Notes: A patient developed anaphylaxis during anaesthesia, towards the end of surgery, 30 s after intravenous administration of neostigmine. Anaphylaxis to neostigmine was confirmed by demonstrating an elevated mast cell tryptase and a strongly/positive skin prick test, showing the presence of drug-specific IgE (skin prick tests to neostigmine were negative in normal subjects). This is a rare cause of anaphylaxis during anaesthesia.

Notes: IgG1 and IgG4 antivenom antibody responses were compared in groups of patients who had experienced systemic reactions to wasp (Vespula spp.) or bee stings. Pretreatment serum IgG4 antibody levels were low in both groups, but IgG4 antibodies were significantly raised in bee-allergic patients (P〈0.002), probably reflecting their greater exposure to stings than wasp-reactive patients. No direct or indirect relationships were found, in untreated bee or wasp patients, between IgG1, IgG4, or IgE antibody levels and the severity of a patient's last systemic reaction to a sting. After a 12-week course of venom immunotherapy (VIT), IgG1 antibodies increased significantly only in wasp-sensitive patients (P〈0.001), although both groups responded with marked increases in venom-specific IgG4 (P〈0.01). Wasp-allergic subjects who responded to VIT with high production of specific IgG4 showed the greatest increases (pre- to post-VIT) in IgE antibodies (P〈0.05). This group also demonstrated a direct correlation (P〈0.05) between post-VIT levels of IgE and IgG1 antibodies, a finding contrary to an IgE-immunoregulatory role for IgG 1. High levels of venom-specific IgG1 alone, or in combination with IgG4, were not protective in three patients who suffered repeated adverse reactions to bee VIT, showing that absolute levels of IgG subclass antivaenom antibodies are not reliably indicative of clinical responsiveness in individual patients.

Notes: The Pharmacia CAP System is a new assay for serum specific IgE, utilising a solid phase capable of binding more antigen than conventional systems. The CAP System has been evaluated in 69 consecutive patients referred to one allergy clinic in relation to skin prick test (SPT), radioallergosorbent test (Phadebas RAST®) and specific allergy diagnosis for five inhalant allergens, D.ptewnyssinus, timothy grass pollen, eat epithelium/dander, Cladosporium and Alternaria. Good correlation was obtained between RAST and CAP for all allergens, e.g. r=0.974 for D.pteronyssinus and r=0.964 for grass pollen. When sensitivity and specificity were examined for both CAP and RAST versus SPT, CAP was usually found to be of greater sensitivity than RAST, and of similar or slightly lower specificity. SPT gave more positive reactions than either in vitro test, but CAP gave more positives than RAST. Twenty-two of 336 (6.6%) tests were CAP positive/RAST negative, whereas a negative CAP with a positive RAST occurred in only 2/336 (0.6%) tests. Of patients with any test (SPT or RAST or CAP) for specific IgE positive, up to 20–30% did not have clinical allergy, confirming the importance of the history in interpreting these tests. Our results suggest that, for the allergens tested, the Pharmacia CAP System is more sensitive than the RAST, identifying more positive tests and approximating more closely to the SPT. It offers the additional advantages of speed and efficiency.

Notes: Background: The mechanism of immunotherapy is unclear. Allergic disease is known to involve enhanced TH-2 cytokine responses to allergen.Objective: In order to investigate the mechanisms of immunotherapy, we have examined changes in cytokine secretion before (13 patients) and during (nine patients) both rush and conventional venom immunotherapy (VIT) in nee venom allergic patient. Method Peripheral blood mononuclear cells were stimulated in vitro with see venom, non-specific antigen or mitogen and secretion of IL-4 (TH-2) and IFNγ (TH-1) over the culture period measured.Results: Untreated patients had TH-2 responses to venom and TH-1 responses to antigen and strong proliferative responses to venom. Controls showed no response (proliferation or cytokines) to venom and the normal TH-1 response to antigen. VIT resulted in marked changes in cytokine secretion to venom, with reduction of the abnormal TH-2 response and induction of a TH-1 response. The pattern differed in rush and conventional VIT. One day after rush VIT there was a significant fall in IL-4 secretion (P 〈 0.01), which rose by 3 weeks then declined. In conventional ViT there was a gradual reduction of IL-4 production significant after 2 months and undetectable by 6 months. IFNγ secretion was induced by VIT. Proliferative responses mirrored the IL-4 changes. One day after rush VIT there was a loss of T cells, monocytes and NK cells from peripheral blood.Conclusion: This study shows that immmotherapy shifted cytokine responses to allergen from a TH-2 to a TH-1 dominant pattern, suggesting direct effects on T cells. How these cytokine changes relate to clinical desensitization is not clear. In the longer term they would result in an isotype switch from IgE to IgG. Early changes in cytokine or chemokine production might down regulate mast cell or basophil reactivity and explain the rapid desensilization in rush VIT.

Notes: Proliferative responses and production of IL-2 by peripheral blood mononuclear cells of patients with Dermatophagoitles pieronyssinus rhinitis ± asthma were measured at up to 24 hr intervals from 1–8 days, after stimulation with mitogen (PHA), antigen (SKSD) and specific allergen (D.pteronysxinus). IL-2 was measured in culture supcrnaunts using the murine CTLL cell line bioassay. Compared to non-atopic controls, patients had significantly higher prolilenitive responses to D. pteronyssinus and SKSD but similar responses to PHA. In patients, maximal proliferate responses to PHA, SKSD and D. piemnyxsinus were at 3, 6 and 7 days, respectively. IL-2 levels in response to stimulation with D. pieronvssinus were significantly higher in patients than controls, where only background levels were found (15.4, 7.9–30.7− 10-2 U/ml [mean, range] n=11;vs 2.2,0.1–8.4 × 10-2 U/ml, n= 6; P〈 0.05). In contrast, IL-2 production to PHA and SKSD, although higher in patients, was not significantly different than controls. These results suggest allergic patients possess a population of T cells expandable by specific allergen which are induced to secrete IL-2.

Notes: Background Allergic reactions to food are well recognized in both children and adults, but because of their relative infrequency their typical features may not be readily recognized by patients and their medical care givers who are not allergists.Objective We sought to investigate the circumstances and clinical characteristics of food allergies in adults and children in the community.Methods Self-completed questionnaire responses over a 6-month period from 109 members of the Anaphylaxis Campaign, the major British patient resource group for people who have suffered severe allergic reactions.Results One hundred and nine respondents reported 126 reactions during the study period. Seventy-five were children (under 16 years, median age 6 years at the time of reaction). Predictably more boys than girls were reported to have had reactions but more women reported reactions than men (P〈0.05). Although the groups were equally aware of their food allergies the children had undergone diagnostic tests more often (P〈0.001). Foods were implicated in 112 (89%) of reports. Restaurants were implicated less often (14%) than in other series, probably reflecting British eating habits. Children with asthma reported more severe reactions than those without asthma (P=0.008), although frequency or severity of recent asthma symptoms was not associated with severity of allergic reaction reported. When available, self-injectable adrenaline was used in 35% of severe reactions and 13% of non-severe reactions (P=0.01). A quarter of adults who received one dose of adrenaline also received a second dose.Conclusion The allergens implicated in this report reflect previous data from similar patient groups in North America. Asthmatic children suffer more severe reactions than non-asthmatic children. It appears that British adults need better access to expert care of their allergies. Even when it is prescribed and available self-injectable adrenaline appears under-used in severe reactions. The incidence of severe but non-fatal allergic reactions in the UK may have been underestimated in the past.

Notes: Background There are few data on the long-term management of children with peanut/nut allergy. Advice is variable and often inadequate; further reactions are common. There is no consensus on the criteria for prescription of rescue medication, particularly adrenaline.Method A longitudinal prospective and case–control study in a tertiary allergy clinic. Patients/parents/school staff of 747 children with confirmed peanut or tree nut allergy received detailed verbal and written advice on nut avoidance, training in recognition and (self-) treatment of reactions and a written treatment plan. The severity of nut allergy was graded (mild–severe) and emergency medication was allocated according to our criteria: all received oral antihistamines, injected adrenaline (EpiPen) was given to those with reactions with airway narrowing, milder reactions to low-dose exposure or concomitant asthma. At annual follow-up over 25 906 patient-months (median: 39 months) retraining was given and details of further reactions (frequency, severity and treatment) were obtained. Criteria for allocation of EpiPen were evaluated.Results The worst reaction pre-enrolment was mild in 64% and moderate/severe in 36% (airway narrowing). Of 615 subjects followed up, 21% had a further reaction (eightfold reduction in frequency), mostly mild. There was a 60-fold reduction in the frequency of severe reactions. Of those with a moderate–severe initial reaction, 99.5% had no or a less severe follow-up reaction. No child with a mild or severe index reaction had a severe follow-up reaction. Only 1/615 (0.2%) had a severe follow-up reaction and only 2/615 (0.3%) used adrenaline, both successfully and had it available according to our criteria. Of mild–moderate reactions, 77% required oral antihistamines alone and 15% no treatment. Children who had follow-up reactions had more frequent and severe reactions pre-enrolment.Conclusion The management plan greatly reduced the frequency and severity of further reactions and was successful for all children. Our criteria for selective prescription of EpiPen in the context of this management plan were appropriate. This is the first study to provide evidence on which to inform practice.

Notes: This paper investigates the relationship between venom IgG levels and protection from stings. Venom-specific IgG antibody levels have been measured by radioimmunoassay in untreated wasp- (n= 38) and bee-allergic (n=16) patients presenting with systemic reactions to stings and in a sub-group of these (wasp= 15; bee = 9), before and after the initial course of venom immunotherapy (VIT). A history was taken of all reactions, the last systemic reaction being graded on a scale of 1–8 and of the number and timing of stings. In untreated patients venom IgG levels were much higher in bee-allergic patients (mean ± s.e. = 68.2 ± 7.1 % positive pool) than in the wasp group (27.1 ± 4.2%) (P〈 0.05 Mann-Whitney U-test). There was a marked rise in venom IgG after the initial course of VIT in the wasp group (geometric mean and 95% confidence intervals = 40.5%, 28.8−54.3) but a much smaller rise in the bee group (15.3%, 6.6–24.1), with no overlap in the 95% confidence intervals. Bee patients, who were mainly beekeepers or their relatives, had been more heavily immunized with venom than wasp patients. They had received: (i) more stings (mean number of stings: bee, 26; wasp, 4; P〈 0.001) and (ii) more stings per year. Wasp patients received their smaller number of stings over a much longer period, up to 40 yr. There was no correlation between the severity of the last systemic reaction and the venom IgG levels alone or venom IgG and IgE levels in combined analysis in either bee or wasp patients. This study shows that the pattern of IgG response differs in bee and wasp-allergic subjects, and that most bee-allergic subjects with systemic reactions have high levels of venom IgG. The degree of immunization with venom seems to be an important determinant of the venom IgG level. Our findings suggest thai venom-specific IgG levels do not predict systemic reactions to stings and are not useful for monitoring VIT. If protection from stings is IgG-mediated, our observations suggest that the relevant immune response is more complex, possibly involving IgG sub-classes, IgG antibodies to individual venom antigens or antibody affinity, and not adequately reflected by measurement of the concentration of venom-specific IgG.

Notes: Background Peanut and tree nut allergy are common, increasing in prevalence and the commonest food cause of anaphylaxis. In the USA, 7.8% are sensitized (have nut-specific IgE), but not all those sensitized are allergic. Lack of data makes interpretation of tests for nut-specific IgE difficult.Objectives This is the first study to investigate the clinical significance of test results for peanut and tree nut allergy in allergic or tolerant patients. Findings are related to the severity of the allergy.Method An observational study of 1000 children and adults allergic to at least one nut. History of reactions (severity graded) or tolerance to up to five nuts was obtained and skin prick test (SPT)/serum-specific IgE (CAP) performed.Results There was no correlation between SPT size and graded severity of worst reaction for all nuts combined or for peanut, hazelnut, almond and walnut. For CAP, there was no correlation for all nuts. Where patients tolerated a nut, 43% had positive SPT of 3–7 mm and 3% ≥ 8 mm. For CAP, 35% were positive (0.35–14.99 kU/L) and 5% ≥ 15 kU/L. In SPT range 3–7 mm, 54% were allergic and 46% were tolerant. There was poor concordance between SPT and CAP (66%). Of patients with a clear nut-allergic history, only 0.5% had negative SPT, but 22% negative CAP.Conclusions Magnitude of SPT or CAP does not predict clinical severity, with no difference between minor urticaria and anaphylaxis. SPT is more reliable than CAP in confirming allergy. Forty-six per cent of those tolerant to a nut have positive tests ≥ 3 mm (sensitized but not allergic). One cannot predict clinical reactivity from results in a wide ‘grey area’ of SPT 3–7 mm; 22% of negative CAPs are falsely reassuring and 40% of positive CAPs are misleading. This emphasizes the importance of the history. Understanding this is essential for accurate diagnosis. Patients with SPT ≥ 8 mm and CAP ≥ 15 kU/L were rarely tolerant so these levels are almost always (in ≥ 95%) diagnostic.