The clinical spectrum of omega-5-gliadin allergy.

BACKGROUND: IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. AIMS: This study documents clinical manifestations in a large series of patients with sIgE to O5G. METHODS: A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. RESULTS: Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. CONCLUSION: WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

A patient with anaphylaxis after alteplase infusion.

Anaphylaxis to alteplase is a rare but reported complication of intravenous thrombolysis. We report a patient with a documented episode of anaphylaxis that occurred following an initial bolus and a subsequent delayed infusion of alteplase for thrombolysis of acute ischaemic stroke. The patient was treated with hydrocortisone, adrenaline, prochlorperazine and ranitidine, as per the hospital anaphylaxis protocol, intubation and admission to the intensive care unit. Serum tryptase levels performed during the anaphylactic event (at the end of the infusion) and 1.5 hours later showed an increase of 2 µg/L, suggestive of an anaphylactic reaction. Anaphylaxis remains largely a clinical diagnosis even in the absence of an elevated serum tryptase. The patient would benefit from further allergen testing given the severity of the reaction to alteplase. We report this patient to indicate that although rare, anaphylaxis is a recognised adverse event following alteplase. In the case of any symptoms suggestive of a minor anaphylactic reaction to alteplase, further infusion should be ceased to avoid a dose dependent major reaction.

Myrmecia pilosula (Jack Jumper) ant venom: identification of allergens and revised nomenclature.

BACKGROUND: The 'Jack Jumper Ant' (JJA; Myrmecia pilosula species complex) is the major cause of ant sting anaphylaxis in Australia. Our aims were to determine the allergenicity of previously described venom peptides in their native forms, identify additional allergens and if necessary, update nomenclature used to describe the allergens according to International Union of Immunological Societies criteria. METHODS: Various polyacrylamide gel electrophoresis methods were used to separate JJA venom. Gel resolved venom was Western-blotted and probed with individual sera taken from patients with a history of JJA sting anaphylaxis and immunoglobulin E radioallergosorbent test (IgE RAST) tracer uptakes of >1% to whole venom. RESULTS: Of 67 available sera, 54 had RAST uptakes >1%. Thirteen IgE binding bands were identified using these sera. Pilosulin 3, [Ile(5)]pilosulin 1, and pilosulin 4.1 were recognized by 42 (78%), 18 (33%) and nine (17%) of the 54 sera that were tested. Immunoglobulin E-binding proteins with estimated molecular masses of 6.6, 22.8, 25.6, 30.4, 32.1, 34.4 and 89.8 kDa were each recognized by three or more individual sera. Two of these (25.6 and 89.8 kDa) were recognized by 46% and 37% of sera, respectively. CONCLUSION: Nomenclature used to describe JJA venom allergens has been revised. Pilosulin 3 (Myr p 2) is the only major allergen, whilst [Ile(5)]pilosulin 1 (Myr p 1), and pilosulin 4.1 (Myr p 3) are minor allergens. There are an additional five IgE-binding proteins that require further characterization before they can be named as allergens. These findings provide a framework for standardizing venom extracts for diagnosis and immunotherapy.

In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo-controlled, crossover trial.

BACKGROUND: In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful. OBJECTIVE: We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy. METHODS: During a double-blind randomized placebo-controlled crossover trial of Myrmecia pilosula ant VIT the following venom-specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. RESULTS: Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL-4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom-induced leucocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected. CONCLUSION: The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre-incubation with IL-3. None of the tests evaluated appear to be reliable markers of successful VIT.

Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation.

OBJECTIVES: To assess a protocol for treatment of sting anaphylaxis. DESIGN: Prospective assessment of treatment with oxygen, intravenous infusion of adrenaline (epinephrine), and volume resuscitation with normal saline. SETTING: Sub-study of a venom immunotherapy trial. PARTICIPANTS: 21 otherwise healthy adults with systemic allergic reactions to diagnostic sting challenge. MAIN OUTCOME MEASURES: Response to treatment, total adrenaline dose and infusion duration, recurrence of symptoms after stopping the infusion, and additional volume resuscitation. RESULTS: 19 participants required intervention according to the protocol. All received adrenaline, and five received volume resuscitation. In nine cases, physical signs of anaphylaxis recurred after initial attempts at stopping adrenaline but resolved after recommencing the infusion. The median total dose and infusion duration were 590 micro g and 115 minutes respectively, but were significantly higher for eight patients who had hypotensive reactions (762 micro g and 169 minutes respectively). Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. Widespread T wave inversion occurred, before starting treatment with adrenaline, in one person with an otherwise mild reaction. All patients fully recovered and were fit for same day discharge, apart from the person with ECG changes who was observed overnight and discharged the following day. CONCLUSIONS: Carefully titrated intravenous adrenaline combined with volume resuscitation is an effective strategy for treating sting anaphylaxis, however severe bradycardia may benefit from additional treatment with atropine. Cardiac effects of anaphylaxis, perhaps including neurocardiogenic mechanisms, may be an important factor in some lethal reactions.

Fatal anaphylaxis following jack jumper ant sting in southern Tasmania.

The "jack jumper" ant (Myrmecia pilosula) is a major cause of anaphylaxis in Tasmania. We describe four deaths attributed to stings by this ant between 1980 and 1999. All victims were men aged 40 years or over with significant comorbidities; two were taking angiotensin-converting enzyme inhibitors, which may increase risk of severe anaphylaxis. Three victims had known ant-sting allergy, but only one carried adrenaline, which he did not use. Another believed he was protected by previous attempts at hyposensitisation with whole ant-body extract. There is potential to prevent deaths by careful education of people with known allergy, prescribing of adrenaline for auto-injection and development of an effective hyposensitisation therapy.

Bee venom hypersensitivity and its management: patients perception of venom desensitisation.

The objectives of the study were to review bee venom immunotherapy from the patient's perspective: in particular its benefits and its problems, and to investigate any genetic tendency for bee venom hypersensitivity. A self administered, 9 item questionnaire was sent to 219 patients who had undergone either inpatient or outpatient bee venom immunotherapy at Flinders Medical Center. The clinic records of these patients were also reviewed. The controls for the genetic study were sought from patients, staff and students at Flinders University and Flinders Medical Centre. One hundred and forty-six questionnaires (some incomplete and anonymous) were received. The female to male ratio was 1:2.5. The age at the time of the initial anaphylactic reaction to a bee sting ranged between 2 to 59 years, with 67% of patients being less then 20 years old. Forty percent of patients underwent venom immunotherapy for a period less than 2 years with only 11% maintaining therapy for the recommended period of 5 years or more. Thirty three percent of patients stopped their therapy on their own accord. Bee stings occurring during bee venom immunotherapy (n = 56) were generally well tolerated except in 8 subjects, 7 of whom had not reached the maintenance dose. The reduction in systemic reactions to subsequent bee stings was significantly better in the study group receiving bee venom than in an historic control group treated with whole bee extract (p = 0.03). Fear of bee stings and restricted life styles were improved during or after venom immunotherapy. The frequency of a positive family history of systemic reactions to bee stings in the patient cohort was 31%, whereas in controls it was 15% (p = 0.013). Bee venom immunotherapy has dual benefits: patients are protected from subsequent sting anaphylaxis and there is reduced psychological morbidity. However, to be effective, venom immunotherapy requires a prolonged period of carefully supervised treatment and each venom injection can cause local and systemic side effects. Genetic factors appear to be present in those patients who develop immediate hypersensitivity to be stings.

IgE+ cells in the peripheral blood of atopic, nonatopic, and bee venom-hypersensitive individuals exhibit the phenotype of highly differentiated B cells.

We have analyzed IgE+ cells in peripheral blood of atopic donors, donors hypersensitive to bee venom, and nonatopic control donors with two- and three-color flow cytometry. Although the percentage of IgE+ cells varied among these groups, the overall phenotypic patterns were similar. Most IgE+ cells do not display typical B-cell markers, such as CD19, CD20, and CD21. A significant proportion of these cells stain for CD38, indicating that they are more differentiated. IgE+ cells express Fc gamma RII and CD45RO, an isoform associated with an advanced level of differentiation. The majority of IgE+ cells do not coexpress other surface immunoglobulin isotypes. In the case of bee venom-hypersensitive donors, we have been able to identify a small population of IgE+ cells with a specificity for phospholipase A2, a major immunogenic component of bee venom. The phospholipase A2+ cells display a phenotype similar to that of the IgE+ cells.

Common allergic skin conditions.

Skin conditions regarded as having an 'allergic' origin are extremely common. Immunologically specific hypersensitivities to food and aeroallergens and idiosyncratic reactions to food chemicals play a role in some of the individuals suffering from these conditions, but in others intrinsic or unknown factors dominate. Rashes are frequently seen in relation to food intolerance and adverse drug reactions that share common mechanisms.

Immunoblot analysis of IgE and IgG antibodies to honey bee venom: cross sectional and sequential studies in bee sensitive subjects.

To investigate the specific IgE and IgG immune response to honey bee venom (bv), we performed immunoblot analysis of sera from 47 bee sensitive subjects and followed the response during and after venom immunotherapy in 15 of these subjects. Fifteen venom proteins varying in molecular size from 20 to 105 kDa were identified as being antigenic and consisted of a high molecular weight (HMW) group (5 to 105 kDa, containing the previously identified allergens B and C) and a low molecular weight group (LMW) containing hyaluronidase and phospholipase A. In general for a given individual the anti-venom IgE and IgG response was qualitatively similar although some variation between individuals was apparent. Reactivity with hyaluronidase and phospholipase A appeared only in those subjects showing reactivity with HMW components. During immunotherapy specific anti-venom IgG and IgE responses tended to be linked. Increased responses being seen against all components in 4 of 12 subjects, reductions in 3 and unchanged responses in the remainder. Following immunotherapy (mean 4.0 years), spontaneous reduction of IgE and IgG was seen in 5 of 5 subjects. Loss of reactivity with the LMW components was prominent in these sera.

Vega testing in the diagnosis of allergic conditions. The Australian College of Allergy.

Vega testing (the Vega test method) is an unorthodox method of diagnosing allergic and other diseases. It has no established scientific basis and there are no controlled trials to support its usefulness. Vega testing may lead to inappropriate treatment and expense to the patient and community.

Increased intestinal permeability in atopic eczema.

We have investigated gastrointestinal permeability in children with atopic eczema by measuring the relative urinary excretion rates of the inert di- and monosaccharides lactulose and rhamnose following their oral administration. The median lactulose/rhamnose ratio was greater in 26 children with atopic eczema than in a control group of 29 children which included both healthy individuals and others with various noneczematous dermatoses. This increased permeability may be a primary abnormality of the gut or may reflect intestinal mucosal damage caused by local hypersensitivity reactions to food antigens.

Bee sting anaphylaxis in an urban population of South Australia.

The clinical manifestations and circumstances of bee sting anaphylaxis have been studied retrospectively in 98 subjects. Most reactions occurred in children but the most severe reactions were seen in adult males, of whom 7 lost consciousness and 2 required cardiopulmonary resuscitation. Most stings causing anaphylaxis occurred on the unprotected feet whilst the subject was on lawn in the afternoons in December, January and February when the maximum daily temperature was between 20 and 30 degrees C. This is the temperature range when bees are particularly active in gathering pollen. However, a significantly greater frequency of anaphylactic reactions occurred at higher temperatures when bees are less active, suggesting that high environmental temperature may predispose the individual to greater exposure to bees or possibly to anaphylactic reactions per se. The presence of atopy did not appear to predispose subjects to bee venom hypersensitivity. Considerable anxiety and lifestyle alteration were identified in some subjects. The alleviation of this anxiety is considered an appropriate indication for bee venom immunotherapy.

Urticaria and angio-oedema.

Urticaria and angio-oedema are a symptom complex covering a wide range of clinical disorders. Specific types are now well described, and it appears that many cases of idiopathic chronic urticaria which make up the vast majority of patients referred for assessment are due to intolerance to natural salicylates, preservatives and colouring agents. There is, therefore, an urgent need for legislation to enforce the clear identification of these chemicals in processed food and drugs.

Extrinsic factors in atopic eczema.

The debate over the role of extrinsic allergens in atopic eczema has been enlightened in recent years by some well-controlled studies and improvements in our understanding of conditions which lead to hypersensitivity. This paper reviews some of these findings, which have preventative and therapeutic implications. No attempt is made here to review other aspects of this multifactorial disease, nor to enter into detailed discussion of dietary or allergen avoidance regimens, which have been covered in several recent reviews. Such regimens are not without risk, and require expert supervision.