Evaluation of outcome after cardiomyotomy for achalasia using the Chicago classification.

BACKGROUND: Achalasia can be subdivided into manometric subtypes according to the Chicago classification. These subtypes are proposed to predict outcome after treatment. This hypothesis was tested using a database of patients who underwent laparoscopic Heller's cardiomyotomy with anterior fundoplication. METHODS: All patients who underwent Heller's cardiomyotomy for achalasia between June 1993 and March 2015 were identified from an institutional database. Manometry tracings were retrieved and re-reported according the Chicago classification. Outcome was assessed by a postal questionnaire, and designated a success if the modified Eckardt score was 3 or less, and the patient had not undergone subsequent surgery or pneumatic dilatation. Difference in outcome after cardiomyotomy was analysed with a mixed-effects logistic regression model. RESULTS: Sixty, 111 and 24 patients had type I, II and II achalasia respectively. Patients with type III achalasia were more likely to be older than those with type I or II (mean age 63 versus 50 and 49 years respectively; P = 0·001). Some 176 of 195 patients returned questionnaires after surgery. Type III achalasia was less likely to have a successful outcome than type II (odds ratio (OR) 0·38, 95 per cent c.i. 0·15 to 0·94; P = 0·035). There was no significant difference in outcome between types I and II achalasia (II versus I: OR 0·87, 0·47 to 1·60; P 0·663). The success rate at 3-year follow-up was 69 per cent (22 of 32) for type I, 66 per cent (33 of 50) for type II and 31 per cent (4 of 13) for type III. CONCLUSION: Type III achalasia is a predictor of poor outcome after cardiomyotomy. There was no difference in outcome between types I and II achalasia.

Impaired bolus clearance in asymptomatic older adults during high-resolution impedance manometry.

BACKGROUND: Dysphagia becomes more common in old age. We performed high-resolution impedance manometry (HRIM) in asymptomatic healthy adults (including an older cohort >80 years) to assess HRIM findings in relation to bolus clearance. METHODS: Esophageal HRIM was performed in a sitting posture in 45 healthy volunteers (n = 30 young control, mean age 37 ± 11 years and n = 15 older subjects aged 85 ± 4 years) using a 3.2-mm solid-state catheter (Solar GI system; MMS, Enschede, The Netherlands) with 25 pressure (1-cm spacing) and 12 impedance segments (2-cm intervals). Five swallows each of 5- and 10-mL liquid and viscous bolus were performed and analyzed using esophageal pressure topography metrics and Chicago classification criteria as well as pressure-flow parameters. Bolus transit was determined using standard impedance criteria. A p-value <0.05 was considered significant. KEY RESULTS: Impaired bolus clearance occurred more frequently in asymptomatic older subjects compared with young controls (YC) during liquid (40 vs 18%, χ2  = 4.935; p < 0.05) and viscous (60 vs 17%; χ2  = 39.08; p < 0.001) swallowing. Longer peristaltic breaks (p < 0.05) and more rapid peristalsis (L: p < 0.004, V: p = 0.003) occurred in the older cohort, with reduced impedance-based clearance for both bolus consistencies (L: p < 0.05, V: p < 0.001). Decreased peristaltic vigor (distal contractile integral <450 mmHg/s/cm) was associated with reduced liquid clearance in both age groups (p < 0.001) and of viscous swallows in the older group (p < 0.001). Impedance ratio, a marker of bolus retention, was increased in older subjects during liquid (p = 0.002) and viscous (p < 0.001) swallowing. CONCLUSIONS & INFERENCES: Impaired liquid and viscous bolus clearance, esophageal pressure topography, and pressure-flow changes were seen in asymptomatic older subjects.

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.

Maximum upper esophageal sphincter (UES) admittance: a non-specific marker of UES dysfunction.

BACKGROUND: Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. METHODS: Sixty-six healthy subjects (n = 50 controls 20-80 years; n = 16 elderly >80 years), 11 patients with CPB (51-83 years) and 16 with MND (58-91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. KEY RESULTS: In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. CONCLUSIONS & INFERENCES: The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction.

Swallowing dysfunction in healthy older people using pharyngeal pressure-flow analysis.

BACKGROUND: Age-related loss of swallowing efficiency may occur for multiple reasons. Objective assessment of individual dysfunctions is difficult and may not clearly differentiate these from normal. Pharyngeal pressure-flow analysis is a novel technique that allows quantification of swallow dysfunction predisposing to aspiration risk based on a swallow risk index (SRI). In this study, we examined the effect of ageing on swallow function. METHODS: Studies were performed in 68 healthy subjects aged 20-91 years (mean 59 years; 29 male), asymptomatic for oropharyngeal disease. Swallowing of liquid and viscous boluses was recorded with a pressure-impedance catheter. Indices of swallow function including the SRI, postswallow residues, upper esophageal sphincter opening and bolus transit time were derived using purpose designed software. KEY RESULTS: Swallow function worsened with increasing age with a significant decline after 80 years. Higher SRI correlated with increasing age (r = 0.257, p < 0.05 for liquids and r = 0.361, p < 0.005 viscous bolus). Subjects over 80 years were overrepresented amongst those with an SRI considered diagnostically relevant (SRI > 15). In addition, upper esophageal sphincter opening was reduced and postswallow residues increased in older subjects. CONCLUSIONS & INFERENCES: Pharyngeal pressure-flow analysis reveals multiple functional abnormalities in older individuals. The higher SRI levels seen in asymptomatic elders possibly reflect a loss of functional reserve with ageing. Automated impedance manometry analysis of swallow function may allow the risk of developing disordered swallowing to be quantified numerically.

Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies.

BACKGROUND: Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. METHODS: Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. RESULTS: No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P = 0.10). CONCLUSIONS: Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance.

Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants' allergies in first year of life: randomised controlled trial.

OBJECTIVE: To determine whether dietary n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age. DESIGN: Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO) randomised controlled trial. SETTING: Adelaide, South Australia. PARTICIPANTS: 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial. INTERVENTIONS: The intervention group (n=368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n=338) received matched vegetable oil capsules without n-3 LCPUFA. MAIN OUTCOME MEASURE: Immunoglobulin E associated allergic disease (eczema or food allergy with sensitisation) at 1 year of age. RESULTS: No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups (32/368 (9%) v 43/338 (13%); unadjusted relative risk 0.68, 95% confidence interval 0.43 to 1.05, P=0.08; adjusted relative risk 0.70, 0.45 to 1.09, P=0.12), although the percentage of infants diagnosed as having atopic eczema (that is, eczema with associated sensitisation) was lower in the n-3 LCPUFA group (26/368 (7%) v 39/338 (12%); unadjusted relative risk 0.61, 0.38 to 0.98, P=0.04; adjusted relative risk 0.64, 0.40 to 1.02, P=0.06). Fewer infants were sensitised to egg in the n-3 LCPUFA group (34/368 (9%) v 52/338 (15%); unadjusted relative risk 0.61, 0.40 to 0.91, P=0.02; adjusted relative risk 0.62, 0.41 to 0.93, P=0.02), but no difference between groups in immunoglobulin E associated food allergy was seen. CONCLUSION: n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life, although atopic eczema and egg sensitisation were lower. Longer term follow-up is needed to determine if supplementation has an effect on respiratory allergic diseases and aeroallergen sensitisation in childhood. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000735055 (DOMInO trial: ACTRN12605000569606).

Utility of peripheral blood B cell subsets analysis in common variable immunodeficiency.

Abnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multi-colour flow cytometry (MFC) in a cohort of well-characterized CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) compared to normal controls (P < 0·0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P = 0·0034). The previously published associations with autoimmune diseases could not be confirmed. The Euroclass classification was not predictive of clinical phenotypes. The absolute numbers of all B cell subsets were reduced in CVID patients compared to controls. There was a significant linear correlation between low absolute total B cells and MBC with granulomatous disease (P < 0·05) and a trend towards lower B cells in patients with autoimmune diseases (P = 0·07). Absolute number of different B cell subsets may be more meaningful than their relative percentages in assessing the risk of granulomatous diseases and possibly autoimmunity.

Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies.

BACKGROUND AND AIMS: Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. METHODS: Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2-0.8 g/kg 3-4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. RESULTS: There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996-1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment-related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs. CONCLUSION: Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.

Oral drug challenges in non-steroidal anti-inflammatory drug-induced urticaria, angioedema and anaphylaxis.

BACKGROUND: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). AIM: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. METHODS: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. RESULTS: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. CONCLUSION: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs.

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.

Physiology of diffuse esophageal spasm (DES)--when normal swallows are not normal.

BACKGROUND: Diffuse esophageal spasm (DES) is characterized on manometry by a combination of simultaneous contractions and normal swallows. The aim of this study was to examine the manometric characteristics of simultaneous and 'normal' swallows in patients with DES patients compared with normal controls. METHODS: Manometric studies from 69 patients with DES and 20 controls were analysed to determine the proportion of normal, hypertensive, ineffective and simultaneous contractions, and the velocity of propagation along the esophagus, the duration and amplitude of contraction and the relaxation characteristics (nadir and duration) of the lower esophageal sphincter. KEY RESULTS: The propagation velocity was the only significant difference between normal swallows and simultaneous contractions in DES patients (middle third: 49.2 VS 101.2 mm s(-1), P ≤ 0.001 lower third: 44.1 VS 88.7 mm s(-1), P ≤ 0.001). 'Normal' swallows in patients with DES had a greater velocity of propagation than those in age-matched control subjects (middle third: 49.2 VS 37.0 mm s(-1), P = 0.02, lower third: 44.1 VS 23.3 mm s(-1), P ≤ 0.001). CONCLUSIONS & INFERENCES: As expected, simultaneous contractions of DES patients differ from 'normal' swallows in DES patients mainly regarding the velocity of propagation of contraction but are similar in amplitude, however 'normal' swallows of DES patients are also more rapidly propagated along the esophagus than normal swallows of a control group suggesting that all swallows in DES are affected to some degree by the same process.

Is esophageal dysphagia in the extreme elderly (>or=80 years) different to dysphagia younger adults? A clinical motility service audit.

Dysphagia in elderly patients has major effects on nutrition and quality of life. Although aging itself is associated with changes in esophageal motility, the impact of this on symptoms such as dysphagia is unclear. Data in the extreme elderly are also limited. Symptoms and manometric diagnoses from 23 consecutive older patients (older dysphagia [OD]) >or=80 reporting esophageal dysphagia (12 female, mean age 83 (range 80-93) were compared with those from 23 gender matched younger patients (young dysphagia [YD]) also with dysphagia (mean age 35, range [17-46]). More older patients reported dysphagia as their primary symptom (OD 22/23 vs YD 14/23, P = 0.005). Overall, dysphagia was most common for solids only (OD 16/23 vs YD 15/23) and rare for liquids only (OD 1/23 vs YD 3/23). Dysphagia for both liquids and solids was more frequent in older patients (OD 6/23 vs YD 1/23, P < 0.05). Fewer older patients reported heartburn (OD 3/23 vs YD 14/23, P = 0.001). Manometric diagnoses were generally similar between OD and YD patients with the most common diagnoses being 'nonspecific esophageal motility disorder' (nine each) and 'ineffective peristalsis' (OD = 6, YD = 7). There was a trend for diagnoses related to lower esophageal sphincter failure to be more frequent in younger subjects (OD 1 vs YD 7, P = 0.053). Despite differences in symptom patterns, broad manometric diagnoses in the extreme elderly with dysphagia are similar to younger dysphagia patients. Further studies are required to determine whether this relates to insensitivity in recording or reporting of esophageal manometry (or perceptual differences associated with aging).

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.

Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse.

BACKGROUND AND AIMS: To explore the association between chronic cannabis abuse and a cyclical vomiting illness that presented in a series of cases in South Australia. METHODS: Nineteen patients were identified with chronic cannabis abuse and a cyclical vomiting illness. For legal and ethical reasons, all patients were counselled to cease all cannabis abuse. Follow up was provided with serial urine drug screen analysis and regular clinical consultation to chart the clinical course. Of the 19 patients, five refused consent and were lost to follow up and five were excluded on the basis of confounders. The remaining nine cases are presented here and compared with a published case of psychogenic vomiting. RESULTS: In all cases, including the published case, chronic cannabis abuse predated the onset of the cyclical vomiting illness. Cessation of cannabis abuse led to cessation of the cyclical vomiting illness in seven cases. Three cases, including the published case, did not abstain and continued to have recurrent episodes of vomiting. Three cases rechallenged themselves after a period of abstinence and suffered a return to illness. Two of these cases abstained again, and became and remain well. The third case did not and remains ill. A novel finding was that nine of the 10 patients, including the previously published case, displayed an abnormal washing behaviour during episodes of active illness. CONCLUSIONS: We conclude that chronic cannabis abuse was the cause of the cyclical vomiting illness in all cases, including the previously described case of psychogenic vomiting.

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.