E-mediated anaphylaxis in this study. The data could not be used for estimation of the incidence of allergy toward neuromuscular blocking agents in Norway. Larger patient samples, standardization of reporting, and diagnostic protocols should be pursued by network formation to produce data more suitable for epidemiologic research.

Owing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be recognized by ultrasound.Thirty-two patients with chronic abdominal complaints, self-attributed to food hypersensitivity/allergy were included in the study. Via a nasoduodenal tube, the duodenal mucosa was challenged with the suspected food item dissolved in 10 ml water or saline. Using external ultrasound, the sonographic features (wall thickness and diameter of the duodenal bulb and jejunum, peristalsis activity and luminal fluid) were recorded before and during one hour after challenge.Sonographic changes were observed after challenge in 14 (44%) of the 32 patients. A positive sonographic response (increased wall thickness, diameter, peristalsis and/or luminal fluid) was significantly related to a positive skin prick test (p = 0.008) and a positive double-blind placebo-controlled food challenge (p = 0.03). A significant correlation was found between provocation-induced symptoms and wall thickness of the duodenal bulb (r = 0.50, p = 0.004) or the jejunum (r = 0.42, p = 0.02). Intra- and interobserver variation of the tracing procedure showed low values.Responses of the proximal small intestines to direct provocation (swelling of the wall and exudation of fluid into the lumen) could be visualized by transabdominal ultrasound. This new provocation test could be helpful in the evaluation of patients with food hypersensitivity.

The aim of this study was to investigate quality of life and applicability of the 10-item short form of the Nepean Dyspepsia Index (SF-NDI) in patients with subjective food hypersensitivity. Fifty-two adult patients and 120 controls were examined using three questionnaires: Quality of life Nepean Dyspepsia Index (NDI), Gastrointestinal Symptom Rating Scale (GSRS), and Ulcer Esophagitis Subjective Symptoms Scale (UESS). To document psychometric properties, 20 of the patients filled in the SF-NDI questionnaire once more 4 weeks later. Patients had poor quality of life compared with controls from health care workers or general population (P < 0.001). Scores on SF-NDI were significantly correlated with scores on the GSRS (r = 0.34, P = 0.02) and UESS (r = 0.41, P = 0.003). The SF-NDI performed very satisfactorily, with a high reliability, construct validity, and responsiveness. Patients with subjective food hypersensitivity have considerably reduced quality of life. The SF-NDI provides reliable, responsive, and clinically valid measures of quality of life in these patients.

Background: In the perioperative setting multiple agents can cause anaphylaxis. Often the reactions are dramatic, and due to their lifethreatening potential it is crucial that the responsible agent is identified in order to avoid future adverse reactions. The aim of the present study was to measure the concentration of serum mast cell tryptase (MCT), to investigate the prevalence of serum IgE antibodies against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex and to perform skin prick tests (SPTs) in 18 patients experiencing an anaphylactic reaction during induction of general anaesthesia. Methods: Serum samples from 18 patients with an anaphylactic reaction during general anaesthesia were analyzed for MCT and specific IgE against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex. Skin prick tests were performed in 11 out of 18 patients. Results: Ten patients had elevated MCT levels and specific IgE against ammonium ion, morphine and (with the exception of patient nos 3, 9 and 10) suxamethonium. Seven of these patients had positive SPTs to suxamethonium. One of the patients tested positive to latex in addition to suxamethonium. Two patients showed elevated MCT, while specific IgE against the drugs tested was not detected. Three patients tested positive to ammonium ion, morphine and suxamethonium, but negative to MCT. Three patients tested negative to both MCT and specific IgE. Conclusions: Fifteen out of 18 sera tested positive for MCT and/or specific IgE against neuromuscular blocking drugs (NMBDs). Ten of the 18 patients experienced an IgE-mediated anaphylactic reaction to NMBDs during anaesthesia, verified by detection of specific IgE and elevated levels of MCT.

We examined changes in the self-reported prevalence of respiratory symptoms and total serum immunoglobulin E (IgE) among hairdressers after local exhaust ventilation was installed in some hairdresser salons. We also examined differences in these variables between current and former hairdressers. The survey was a prospective study on 91 female hairdressers and a control group of 80 female office workers. Total serum IgE remained high in the hairdresser groups both in 1995 and 1999 (101 vs. 105 IU/mL blood). The IgE levels among office workers were low in 1995 and 1999. Forty percent of the hairdressers in 1995 had left their profession by 1999, 5.7 times the rate among office workers. The frequency of wheezing in the past year decreased significantly among current and former hairdressers. Our data suggest that hairdressers who remained in their profession were a highly selected and healthy group of workers. The improvement in symptoms might be explained by the reduced exposure resulting from the installation of local exhaust ventilation.

Background: Muscle relaxants are believed to be responsible for 2/3 of the cases of anaphylactic reactions during anesthesia. This assumption is based mainly on positive skin tests obtained in individuals that have experienced anesthesia-related anaphylaxis. A positive skin test is supposed to be associated with mast cell degranulation of vasoactive amines. In the present study we tested the frequency of positive skin tests with two commonly used muscle relaxants, rocuronium and cisatracurium, in a selected group of volunteers with low potential for allergic reactions. Methods: Thirty healthy volunteers without known allergy or previous exposure to muscle relaxants were studied. Low potential for allergic reactions was determined prior to inclusion in the study, using various allergy tests. Each individual was tested with intradermal and skin prick tests, and molar drug concentration thresholds for positive skin reactions were determined using a dilution titration technique. The presence or absence of mast cell degranulation was tested by electron microscopic investigation of skin biopsies obtained from positive and negative skin reactions. Results: None of the volunteers had a positive skin prick test. More than 90% of the volunteers had a positive intradermal test with both rocuronium and cisatracurium. The highest molar drug concentration that was not associated with a positive intradermal test was 10−6 M (rocuronium) and 10−7 M (cisatracurium), equivalent to vial dilution 1 : 1000 for both drugs. In none of the volunteers was mast cell degranulation detected. Conclusion: Non-mast-cell-mediated positive intradermal skin reactions are frequently occurring with rocuronium and cisatracurium, even at vial dilution 1 : 1000. A clinically applicable test technique is needed that is able to separate positive skin tests associated with mast cell degranulation from non-mast-cell-mediated reactions.

Objectives This study assessed the effect of exposure to hairdressing chemicals on total and allergen-specific serum immunoglobulin E (IgE) in hairdressers. Methods The study was based on a questionnaire sent to 100 hairdressers (91% responding) and a reference group of 95 office workers (84% responding). The questionnaire sought information on allergy, respiratory symptoms during the past year, work conditions (exposure), and smoking habits. The hairdressers were divided into two groups, one of high exposure and another of low exposure. Total serum IgE and allergen-specific IgE towards the most prevalent airborne allergens were analyzed. Results The serum levels of total IgE were significantly higher among the highly exposed hairdressers than among the office workers. The prevalence of asthma-like respiratory symptoms during the past year was significantly higher among the highly exposed hairdressers than among the office workers. The total serum IgE level was significantly higher among the hairdressers than among the office workers (101 versus 51 IU/ml blood), but this difference disappeared after adjustment for age, atopy, and smoking. A total of 5.5% of the hairdressers versus none of the office workers had specific serum IgE antibodies towards latex. There were no differences in general allergy (Phadiatop(r)) among the hairdressers and office workers. Conclusions Serum levels of total IgE were significantly higher among highly exposed hairdressers than among office workers. The relationship could not be completely explained by such covariables as age, smoking, or sensitization to latex allergens.

Background: Latex allergy has become prevalent among health care workers. Objectives: To determine the prevalence of self-reported symptoms related to latex exposure among hospital personnel. Methods: Questionnaires addressing symptoms and risk factors for latex allergy were distributed to all employees (n = 5,087) at Haukeland University Hospital. Results: Symptoms associated with latex exposure were reported by 23.8% of the participants. Skin symptoms were most frequently reported – flushing/itching/hives: 21.0%, hand eczema: 11.8% – while systemic and respiratory symptoms were reported by 1.4 and 1.2%, respectively. Approximately twice as many women than men reported symptoms (odds ratio 2.55, confidence interval 2.04–3.18). Symptoms were reported by 33.7% of those with atopy and by 20.0% of those without. The occurrence of symptoms increased significantly with the frequency of use of latex gloves but was unrelated to age, years of exposure or number of surgical procedures. Conclusions: The occurrence of self-reported symptoms was associated with the frequent use of latex gloves, atopy and female gender.

Background Accumulating data indicates that pholcodine (PHO)-consuming countries have higher sero-prevalences of immunoglobulin E (IgE)-antibodies to PHO and suxamethonium (SUX) and increased frequencies of IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBAs) than nonconsuming. Withdrawing PHO-containing cough syrups resulted in a significant decrease of cases with anaphylaxis in Scandinavia. Nevertheless, the European Medicines Agency in 2011 advised to continue the unrestricted use throughout the European Union. Objective To extend studies on PHO consumption and prevalence of IgE-sensitization to morphine (MOR), PHO, and SUX to countries representing high (Australia), and low (Korea and Japan), consumers, respectively. Methods IgE-antibodies to SUX, MOR, and PHO in atopic subjects were determined by immunoassay and compared with official figures for PHO consumption and reported anaphylaxis to NMBA. Results The prevalences of IgE-antibodies to PHO, MOR, and SUX were 10%, 8.6%, and 4.3%, respectively, in Australia. The corresponding figures for Japan were 0.8%, 0.8%, and 1.5%, and for Korea 1.0% to PHO and 0.5% to MOR and SUX. Of the SUX-positive sera, 100% were positive to PHO or MOR in Australia and 0% in Japan and Korea. Conclusion The study supports previous findings; exposure to PHO may induce IgE-antibodies to the substituted ammonium ion epitope of NMBAs, thus increasing risk of NMBA-induced anaphylaxis considerably. However, other, still unknown factors occasionally might induce IgE-antibodies to SUX.

During the last decade, cases of the fish parasite Anisakis simplex infection and allergy in human have increased in countries with high fish consumption. Our aim was to perform an extended seroprevalence study of anti-IgE antibodies against this parasite in Norway, one of the high fish-consuming countries. At the Department of Immunology and Transfusion Medicine and the Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway, two main groups of anonymized serum samples were collected; the first (n = 993) from recently recruited blood donors (designated 'BDO') and the second (n = 414) from patient with total IgE levels ≥1000 kU/l (designated 'IGE+'). The sera were analysed by the ImmunoCAP(®) method for total IgE and IgE antibodies against A. simplex, house dust mite (HDM), shrimp, cod, crab, brine shrimp and shrimp tropomyosin. The A. simplex positive sera were further tested by an enzyme-linked immunosorbent assay (ELISA) method, which uses 2 recombinant (r) major allergens, rAni s 1 and rAni s 7 as target antigens. SDS-PAGE and Western immunoblotting analyses were also performed. Whereas the prevalences by ImmunoCAP(®) were 0.4% and 16.2% in the BDO and IGE+ groups, respectively, analyses with recombinant allergens showed only 0.0% and 0.2%. Cross-reactivity and immunoblotting analyses suggested that most of the ImmunoCAP(®) positive sera were probably false-positive due to cross-sensitization to shrimp and HDM. However, positivity due to other A. simplex antigens should also be considered. Compared with other high fish-consuming countries, we observed a very low seroprevalence of anti-Anisakis IgE antibodies in a Norwegian population.

Aliment Pharmacol Ther 31, 1112–1122 Summary Background An association between atopic disease and gastrointestinal complaints has been suggested. Aim To explore the association between atopic disease, gastrointestinal symptoms, and possible gastrointestinal manifestations of atopic disease in patients with self-reported food hypersensitivity. Methods Symptoms, skin prick tests, serum markers of allergy and intestinal permeability were recorded in 71 adult patients. Eosinophils, tryptase- and IgE-positive cells were counted in duodenal biopsies. Results Sixty-six (93%) patients had irritable bowel syndrome (IBS) and 43 (61%) had atopic disease, predominantly rhinoconjunctivitis. All 43 were sensitized to inhalant allergens, 29 (41%) to food allergens, but food challenges were negative. Serum total IgE and duodenal IgE-positive cell counts were significantly correlated (P

Background Artemia (brine shrimp) is used as feed for fish fry and shrimp in aquaculture. Two employees in a Norwegian aquaculture research farm reported having chest symptoms when working in an Artemia hatch room. Aims To determine the presence and prevalence of Artemia sensitization at the farm and the extent of any Artemia-related respiratory and hand skin symptoms and to identify the allergens involved. Methods Participants completed a questionnaire and structured interview. Skin prick tests (SPTs) were performed, and immunoglobulin E (IgE) antibodies to Artemia, shrimp and recombinant tropomyosin were determined. Gel electrophoresis and immunoblots of Artemia extracts were also carried out. Results Thirty of 42 employees (71%) participated. Among the 24 subjects exposed to Artemia, four (17%) reported chest and/or hand skin symptoms during exposure and three of them were IgE sensitized to Artemia. Five (21%) of those exposed demonstrated IgE antibodies to Artemia and four (17%) had immediate-positive SPTs. A serum pool from these subjects exhibited IgE binding to a protein of approximately 97 kDa in the Artemia extract. Conclusions Occupational exposure to the Artemia fish fry feed can cause IgE sensitization and allergic symptoms affecting airways and skin.

The present approach to the diagnosis, management and follow-up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia. The recommendations are based on the best available evidence in the literature, which, owing to the rare and unforeseeable nature of anaphylaxis, mainly includes case series and expert opinion (grade of evidence IV and V). These guidelines include an overview of the epidemiology of anaphylactic reactions during anaesthesia. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline (epinephrine) and fluid therapy as first-line treatment. Recommendations for primary and secondary follow-up are given, bearing in mind that there are variations in geography and resources in the different countries. A list of National Centres from which anaesthesiologists can seek advice concerning follow-up procedures is provided. In addition, an algorithm is included with advice on how to manage patients with previous suspected anaphylaxis during anaesthesia. Lastly, Appendix 2 provides an overview of the incidence, mechanisms and possibilities for follow-up for some common drug groups.

Background: Reactions after a blood transfusion could be allergic because of passive transfer of immunoglobulin E (IgE) antibodies from allergic donors. Aims of the study: To compare spectrum and prevalence of IgE antibodies in blood donors from Sweden and Norway. Methods: Using the ImmunoCAP method, serum samples from 1002 blood donors from Sweden and 500 from Norway were analysed for IgE antibodies to common inhalant and food allergens and allergens common in a hospital environment, such as penicilloyl G and latex. Results: As many as 23.6–27.3% of the donors had IgE antibodies to at least one of the 14 allergens tested. Of these 6.8–16.7% had extremely high concentrations, i.e. >35 kUA/l corresponding to 100 times the cut-off for a positive allergy test. Most donors were sensitized to pollens, dander and mite but several had very high levels of IgE antibodies to penicilloyl G, latex and peanut. The pattern of sensitizing allergens differed between Sweden and Norway. Conclusions: High serum levels of IgE antibodies to various allergens are common among blood donors and the degree of sensitization and spectrum of involved allergen varies between geographical regions. Present routines to identify IgE sensitized, potential risk, donors are not satisfactory; the sensitivity of selection procedures is about 25%.

Perceived food hypersensitivity is much more common than food allergy as medically verified. Unexplained symptoms and wrong attribution are typical in subjective health complaints. We hypothesize that subjective health complaints and worries are abnormally prevalent among patients with subjective food hypersensitivity. Forty-six patients with subjective food hypersensitivity and two control groups, one formed by 50 health care workers and one by 70 sex- and age-matched volunteers from the general population, were included in our study. All filled in two questionnaires: Subjective Health Complaints Inventory and Modern Health Worries Scale. None of the patients had IgE-mediated food allergy. The patients scored significantly higher than the controls on sum scores for four domains of subjective health complaints, including gastrointestinal complaints (P < 0.001), musculoskeletal complaints (P < 0.01), "pseudoneurology" (P < 0.001), and allergy (P < 0.001). Sum scores on modern health worries did not differ significantly between groups. The results support our hypothesis of an association between subjective food hypersensitivity and subjective health complaints, corroborating the view that, in the absence of food allergy, the conditions are sharing pathogenetic mechanisms.

Background: Anaphylactic reactions to a neuromuscular blocking agent (NMBA) is more than six times as common in Norway as in Sweden, probably due to differences in preoperative sensitization. The prevalence of IgE-sensitization to morphine (MOR) and suxamethonium (SUX) in comparable populations in Bergen, Norway, and Stockholm, Sweden, was studied and related to possible sensitizing agents. Methods: Three hundred sera of ‘allergics’ and 500 blood donors in Bergen and Stockholm were tested for IgE antibodies to MOR and SUX using Pharmacia Diagnostics ImmunoCAP 1 (Uppsala, Sweden) assay and the results compared to those of 65 patients from Bergen with documented anaphylaxis to NMBA. In addition, 84 different household chemicals were tested, by IgE antibody inhibition, for SUX and MOR. Results: In Norway 0.4% of blood donors, 3.7% of allergics and 38.5% of anaphylactics were IgE-sensitized to SUX, and 5.0, 10.0 and 66.7%, respectively, to MOR. No serum from Sweden was positive. The majority of those sensitized (69%) were women. Several household chemicals contained SUX and/or MOR activity, but the only difference between Norway and Sweden was cough mixtures containing pholcodine (PHO). IgE antibodies to PHO were present in 6.0% of blood donors from Norway and in no serum from Sweden. Of the anaphylactics, 65—68% were sensitized to MOR or PHO but only 39% to SUX. Conclusions: IgE-sensitization to SUX, MOR and PHO was detected in Norway but not in Sweden. One possible explanation is the unrestricted use of cough mixtures containing MOR derivatives in Norway.

Patients with food hypersensitivity suffer poor quality of life and several unexplained health complaints, both abdominal and extra-abdominal. Part of the suffering is due to healthcare providers' neglect and poor insight, allowing a strong position for alternative medicine. Distinguishing food allergy from functional and organic disorders can be extremely difficult. We have found examination of faecal calprotectin and gut permeability to be useful for excluding organic disease, whilst conventional provocation tests for positive diagnosis of food hypersensitivity are cumbersome. Our new ultrasound provocation test has been promising, but we acknowledge that much work remains to be done before its sensitivity and specificity can be finally established. The majority of patients with self-reported food hypersensitivity have a non-allergic hypersensitivity disorder. We suggest that cognitive-emotional sensitisation at the brain level, and not peripheral (immunological) sensitisation, is a major pathogenetic mechanism by which the patients' various abdominal and extra-abdominal health complaints are generated. Extensive activation of cognitive networks might be triggered by peripheral sensory mechanisms, often misinterpreted as 'food allergy'. Clearly, the approach to patients with food hypersensitivity should be interdisciplinary.

Background/Aim: Subjective food hypersensitivity is prevalent in the general population. The aim of this study was to seek objective evidence of food hypersensitivity by analyzing intestinal permeability and inflammation markers in gut lavage fluid. Methods: Fifty-two patients with abdominal complaints self-attributed to food hypersensitivity were examined by skin prick test, serum IgE analysis, double-blind, placebo-controlled food challenge (DBPCFC), and intestinal lavage. The results were compared with those of 44 patients without food hypersensitivity. Neither the patients nor the controls had organic diseases that could explain their symptoms. Intestinal lavage was performed by administering 2 liters of isotonic polyethylene glycol (molecular weight 3,350 daltons) solution containing 50 µCi of [51Cr]EDTA through a nasoduodenal tube. The first clear fluid passed per rectum was collected and analyzed for histamine, eosinophilic cationic protein (ECP), tryptase, and calprotectin. The intestinal permeability was assessed by determining the 5-hour urinary excretion of [51Cr]EDTA. Calprotectin was also analyzed in native faecal samples. Results: The ECP concentration in gut lavage fluid was significantly higher in the patients than in the controls (p = 0.007), but the overlap between groups was large. Food hypersensitivity was confirmed by positive DBPCFC in only 4 patients. On average, histamine and ECP concentrations were high in these patients. Tryptase, intestinal permeability, and faecal and lavage calprotectin levels were normal. Conclusions: Very few patients had objective evidence of food hypersensitivity. Analyzing intestinal permeability and inflammation markers in gut lavage fluid did not contribute to the diagnosis, but further studies on histamine and ECP are warranted.

Objective: Objective assessment of adverse reactions to food is a long-felt want. We report our preliminary experience with a new endosonographic allergen provocation test. Methods: Twenty patients were examined, seven patients having food allergy and 13 having food intolerance. The duodenal mucosa was challenged with allergen extracts via a nasoduodenal tube. The responses were recorded using a miniprobe for endosonography through the tube. Thereafter, intestinal lavage was performed by giving 2 l PEG solution containing 50 μCi 51 CrEDTA. The gut lavage fluid and urine for 5 h were collected. Results: Increased mucosal thickness in response to provocation was recorded in 11 patients, but not more often or pronounced in the allergic than in the intolerance group. Interestingly, increased mucosal thickness associated with a new echogenic layer was seen in two patients and a sustained duodenal contraction, lasting 15–20 min associated with pain, in another two. Intestinal permeability and inflammatory mediators were not significantly different in the two groups. Conclusion: In patients with self-reported adverse reactions to food abnormal responses to duodenal provocation may be recognised by endosonography. However, neither endosonography nor intestinal permeability or faecal calprotectin responses were able to distinguish between food allergy and intolerance. Sustained duodenal contractions in response to food might be a cause of abdominal pain.

OBJECTIVE—To assess respiratory symptoms among hairdressers in Norway. METHODS—The study was based on a questionnaire sent to 100 hairdressers (91% responding) and 95 office workers (84% responding). The questionnaire sought information about allergy, respiratory symptoms in the past year, and symptoms after exposures to different types of pollutants, working conditions, and smoking habits. A population based control group was established because the hairdressers and office workers differed in age and smoking habits. RESULTS—The prevalence of respiratory symptoms in the past year did not differ significantly between hairdressers and office workers after adjusting for age, atopy, and smoking. The hairdressers over 40 years of age reported significantly more symptoms—such as wheezing and breathlessness—in the past year than the office workers of the same age. Compared with the population based control group, both hairdressers younger than 30 and those over 40 reported more symptoms—such as breathlessness in the past year. The oldest hairdressers reported such symptoms as wheezing and breathlessness more often than did the younger hairdressers. These differences in breathlessness were significant after adjusting for smoking and wheezing. The same trend was not found among the office workers. The hairdressers reported significantly more wheezing, breathlessness, runny eyes, and blocked or runny nose from exposure to hair dyes, permanent oils, bleaching powder, and other chemicals used in a hairdressing salon, compared with the office workers. Prevalence of symptoms during exposure to other types of generel pollutants was similar in the two groups. CONCLUSIONS—Hairdressers are exposed to low levels of various irritating chemicals every day. The prevalences of acute symptoms related to the exposure of hairdressers to hairdressing chemicals are very high. Hairdressers, especially the oldest hairdressers, have more asthma-like symptoms than the control groups. Keywords: hairdresser; allergy; asthma

Background The present study investigated to what extent shrimp allergic individuals were IgE-sensitized to anisakis, crab and house dust mite and whether tropomyosin was responsible for IgE cross-reactivity. Methods 29 Individuals with self reported shrimp allergy were recruited by advertisements in local and national news-papers in Norway. Anamnesis was taken, skin prick tests (SPT) were performed and positive responders to shrimp were studied further with basophile activation test (BAT), ImmunoCAP analyses and western blotting. Results Of the 29 persons studied, 10 (34%) had positive SPT against shrimp and house dust mite, 9 (31%) against shrimp tropomyosin and 3 (10%) against anisakis. Individuals with positive SPT to shrimp all showed positive basophilic responses to house dust mite, while 43% responded to shrimp, 25% to anisakis and 36% to crab in BAT. Moreover, SPT, BAT as well as ImmunoCAP analyses showed a positive correlation of IgE-reactivity between anisakis and shrimp, house dust mite and crab. Immunoblot studies indicated that these responses are not completely explained by cross-reactivity towards tropomyosin. Conclusions The current study indicates a positive correlation between IgE-mediated reactions to shrimp, anisakis, house dust mite and crab, which may not be completely explained by cross-reactivity against tropomyosin.

Background Bronchial hyperresponsiveness (BHR) is common in bakery workers. The relation between bronchial responsiveness measured with a tidal breathing method and smoking, airway symptoms, IgE-sensitization, nasal indices of inflammation and flour dust exposure have been studied with bronchial responsiveness expressed as a continuous outcome. Material and methods Bakery workers (n = 197) were subjected to interviews, questionnaires, allergy tests, workplace dust measurements and bronchial metacholine provocation. Eosinophil cationic protein (ECP) and alpha(2)-macroglobulin were measured in nasal lavage. Bronchial responsiveness was expressed as slope(conc), a measurement based on regressing the per cent reduction in FEV1 at each provocation step. Results BHR expressed as slope(conc) was associated with smoking (P = 0.009), asthma symptoms at work (P = 0.001), and occupational IgE sensitization (P = 0.048). After adjusting for baseline lung function the association between BHR and IgE sensitization was no longer present. We demonstrated an association between nasal ECP and BHR (slope(conc) < 3: P = 0.012), but not to alpha(2)-macroglobulin in nasal lavage. No association was seen between BHR and current exposure level of flour dust, number of working years in a bakery or a history of dough-making. Conclusions BHR is related to baseline lung function, work-related asthma symptoms, smoking and nasal eosinophil activity, but not to occupational IgE sensitization and current flour dust exposure when measured with metacholine provocation. The slope(conc) expression seems to be a useful continuous outcome in bronchial responsiveness testing. (Less)

The use of different diagnostic criteria has considerable consequences for the prevalence estimates of occupational rhinitis. There is a strong relationship between occupational rhinitis and lower airway symptoms. Storage mites appear to be important occupational allergens in Norwegian bakeries.To study the consequences of various diagnostic criteria on the prevalence of occupational rhinitis, assess the prevalence of IgE sensitization and explore the relationships between upper and lower airway symptoms and between symptoms and IgE sensitization.A total of 197 employees in 6 bakeries were interviewed and completed a questionnaire. A skin prick test was performed, total and specific IgE were determined and a histamine release test was performed for relevant allergens. The criteria for the diagnosis of occupational rhinitis were based on the 1994 International Consensus Report on Rhinitis.The prevalence of occupational rhinitis varied between 23% and 50%, depending on the criteria used. The occurrence of nasal symptoms was found to precede the development of lower airway symptoms. Occupational rhinitis, both IgE- and non-IgE-mediated, was associated with asthma symptoms. The most frequent causes of sensitization (20%) were different species of storage mites. Storage mite sensitization was related to occupational rhinitis and work exposure.