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Background: Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error., Objective: To assess skin testing, quantification of specific IgE (sIgE) and flow-assisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy., Methods: This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests., Results: The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 92-99%), 97% (CI 95%: 88-100%) and 83% (CI 95%: 74-89%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 86-99%), 75% (CI 95%: 67-75%) and 72% (CI 95%: 58-83%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients., Conclusion: Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result. Optimal assessment of cross-reactivity between rocuronium and vecuronium implies both skin testing and BAT., (© 2011 John Wiley & Sons A/S.)

Correct management of anaphylaxis during anaesthesia requires a multidisciplinary approach with prompt recognition and treatment of the acute event by the attending anaesthesiologist, and subsequent determination of the responsible agent(s) with strict avoidance of subsequent administration of all incriminated and/or cross-reacting compounds. However, correct identification of the causative compound(s) and safe alternatives is not always straightforward and, too often, not done. This review is not intended to discuss acute management of anaesthesia-related anaphylaxis but summarizes the major causes of anaphylaxis during anaesthesia and the diagnostic approach of this rare but potentially life-threatening complication. Apart from general principles about the diagnostic approach, history taking and importance of tryptase quantification, more specific confirmatory diagnostic procedures are organized on the basis of the major causes of perioperative anaphylactic reactions.

Physicians predominantly rely upon quantification of serum-specific immunoglobulin E (IgE) and/or skin test to confirm clinically suspected IgE-mediated allergy. However, for various reasons, identification of the offending allergen(s) and potentially cross-reactive structures is not always straightforward. Flow-assisted allergy diagnosis relies upon quantification of alterations in the expression of particular basophilic activation markers. Actually, upon challenge with a specific allergen, basophils not only secrete quantifiable bioactive mediators but also upregulate the expression of different markers which can be detected efficiently by flow cytometry using specific monoclonal antibodies. Currently, the technique has been applied in the investigation of IgE-mediated allergy caused by classical inhalant allergens, food, Hevea latex, hymenoptera venoms and drugs. It is also appreciated; the technique proves valuable in the diagnosis of non-IgE-mediated (anaphylactoid) reactions such drug hypersensitivity and the detection of autoantibodies in certain forms of chronic urticaria. This review will not address immunologic features, characteristics and general pitfalls of flow-assisted analysis of in vitro-activated basophils as summarized elsewhere. After a recapitulation of the principles and some specific technical issues of flow-assisted analysis of in vitro-activated basophils, we principally focus on the current clinical and research applications of the basophil activation tests. Personal experience of both research groups is provided, where appropriate. Finally, a viewpoint on how the field might evolve in the following years is provided.

Background: Diagnosis of anaphylaxis from neuromuscular blocking agents (NMBA) is not always straightforward., Objectives: To assess flow cytometric analysis of activated basophils (BAT) as a diagnostic instrument in anaphylaxis from rocuronium. To investigate whether the technique might help to identify cross-reactive and safe alternative compounds., Methods: For validation of the BAT, 14 patients with perioperative anaphylaxis demonstrating a positive skin test (ST) for rocuronium and eight individuals that tolerated rocuronium and a negative ST for this drug were enrolled. To confirm specificity of the BAT, five patients that tolerated atracurium or cisatracurium with a negative ST for rocuronium were tested. Basophil activation with rocuronium, vecuronium, atracurium, cisatracurium and suxamethonium was analysed flow cytometrically by labelling with anti-CD123/anti-HLADR/anti-CD63., Results: Sensitivity of BAT for rocuronium was 91.7% and specificity 100%. However, in two patients the BAT was lost as a diagnostic tool, as their cells were nonresponsive to positive control stimulation and allergen. Seven from the 12 responsive patients also demonstrated a clear basophilic activation for vecuronium. Moreover, according to ST and/or BAT cross-reactivity between rocuronium and vecuronium was suspected in 10/14 patients. Except one patient, all patients had negative BAT and ST investigations for atracurium and cisatracurium. Currently, five patients tolerated administration of cisatracurium. All control individuals demonstrated negative ST and BAT for all tested NMBA., Conclusions: The BAT constitutes a reliable instrument to diagnose anaphylaxis from rocuronium. The technique also allows quick and simultaneous testing of different potential cross-reactive NMBA and to tailor a safe alternative.

Anaphylactic and anaphylactoid reactions related to haemodialysis have been increasingly described for almost 3 decades. The majority of these cases used to occur with ethylene oxide sterilized, and complement-activating cellulose membranes. However, a considerable number of publications have focused on polyacrylonitrile AN69 high flux membranes, angiotensin converting enzyme inhibitors and iron as other important causes of potentially severe haemodialysis-related anaphylactoid reactions. Clinical manifestations vary considerably and generally do not allow differentiation between IgE-mediated anaphylaxis and anaphylactoid reactions (e.g. from nonspecific mediator release). Successful management of these patients requires multidisciplinary approach and involves prompt recognition and treatment by the attending physician, and identification of the offending agent(s) with subsequent avoidance of the incriminated compound(s). This review focuses on some major causes of anaphylactoid and anaphylactic reactions during haemodialysis. Special consideration is given to the therapeutic and diagnostic approach.

Background: IgE-dependent triggering of basophils not only elicits the release of different mediators but also the up-regulation of certain markers, e.g. CD63, which can be detected by flow cytometry. We intended to investigate if flow cytometric analysis of basophil activation could be a valuable tool in the diagnosis of latex allergy, and to evaluate if the basophil activation test (BAT) could be helpful in determining the clinical significance of a positive latex IgE in individuals with negative history and negative latex skin test. Additionally we aimed to determine the role of cross-reactive carbohydrate determinants (CCDs) in causing positive latex IgE without apparent clinical significance., Methods: Twelve healthy controls without a history of latex hypersensitivity with a negative latex IgE and skin test (group 1), 24 individuals without a history of latex hypersensitivity with a negative latex IgE and skin test but with other inhalant allergies (group 2), and 29 latex allergic patients with a compelling history of latex allergy with a positive latex IgE and prick test (group 3) were enrolled. The diagnostic performances of the BAT were further evaluated in 13 individuals with a history of latex allergy but with negative specific IgE and/or skin test (group 4). Twenty-four individuals with positive latex IgE without apparent clinical relevance, i.e. without history of latex hypersensitivity and negative latex skin tests, were also analyzed (group 5). The putative role of CCDs causing positive latex IgE results without apparent clinical significance was evaluated by quantification of IgE for bromelain., Results: According, to the receiver operating characteristics(ROC)-generated threshold value of 17% between latex allergic patients and the pooled group of nonlatex allergic individuals, the sensitivity and specificity of the basophil activation test was 93.1% and 91.7%, respectively. In healthy controls, allergic patients without latex hypersensitivity and latex allergic patients the number of positive BATs was 0/12, 3/24 and 27/29, respectively. In the individuals with an evocative history of latex allergy but with negative latex IgE and/or skin test the BAT was positive in all 13 cases. Twenty of 24 individuals without apparent latex allergy but with positive latex IgE had a negative BAT. IgE for bromelain was positive in 1/19 sera from group 2, 1/24 sera from group 3, none of the 8 sera from group 4, but in 16/18 sera from group 5, respectively., Conclusion: Flow cytometric analysis of activated basophils seems a highly sensitive and specific tool for diagnosing latex allergy. In addition, the technique might help to determine the clinical relevance of positive IgE quantification in the absence of overt latex allergy. CCDs of natural rubber latex allergens were confirmed to mimic latex sensitization.

In a retrospective study, asthmatic patients allergic to either house-dust mite (HDM) (Dermatophagoides pteronyssinus) (n = 34) or to both HDM and grass pollen (GP) (n = 14), and who were treated with specific immunotherapy (SIT) during childhood (mean duration of SIT: 61 +/- 9.70 months), were re-evaluated in early adulthood after mean cessation of SIT for 9.3 +/- 2.76 years. The results were compared to those of a control group of asthmatic patients (n = 42) with comparable asthma features, who were treated with appropriate antiasthmatic drugs during childhood, but who never received SIT. Re-evaluation was carried out with a standardized questionnaire, skin prick tests (SPT), and lung-function assessments. At the time of re-evaluation, the mean age in the SIT-treated group was 23.1 +/- 3.50 years; in the control group, it was 22.7 +/- 3.40 years. At re-evaluation, the risk of frequent asthmatic symptoms was three times higher in the control group than in the SIT-treated group (prevalence ratio: 3.43; P = 0.0006). The frequent use of antiasthmatic medication was also more pronounced in the control group, although the difference was not statistically significant (P=0.38). Lung-function parameters and results of SPT with HDM were comparable in both groups. It is concluded that SIT has long-term effects on asthmatic symptoms in young adults.

Human seminal plasma anaphylaxis (HSPA) is rare but may be life-threatening. The antigen or antigens involved in these reactions reside in a glycoprotein fraction of human seminal plasma (HSP). We report a woman who experienced HSPA. Literature on the subject is reviewed.

Soluble interleukin-2 receptor (sIL-2R), eosinophil cationic protein (ECP), the lymphoproliferative response to house-dust mite (HDM), adhesion to human umbilical vein endothelial cells (HUVEC), and lymphocyte membrane markers were studied in three groups of children: healthy children, asthmatic children without hyposensitization (HS), and asthmatic children with HS. HS was associated with significantly lower numbers of peripheral blood eosinophils (PBE) and lower sIL-2R serum levels and with a tendency to lower ECP serum levels and lymphoproliferative response to HDM. There were no changes in the T-lymphocyte phenotypic markers CD4 and CD8 among the three groups. The interleukin-2 receptor (IL-2R, CD25) on HDM-stimulated T lymphocytes increased over unstimulated T lymphocytes in the three groups. The CD25 expression was higher on HDM-stimulated lymphocytes in both asthmatic groups than in healthy children. Adhesion of lymphocytes on HUVEC increased significantly after HDM stimulation in asthmatic children without HS, whereas no change was observed in the two other groups. However, there was no change in the expression of adhesion molecules CD29 and CD11a on lymphocytes in either of the groups. This study provides further evidence that HS can modify lymphocyte and eosinophil functions.

Eighteen children with perennial asthma and allergy to house-dust mite (HDM) underwent a bronchial challenge with HDM. Before and 24 h after the test, a venous blood sample was taken to determine levels of eosinophils, eosinophil cationic protein (ECP), soluble interleukin-2 receptor (IL-2R), and interleukin-6 (IL-6). A histamine challenge was performed before and 24 h after the HDM challenge. All subjects showed an immediate asthmatic reaction (IAR). A definite late asthmatic reaction (LAR) was observed in 15 children, a probable LAR in two, and no LAR in one. Because of persistent bronchial obstruction (FEV1 < 70%), eight children were unable to perform a histamine challenge 24 h after the allergen challenge. These were the children with the lowest prechallenge provocation dose (PD20) of histamine. In the other 10 children, the mean PD20 histamine decreased after the HDM challenge (mean PD20 before was 0.56 mg/ml; after challenge it was 0.14 mg/ml; P = 0.007). After the HDM challenge, an increase was detected in the mean values of blood eosinophils (mean before was 446/mm3; mean after was 733/mm3; P = 0.002), ECP (mean before was 26.3 micrograms/l; mean after was 34.3 micrograms/l; P < 0.040), and IL-2R (mean before was 116.35 U/ml; mean after was 128.52 U/ml; P < 0.040). On the other hand, IL-6 remained unchanged after the HDM challenge (mean before was 9.47 pg/l; mean after was 9.70 pg/l; P = 0.360).(ABSTRACT TRUNCATED AT 250 WORDS)

Two hundred and seventy patients with asthma and/or rhinitis (162 or 60% allergic, 108 or 40% non-allergic) were studied for sinus pathology by means of standard X-rays and tomograms. Sinus pathology was defined as abnormal sinus X-rays, either on standard or tomography. Fifty-four percent of the X-rays were classified as abnormal based on mucosal thickening, loss of translucency of the cavities of polyps. Asthma was significantly more often associated with sinus X-ray abnormalities (65.1%) than rhinitis and/or chronic cough (44.4%). Loss of translucency of the cavities is more frequent in children, whereas mucosa thickening becomes more frequent with progressing age. Since in this prospective study the taking of X-rays of the sinuses was not dependent on or related to temporarily occurring symptoms which could be attributed to acute sinusitis, the presence of sinus abnormalities on X-rays can be considered as an indicator of the chronicity of airways diseases and might provide an indication for prophylactic therapy of the associated airway disease in a continuous way. The importance of sinus tomograms is stressed, since only 32.5% of the patients with mucosa thickening could be detected on standard X-rays.

With the conventional, discrete RAST various tests are required to detect IgE of different specificities in the same serum. To overcome this problem and to reduce the costs, a multiple RAST with seven different mixtures was compared with the individual mixture constituents and with the 12 individual allergens currently in use in our department. One grass pollen mixture (gx3), two weed pollen mixtures (wx3, wx4), two tree pollen mixtures (tx5, tx6), one mould mixture (mx1) and one epithelial mixture (ex1) were used. A mixture of mites was not evaluated as there is only one important pathogenic organism in our regions (Dermatophagoides pteronyssinus or House dust mite). For grasses the gx3 mixture offered no advantage over the discrete RAST. The weed mixture wx3 was more sensitive than the most common discrete RAST's but at the cost of specificity. The wx4 mixture should not be used because the specificity is too low. The tree mixtures were not significantly more sensitive than the most common individual tree allergens, and were less specific. Mould mixtures should not be used because there is little cross-reactivity between the individual allergens, thus using a mixture would necessitate the subsequent determination of individual allergens, and the number of tests and the cost would be even higher. Neither should a mixture be used for epithelia because one wants to detect allergies to individual allergens. Moreover, the sensitivity of the epithelial mixture was too low. In general, we suggest the use of a limited panel of discrete RAST's instead of mixtures.

The frequency and severity of the late asthmatic reaction (LAR) was studied in asthmatic children allergic to house dust mite (HDM) or grass pollen (GP) with and without hyposensitization (HS). The four groups were comparable according to their severity of asthma. All children were allergic to HDM (Dermatophagoides pteronyssinus) or GP according to history, skin testing and specific IgE determination via the RAST. The LAR occurred less frequently (29% versus 73%) (P less than 0.001) and was less severe in children receiving HS. The difference was significant between the children allergic to HDM as well as between children allergic to GP. The immediate asthmatic reaction (IAR) was also less severe in children allergic to HDM who received HS, compared to those who never received HS, (P = 0.033) although the PD20 of the HDM challenge (PD20HDM) was not different between the two groups. In children allergic to GP, there was no difference in PD20 of the GP challenge (PD20GP) or in severity of the IAR, whether the children received HS or not. There was no difference between the PD20HDM in patients who developed a LAR and in patients who did not. There was no relation between the type of asthmatic reaction following the allergen provocation test and the level of circulating immune complexes (CIC) and the level of house dust mite-specific IgG (IgGHDM) or grass pollen-specific IgE (IgGGP) in the different groups, determined before the challenge. There was a decrease in the level of IgG containing CIC (IgGCIC) during the LAR. It is concluded that the LAR occurs less frequently and is less severe in asthmatic children who receive HS.

The occurrence of late asthmatic reactions after bronchial allergen challenge was studied in 50 house dust mite allergic patients subdivided in three groups: one group had asthma without nasal symptoms, another group had rhinitis without pulmonary symptoms and a third group had a combination of both asthma and rhinitis. Late asthmatic reactions were present in 80% of asthmatic patients and in 18.7% of rhinitis patients. The degree of non-specific bronchial reactivity to histamine (provocative dose 15 or PD15 histamine) and the degree of immediate reactivity to allergen (PD15 house dust mite) did not differ significantly between patients with and without late asthmatic reactions. These findings suggest that an important difference between asthma and rhinitis is the lack of late asthmatic reactions in rhinitis patients, whereas the degree of immediate bronchial reactivity to the allergen is similar in asthma and rhinitis.

Forty-three patients with type I allergic respiratory diseases received aqueous grass pollen immunotherapy in a prospective study designed to compare the clinical and biological effects of a semi-rush hyposensitization (20 patients) with ordinary hyposensitization (23 patients). Before the start of the therapy (end of previous grass pollen season, t1) and before (t2) and after the next grass pollen season (t3), total serum IgE (tIgE), grass pollen-specific IgE (GPsIgE), grass pollen-specific IgG (GPsIgG) and complement factors C3 and C4 were determined. GPsIgE and GPsIgG levels increased significantly more during immunotherapy in patients receiving the semi-rush scheme as compared with the ordinary scheme. There were no significant changes between the two schemes at any times for tIgE, C3 and C4. GPsIgG was already higher in allergic patients before the start of therapy as compared with non-allergic patients and controls. Clinical improvement was the same in patients treated with the semi-rush scheme as in the ordinary group. The number of side effects was not statistically different between the two groups. In neither group was there a correlation between the change in biological parameters and change in clinical symptoms. As the semi-rush scheme gives the same results immunologically as well as clinically, it could be used in a number of patients since it reduces the time course of the initial therapy by about 2 months.

Twenty children aged 3 to 14 years with a history of bronchial asthma complicated by chronic sinusitis were studied in a double-blind study. Patients received, at random, over a period of 2 weeks, either 2 ml saline or 2 ml bromhexine (2 mg/ml) t.i.d. by means of a home nebulizer. A significant decline of clinical symptoms during both nebulization treatments as compared to the pretreatment symptom score was observed (mean score of 1.5 +/- 0.7 and 0.5 +/- 0.8, respectively, P less than 0.01). Both types of nebulization were equally efficient in reducing the symptom score. Radiological abnormalities were significantly more reversed after saline nebulization as compared with bromhexine (P less than 0.05), although both treatments showed radiological improvement (P less than 0.01). The present study indicates that nebulization with saline may have some beneficial effect on chronic sinusitis in asthmatic children. Bromhexine was not superior to saline for this purpose.

In this study the role of food additives, tyramine and acetylsalicylic acid, was investigated by double-blind placebo-controlled challenges (DBPCC) in 25 children with severe atopic dermatitis (AD). All children challenged with foods (n = 24), except one, showed one or more positive reactions to the DBPCC with foods. Positive reactions presented as different combinations of flares of skin symptoms, intestinal symptoms and respiratory symptoms. Seventeen children (70.8%) showed a positive challenge to egg, 12 to wheat (50%), eight to milk (33.3%) and eight to soya (33.3%). Six children underwent DBPCC with food additives, tyramine and acetylsalicylic acid. All were found to demonstrate positive skin and/or intestinal reactions to at least one of the food additives. Two children reacted to tartrazine, three to sodium benzoate, two to sodium glutamate, two to sodium metabisulfite, four to acetylsalicylic acid and one to tyramine. It is concluded that some foods, food additives, tyramine and acetylsalicylic acid, can cause positive DBPCC in children with severe AD.