Determinants of venom-specific IgE antibody concentration during long-term wasp venom immunotherapy

Background: Venom immunotherapy (VIT) is an effective treatment for subjects with systemic allergic reactions (SR) to Hymenoptera stings, however there are few studies concerning the relevance of the venom specific IgE changes to decide about VIT cessation. We assessed IgE changes during a 5-year VIT, in patients stung and protected within the first 3 years (SP 0-3) or in the last 2 years (SP 3-5), and in patients not stung (NoS), to evaluate possible correlations between IgE changes and clinical protection. Methods: Yellow jacket venom (YJV)-allergic patients who completed 5 years of VIT were retrospectively evaluated. Baseline IgE levels and after the 3rd and the 5th year of VIT were determined; all patients were asked about field stings and SRs. Results: A total of 232 YJV-allergic patients were included and divided into the following groups: 84 NoS, 72 SP 0-3 and 76 SP 3-5. IgE levels decreased during VIT compared to baseline values (\u3c72 = 346.029, p < 0.001). Recent vespid stings accounted for significantly higher IgE levels despite clinical protection. IgE levels after 5 years of VIT correlated significantly with Mueller grade (F = 2.778, p = 0.012) and age (F = 6.672, p = 0.002). During follow-up from 1 to 10 years after VIT discontinuation, 35.2 % of the contacted patients reported at least one field sting without SR. Conclusions: The yellow jacket-VIT temporal stopping criterion of 5 years duration did not result in undetectable IgE levels, despite a long-lasting protection. A mean IgE decrease from 58 to 70 % was observed, and it was less marked in elderly patients or in subjects with higher Mueller grade SR

Tryptase as a marker of severity of aortic valve stenosis

Background: Severe aortic valve stenosis is one of the most common cause of mortality in adult patients affected with metabolic syndrome, a condition associated with an active inflammatory process involving also mast cells and their mediators, in particular tryptase. The aim of this study was to characterize the possible long-term prognostic role of tryptase in severe aortic valve stenosis. Case presentation: The baseline serum tryptase was measured in 5 consecutive patients admitted to our Hospital to undergo aortic valve replacement for severe acquired stenosis. Within 2years after, the patients were evaluated for the occurrence of major cardiovascular events (MACE). The tryptase measurements were higher in patients experiencing MACE (10.9, 11.7 and 9.32ng/ml) than in non-MACE ones (5.69 and 5.58ng/ml). Conclusions: In patients affected with severe aortic stenosis, baseline serum tryptase may predict occurence of MACE. Further studies are needed to demonstrate the long-term prognostic role of this biomarker

Identification and molecular characterization of allergenic nsLTP from durum wheat (Triticum turgidum)

Background: Common wheat (Triticum aestivum) and durum wheat (T. turgidum) are both involved in Baker's asthma (BA) and food allergy (FA) including wheat-dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have not been described, and the over-expression of T. turgidum non-specific lipid-transfer protein (nsLTPs) is considered to increase resistance to phytopathogens. Objective: To identify and assess the allergenicity of nsLTP from T. turgidum. Methods: Recombinant T. turgidum nsLTP Tri tu 14 was generated and tested for structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE). Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with positive bronchial challenge to wheat flour, and 12 Italian patients (wheat FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T. aestivum) and Pru p 3 (P. persica) were determined by ImmunoCAP testing. Allergenic potency (in vitro mediator release) and IgE cross-reactivity were investigated. Results: Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The correlation between Tri a 14 and Tri tu 14 specific IgE levels was r = 0.97 (BA) and r = 0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed allergenic activity by mediator release from effector cells and IgE cross-reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat nsLTPs varied between individual patients. Conclusions and Clinical Relevance: Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for patients with nsLTP-mediated FA

Tolerated drugs in subjects with severe cutaneous adverse reactions (SCARs) induced by anticonvulsants and review of the literature

Background: Anticonvulsant hypersensitivity syndrome represents a rare but potentially fatal kind of adverse drug reaction. This clinical picture often hampers the flexibility with which alternative anticonvulsants or even other classes of drugs are prescribed in these patients, negatively affecting the efficacy of treatment and the course of the disease. The aim of this study was to analyse a group of six patients with severe cutaneous drug reactions induced by anticonvulsants and to report which alternative antiepileptic drugs and which drugs of other classes were tolerated. Case presentation: A total of six patients (2 males and 4 females, age 11-73 years) are described in this study. In all the patients the onset of the severe cutaneous drug reactions was 2-4 weeks after initiating the anticonvulsant therapy: 2 out of 6 patients presented with a drug reaction with eosinophilia and systemic symptoms under therapy with phenytoin; 2 out of 6 presented with Stevens-Johnson syndrome under therapy with lamotrigine; and 2 out of 6 presented with a toxic epidermal necrolysis, one of them under therapy with valproic acid, and the other one under therapy with lamotrigine. Alternative anticonvulsants tolerated after the reaction were: clonazepam, levetiracetam, diazepam, delorazepam and lormetazepam. Conclusions: In our cases we observed that non aromatic anticonvulsants and benzodiazepines were well tolerated as alternative treatments in six patients with reactions to aromatic anticonvulsivants and that the risk of hypersensitivity reactions to other drug classes was not increased as compared to general population

Mast cells and acute coronary syndromes : Relationship between serum tryptase, clinical outcome and severity of coronary artery disease

Objective: To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year followup in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score). Methods: We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2 years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score. Results: Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7 ng/mL (sensitivity 46%, specificity 84%). Conclusions: In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker

Identification of risk factors of severe hypersensitivity reactions in general anaesthesia

Background: Hypersensitivity reactions to anaesthetic agents are rare but often severe, with a mortality ranging from 4 to 9% in IgE-mediated events. Identification of the risk factors may contribute to limit the incidence of these reactions. The aim of our study was to search for possible risk factors of severe perioperative hypersensitivity reactions in our study population. Methods: For this study we retrospectively reviewed data from 193 patients who experienced drug hypersensitivity reactions during general anaesthesia. The diagnostic protocol consisted of 1) history of the reaction, 2) measurement of serum baseline tryptase and specific IgE-assays for latex, beta-lactams and succinylcholine, 3) skin tests for the agents listed in the anaesthesia chart and for others likely to be safe for future use, latex, and others medications administered during the perioperative period (i.e. antibiotics), 4) subdivision of our patients on the basis of two criteria: a) grade of severity of clinical reactions according to the Ring and Messmer classification; b) results of skin tests and/or serum specific IgE-assays. Results: One hundred of 193 patients had reactions of grade I, 32/193 patients had reactions of grade II, 55/193 patients had reactions of grade III and 6/193 patients had reactions of grade IV. A diagnosis of IgE-mediated reaction was established in 55 cases (28.50%); the most common causes were neuromuscular blocking agents, followed by latex and beta-lactams. Severe reactions were associated with older age (p = 0.025), asthma (p = 0.042), history of hypertension (p = 0.001), intake of serum angiotensin converting enzyme inhibitor medication (p = 0.012) or serum angiotensin II antagonist (p = 0.033), higher levels of basal tryptase (p = 0.0211). Cardiovascular symptoms (p = 0.006) and history of hypersensitivity to antibiotics (p = 0.029) were more frequently reported in IgE-mediated reactions. Conclusions: We confirmed the relevance of several clinical features as risk factors for anaphylactic reactions induced by anaesthetic agents: older age, asthma, hypertension and antihypertensive drugs. We observed increased levels of serum basal tryptase in severe reactions: this finding may signify that this biomarker is useful for the identification of patients at risk

5-grass pollen tablets achieve disease control in patients with seasonal allergic rhinitis unresponsive to drugs : a real-life study

BACKGROUND: An important subpopulation in allergic rhinitis is represented by patients with severe form of disease that is not responsive to drug treatment. It has been reported that grass pollen subcutaneous immunotherapy is effective in drug-resistant patients. In a real-life study, we evaluated the efficacy of 5-grass pollen tablets in patients with grass pollen-induced allergic rhinitis not responsive to drug therapy. METHODS: We carried out this multicenter observational study in adults and adolescents with grass-induced allergic rhinitis not responsive to drug therapy who were treated for a year with 5-grass pollen tablets. Clinical data collected before and after sublingual immunotherapy (SLIT) included Allergic Rhinitis and its Impact on Asthma (ARIA) classification of allergic rhinitis, response to therapy, and patient satisfaction. RESULTS: Forty-seven patients entered the study. By ARIA classification, three patients had moderate to severe intermittent allergic rhinitis, ten had mild persistent allergic rhinitis, and 34 had moderate to severe persistent allergic rhinitis. There were no cases of mild intermittent allergic rhinitis before SLIT. After SLIT, 33 patients had mild intermittent allergic rhinitis, none had moderate to severe intermittent allergic rhinitis, seven had mild persistent allergic rhinitis, and seven had moderate to severe persistent allergic rhinitis. The mean medication score decreased from 4.2\ub11.3 before to 2.4\ub12.0 after SLIT (P<0.01), representing a reduction of 42%. The response to treatment before SLIT was judged as poor by 70% of patients and very poor by 30%. Patient satisfaction was significantly increased after SLIT (P<0.01). CONCLUSION: In real life, most patients with grass pollen-induced allergic rhinitis not responsive to drug treatment can achieve control of the condition with one season of treatment using 5-grass pollen tablets. KEYWORDS: allergen immunotherapy, drug resistance, effectiveness, grass pollen, patient satisfaction, rhiniti

A population of highly energetic transient events in the centres of active galaxies

Recent all-sky surveys have led to the discovery of new types of transients. These include stars disrupted by the central supermassive black hole, and supernovae that are 10–100 times more energetic than typical ones. However, the nature of even more energetic transients that apparently occur in the innermost regions of their host galaxies is hotly debated1,2,3. Here we report the discovery of the most energetic of these to date: PS1-10adi, with a total radiated energy of ~2.3 × 1052 erg. The slow evolution of its light curve and persistently narrow spectral lines over ∼ 3 yr are inconsistent with known types of recurring black hole variability. The observed properties imply powering by shock interaction between expanding material and large quantities of surrounding dense matter. Plausible sources of this expanding material are a star that has been tidally disrupted by the central black hole, or a supernova. Both could satisfy the energy budget. For the former, we would be forced to invoke a new and hitherto unseen variant of a tidally disrupted star, while a supernova origin relies principally on environmental effects resulting from its nuclear location. Remarkably, we also discover that PS1-10adi is not an isolated case. We therefore surmise that this new population of transients has previously been overlooked due to incorrect association with underlying central black hole activity