In a patient presenting with acute angioedema, a raised serum mast-cell tryptase level may at first suggest an allergic cause. Persistent tryptase elevation may indicate a mast cell disorder. In this case, the raised tryptase turned out to be incidental to the final diagnosis, which was acquired C1 inhibitor deficiency caused by a B-cell lymphoma. We believe this is the first report of elevated tryptase in association with B-cell lymphoid malignancy and acquired angioedema.

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).

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.

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.

Summary 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.

RATIONALE: To analyze NSAID-induced acute cutaneous and anaphylactic reactions through a structured approach to oral drug challenges. METHODS: Retrospective analysis of the drug challenge results of all patients with NSAID-induced urticaria, angioedema or anaphylaxis presenting between February 2006 and June 2010. Oral drug challenges followed a structured protocol and were either homologous to confirm diagnosis or heterologous to explore cross-reactivity. RESULTS: 68 patients (53 females, 15 males, mean age 48.3) reported a total of 77 instances of defined NSAID-induced reactions of which 62% were cutaneous and 35% systemic anaphylaxes. Ibuprofen was most commonly incriminated NSAID (35%) whereas most cases of anaphylaxis were related to diclofenac (48%). 92% of anaphylactic reactions occurred with NSAID use for acute pain. 40 patients underwent a homologous challenge of which 17 were positive. Presentation with anaphylaxis, shorter reaction-to-challenge time and challenge with diclofenac were main predictors of a positive challenge. 28 patients had a challenge with heterologous NSAID, including 21 aspirin challenges (7 positive). Overall structured challenges enabled us to identify 23 (34%) selective Reactors (SR), 19 (28%) Cross Reactors (CR) and 23 (34%) NSAID-tolerant patients. SR presented most often with anaphylaxis and were otherwise healthy except for some with a background of B-lactam allergy. CR in contrast often had a background of chronic urticaria or asthma and presented with milder cutaneous reactions especially isolated periorbital angioedema. CONCLUSION: A structured approach to drug challenges allows identification of Selective and Multiple NSAID hypersensitivity syndromes. Most patients with NSAID-induced anaphylaxis are SR and hence do not require avoiding other NSAID.

Internal Medicine JournalVolume 32, Issue 5-6 p. 271-272 Failure of montelukast to prevent aspirin-induced asthma A. Broadfoot, A. Broadfoot Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this authorD. Gillis, D. Gillis Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this authorR. Heddle, R. Heddle Department of Immunology, Allergy, and Arthritis, Flinders Medical Centre, Adelaide, South Australia, AustraliaSearch for more papers by this authorW. Smith, W. Smith Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this authorF. Kette, F. Kette Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this author A. Broadfoot, A. Broadfoot Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this authorD. Gillis, D. Gillis Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this authorR. Heddle, R. Heddle Department of Immunology, Allergy, and Arthritis, Flinders Medical Centre, Adelaide, South Australia, AustraliaSearch for more papers by this authorW. Smith, W. Smith Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this authorF. Kette, F. Kette Department of Clinical Immunology and Allergy, Royal Adelaide Hospital andSearch for more papers by this author First published: 27 May 2002 https://doi.org/10.1046/j.1445-5994.2002.00209.xCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume32, Issue5-6May/June 2002Pages 271-272 RelatedInformation

Australian and New Zealand Journal of MedicineVolume 25, Issue 6 p. 741-741 Common variable immunodeficiency associated with nodular regenerative hyperplasia of the liver J. RAVINDRAN, J. RAVINDRAN Immunology ResidentSearch for more papers by this authorD. GILLIS, D. GILLIS Specialist ImmunologistSearch for more papers by this authorR. ROWLAND, R. ROWLAND Senior Director Tissue PathologySearch for more papers by this authorR. HEDDLE, R. HEDDLE Specialist in Clinical Immunology (including Allergy) Institute of Medical and Veterinary Science, Adelaide, SA.Search for more papers by this author J. RAVINDRAN, J. RAVINDRAN Immunology ResidentSearch for more papers by this authorD. GILLIS, D. GILLIS Specialist ImmunologistSearch for more papers by this authorR. ROWLAND, R. ROWLAND Senior Director Tissue PathologySearch for more papers by this authorR. HEDDLE, R. HEDDLE Specialist in Clinical Immunology (including Allergy) Institute of Medical and Veterinary Science, Adelaide, SA.Search for more papers by this author First published: December 1995 https://doi.org/10.1111/j.1445-5994.1995.tb02867.xCitations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume25, Issue6December 1995Pages 741-741 RelatedInformation