The Severity and Frequency of Systemic Reactions to Hazelnut Are Significantly Higher in Hazelnut Allergic Patients Monosensitized to Cor a 8 than in Patients Polysensitized to Cor a 1, Cor a 8, and Cor a 9.

INTRODUCTION: Hazelnuts are a leading trigger of food allergy. To date, several molecular components of hazelnut are available for component-resolved diagnosis. However, little is known about how simultaneous sensitization to multiple allergens affects the severity of the hazelnut-induced reaction. In a previous study, our group demonstrated a lower risk of systemic reactions to peach in patients sensitized to both Pru p 3 and Pru p 1 than in the patient monosensitized to peach LTP. We aimed to assess whether this was also true in hazelnut allergy in a cohort of adult patients. METHODS: Patients were selected based on a history of symptoms such as urticaria, vomiting, diarrhea, asthma, and anaphylaxis indicative of hazelnut IgE-mediated food allergy and graded according to a clinical severity scale. For all patients, specific IgE was determined for Cor a 1 and Cor a 8 and, for most patients, also Cor a 9. Patients were offered an oral food challenge in open format (OFC) with a cocoa-based roasted hazelnut spread on a voluntary basis in order to prescribe an appropriate diet. RESULTS: A total of two hundred and fourteen patients were recruited. Among these, 43 patients were monosensitized to Cor a 8. One hundred and seventy-one patients were sensitized to Cor a 1 (79.9%), and, among them, 48/171 (28.1%) were also Cor a 8 positive. Cor a 9 was evaluated in 124/214 patients, testing positive in 21/124 (16.9%). Patients monosensitized to Cor a 8 experienced systemic reactions more frequently than those sensitized to Cor a 1 ± Cor a 8 (p < 0.00001), with significantly more severe reactions (p < 0.0005) and testing more frequently positive at OFC (p < 0.0001). Regarding Cor a 9, the sensitized patients were significantly younger (p = 0.0013) and showed reactions of similar severity to patients who tested Cor a 9 negative, and these reactions were milder than in patients monosensitized only to Cor a 8. DISCUSSION/CONCLUSION: Sensitization to Cor a 1 seems to protect from the development of the severe systemic reactions induced by Cor a 8 sensitization, Cor a 9 does not influence the severity of symptoms in adult patients. The OFC with roasted hazelnut may help in dietary guidance.

Diagnostic management of patients reporting symptoms after wheat ingestion.

Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.

Switching from one biologic to benralizumab in patients with severe eosinophilic asthma: An ANANKE study post hoc analysis.

Background: Severe asthma is a heterogeneous inflammatory disease driven by eosinophilic inflammation in the majority of cases. Despite biologic therapy patients may still be sub-optimally controlled, and the choice of the best biologic is a matter of debate. Indeed, switching between biologics is common, but no official guidelines are available and real-world data are limited. Materials and methods: In this post hoc analysis of the Italian, multi-center, observational, retrospective study, ANANKE. Patients with severe eosinophilic asthma treated with benralizumab were divided in two groups based on history of previous biologic therapy (biologic-experienced [suboptimal response] vs naïve). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment. Change over time in blood eosinophils, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use following benralizumab initiation were collected in the two groups. Results: A total of 147 biologic-naïve and 58 biologic-experienced (34 omalizumab, 19 mepolizumab, and 5 omalizumab-mepolizumab) patients were enrolled. Biologic-experienced patients were more likely to be atopic and have a higher AER despite more frequent OCS use. Similar reductions in AER (>90% in both groups), OCS use (≥49% reduction in dosage and ≥41% able to eliminate OCS), ACT improvement (≥7 points gained in 48 weeks) and lung function (≥300 mL of FEV1 improvement in 48 weeks) were observed after benralizumab introduction within the two groups. There were no registered discontinuations of benralizumab for safety reasons. Conclusion: In this post hoc analysis, patients who were switched to benralizumab because of suboptimal control with a previous biologic therapy were more likely to be atopic and more often treated with omalizumab. Benralizumab is effective in both naïve patients and those previously treated with a biologic.

Mollusk allergy in shrimp-allergic patients: Still a complex diagnosis. An Italian real-life cross-sectional multicenter study.

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly. Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods. Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro. Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p < 0.001), also using fresh cooked or raw food (p < 0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to tolerant subjects, but 33% of patients were not detected by any of the available molecules. Overall, a higher frequency of IgE rectivity to shrimp was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south. Conclusion: The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity should still rely on skin tests with fresh material. The exclusion of mollusks from shrimp allergic patients' diets should occur when clinical history, available diagnostic instruments, and/or tolerance tests support such a decision.

Benralizumab in Patients With Severe Eosinophilic Asthma With and Without Chronic Rhinosinusitis With Nasal Polyps: An ANANKE Study post-hoc Analysis.

Background: Severe eosinophilic asthma (SEA) in the presence of chronic rhinosinusitis with nasal polyps (CRSwNP) indicates the presence of a more extensive eosinophilic inflammation. Post-hoc analyses from a pivotal clinical trial have demonstrated the enhanced efficacy of benralizumab on asthma outcomes in patients with CRSwNP as a comorbidity. Methods: This is a post-hoc analysis from the Italian multi-center observational retrospective ANANKE study. Patients were divided into two groups based on self-reported CRSwNP. Baseline clinical and laboratory features in the 12 months prior to benralizumab prescription were collected. Data of change over time of blood eosinophils, annualized exacerbations rates (AER), asthma control, lung function, oral corticosteroids (OCS) use, and benralizumab discontinuation were collected during the observation period. Results: At baseline, the 110 patients with CRSwNP were less frequently female (50.9% vs 74.2%) and obese (9.1% vs. 22.6%) with higher eosinophils (605 vs. 500 cells/mm3) and OCS use when compared to patients without CRSwNP. Similar reductions of AER were seen (-95.8% vs. -91.5% for any exacerbation and -99.1% vs. -92.2% for severe exacerbations in patients with and without CRSwNP, respectively). During benralizumab treatment, comorbid SEA+CRSwNP was associated with a lower risk of any exacerbation (p = 0.0017) and severe exacerbations (p = 0.025). After a mean ± SD exposure of 10.3 ± 5.0 months, half of the SEA+CRSwNP patients eliminated OCS use. No discontinuation for safety reasons was recorded. Conclusions: This study helped to confirm the baseline clinical features that distinguish patients with and without CRSwNP being prescribed benralizumab. Numerically enhanced OCS reduction and lower exacerbation risk were observed in patients with SEA and comorbid CRSwNP treated with benralizumab.

ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study.

BACKGROUND: Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. METHODS: ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. RESULTS: Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. CONCLUSIONS: We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463.

Clinical Features of Wheat Allergy Are Significantly Different between Tri a 14 Sensitized Patients and Tri a 19 Sensitized Ones.

INTRODUCTION: Wheat is the most important cereal for human nutrition but its high consumption is associated to an increasing complaint of wheat-related disorders, many of which are allergic in nature and different in respect to the involved allergens. In this study, we compared the clinical aspects of wheat allergy presented by patients sensitized to Tri a 19 in respect to those presented by patients sensitized to Tri a 14. METHODS: With this aim, we selected patients sensitized to 1 or both of the 2 allergens, and among these we identified those who were really wheat allergic and reactive on the basis of a standardized methodology. We evaluated the clinical features such as the kind and severity of symptoms, the coexistence of triggering factors such as physical exercise and NSAIDs and alcohol consumption, and the association with other allergens and with various immunologic parameters. Wheat allergy in Tri a 19 sensitized patients was confirmed through a questionnaire while the patients sensitized to Tri a 14 underwent wheat challenge with 100 g of pasta followed by exercise on a treadmill. RESULTS: Seventy-nine patients sensitized to Tri a 14 and 40 patients sensitized to Tri a 19 were recruited. The 2 sensitizations were independent with a significant inverse relation (p < 0.00001). The Tri a 19 sensitized patients presented, in respect to the Tri a 14 sensitized ones, an older age (p = 0.0017), a higher risk to be wheat allergic (p < 0.0001), a higher severity of the reactions (p < 0.00001) and a higher association with some cofactors, namely alcohol (p < 0.0005) and physical exercise (p = 0.003). On the contrary, Tri a 14 sensitization was associated with atopy (p < 0.0001), with a higher probability of patients being asymptomatic (p < 0.0001) and being sensitized to other foods, in particular to nuts and cereals (p < 0.00001). CONCLUSIONS: Sensitization to Tri a 19 or Tri a 14 determines different clinical pictures. In particular, sensitization to Tri a 19 implies a higher probability of severe reactions, even dependent on daily triggers, while that to Tri a 14 implies a higher cross-reactivity with other foods but it's more frequently asymptomatic, making a food challenge necessary to prevent useless food avoidance.

Role of Multiple Comorbidities and Therapies in Conditioning the Clinical Severity of DRESS: A Mono-Center Retrospective Study of 25 Cases.

DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p=0.0067) and an age of at least 68 years (p=0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.

Basal Tryptase High Levels Associated with a History of Arterial Hypertension and Hypercholesterolemia Represent Risk Factors for Severe Anaphylaxis in Hymenoptera Venom-Allergic Subjects over 50 Years Old.

INTRODUCTION: Allergy to Hymenoptera venom (HV) may lead to life-threatening anaphylaxis. Some of the factors influencing the symptom's severity are still undetermined. The aim of this study was to identify the clinical aspects associated with the most severe reactions in a population with HV allergy, by comparing clinical and immunochemical biomarkers between patients with previous local large reactions (LLRs) and systemic reactions (SRs). METHODS: We selected adult patients with a history of HV allergy, with positive diagnostic tests and a correlation with one single Hymenoptera species. Age, gender, atopy, serum basal tryptase (sBT) value, total IgE, venom-specific IgE, history of hypertension, cardiovascular diseases, and hypercholesterolemia were compared between patients with previous LLRs and SRs. RESULTS: 460 adult patients (381 SRs, 79 LLRs) were included. Age (p = 0.0097), male gender (p < 0.0001), arterial hypertension (p = 0.046), hypercholesterolemia (p = 0.009), and higher sBT levels (p = 0.0004) were significantly associated with severe reactions as independent variables. Moreover, considering the previous variables as risk factors, there was a significant and progressive increase in the odds of being Mueller III + IV as the number of positive variables increased. Patients with sBT ≥6.4 ng/mL adjusted for any of the positive variables had increased the risk of Mueller grade IV reaction (p < 0.0001). CONCLUSION: According to our results, older age, male gender, arterial hypertension, hypercholesterolemia, and increased levels of sBT ≥6.4 ng/mL are risk factors for severe anaphylaxis to HV in adults. Atopy and allergic asthma do not increase the risk of HV-induced SRs.

Socio-economic burden and resource utilisation in Italian patients with chronic urticaria: 2-year data from the AWARE study.

INTRODUCTION: In Italy, the real-world evidence on the extent of adherence to guidelines and the benefits of recommended therapeutic medications and their impact on the quality of life (QoL) of H1-antihistamines (H1-AH) refractory chronic urticaria (CU) patients is limited. METHODS: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) was a global prospective, non-interventional study of CU in real-world setting which included patients aged ≥18 years with a medically confirmed diagnosed of CU present for more than 2 months. In this study, the disease characteristics, pharmacological treatments and patient-reported outcomes (PROs) are reported. RESULTS: In total, 159 patients from 24 study centres in Italy completed the study. At baseline, 221 (89.5%) and 8 (3.2%) patients had chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), respectively, while 18 (7.3%) patients had concomitant CSU and CIndU. For CSU patients, mean dermatology life quality index and CU quality of life questionnaire scores reduced to 3.0 ± 4.9 and 14.6 ± 18.6 at Month 24 from baseline scores of 7.5 ± 6.6 and 33.2 ± 19.5, respectively, indicating an improvement in QoL. This was reflected in their work-life as work productivity impairment reduced considerably after 2 years. Only 71.9% CSU patients had a prior treatment, while during the study, 96.8% of the patients were treated with a medication. At baseline, only 52.9% CSU patients reported nonsedating H1-antihistamines as first-line of treatment in prior medication, this increased to 89.6% during current medication. CONCLUSION: This study shows that CSU has a considerable socio-economic burden and an improvement in QoL can be achieved in CSU patients if an appropriate therapeutic path is followed.

Omalizumab Use in Chronic Spontaneous Urticaria during Pregnancy and a Four Years' Follow-Up: A Case Report.

Chronic spontaneous urticaria (CSU) is a benign skin disorder usually responsive to treatment; however, at times it can be difficult to control and become very debilitating. We discuss the case of a woman with CSU that was unresponsive to H1-antihistamines who was treated with omalizumab and became pregnant during omalizumab treatment. We also considered the follow-up of the mother and newborn for 4 years after delivery. Our case report confirms that omalizumab is a safe and effective therapeutic option, after careful evaluations in terms of cost-effectiveness, in pregnant and lactating women with severe chronic urticaria. Assessment throughout follow-up confirmed a regular progression of pregnancy parameters and no adverse reaction was documented in the child from birth to 4 years of age.

Anti-Neutrophil Cytoplasmic Antibodies Positivity and Anti-Leukotrienes in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Monocentric Study on 134 Italian Patients.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. OBJECTIVE: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. METHOD: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca' Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. RESULTS: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. CONCLUSION: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects.

Anxiety and Depression Effects During Drug Provocation Test.

BACKGROUND: Drug provocation test (DPT) represents the gold standard for the diagnosis of drug allergy. A DPT can be performed in a single-blind placebo-controlled manner. In anxiety and depressive disorders, patients need to be evaluated to understand the nature of placebo reactions. OBJECTIVE: The aim of this study was to evaluate the psychological profile of patients with reactions to placebo during a DPT. METHODS: We consecutively enrolled patients with suspected drug allergy undergoing a DPT preceded by the administration of the placebo. All patients underwent the Hospital Anxiety and Depression Scale (HADS), a questionnaire aimed to identify anxiety and depression, before the challenge test. RESULTS: A total of 196 patients were enrolled into this study: 8 (4%) patients resulted positive to the DPT, 60 (30.6%) demonstrated anxiety or depression based on the HADS, and 54 had at least 1 placebo reaction during drug provocation. There were statically significant correlations between the positivity of the HADS and the finding of a placebo reaction (Fisher's exact test: P < .001), and between the latter and a history of severe reactions to drug (Fisher's exact test: P < .001). CONCLUSIONS: There is a significant and strong correlation between the loss of psychic equilibrium and the development of a placebo reaction during a DPT. We suggest the use the HADS or other validated questionnaire in clinical practice before a DPT to evaluate the possible psychiatric components.

Mite-Induced Asthma and IgE Levels to Shrimp, Mite, Tropomyosin, Arginine Kinase, and Der p 10 Are the Most Relevant Risk Factors for Challenge-Proven Shrimp Allergy.

BACKGROUND: Shrimp sensitization is common in the general population, but the presence of symptoms is only moderately related to sensitization. A point still at issue is which in vivo and/or in vitro tests (food challenge, component-resolved diagnosis, house dust mite [HDM] sensitization) can help in distinguishing shrimp-allergic subjects from subjects that are sensitized but tolerant. METHODS: The aim of this study was to evaluate the role of IgE to the different shrimp and mite allergens in distinguishing shrimp challenge-positive from challenge-negative patients. Subjects with suspected hypersensitivity reactions to shrimp, positive skin prick tests (SPTs), and/or anti-shrimp IgE were submitted to open and double-blind placebo-controlled food challenges (DBPCFC). Specific IgE to shrimp, mites, and the recombinants rPen a 1, rDer p 1, 2, and 10 were tested using ImmunoCAP-FEIA. IgE immunoblotting was performed to identify the patients' allergenic profiles. RESULTS: In total, 13 out of 51 (25.5%) patients with reported reactions to shrimp were truly shrimp allergic (7 DBPCFC positive and 6 with documented severe reactions). These patients had significantly higher skin test wheal diameters than nonallergic patients, as well as higher levels of IgE to rPen a 1 and rDer p 10. HDM-induced asthma and the simultaneous presence of anti-nDer p 1, 2, and 10 IgE levels increased the risk of true shrimp allergy. CONCLUSION: Food challenge tests are mandatory for the diagnosis of shrimp allergy. Tropomyosin is associated with clinical reactivity. HDM-induced asthma and anti-mite IgE are risk factors for shrimp allergy.

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 follow-up 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.

Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2 years.

BACKGROUND: One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients. METHODS: We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE). The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed. RESULTS: The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42). The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p < 0.0001 and p = 0.006, respectively). Conversely, we found no significant association between MACE and C-reactive protein (CRP), and between MACE and maximum level of high-sensitivity troponin (hs-Tn) values. Among all patients with MACE, 96% belonged to the group that presented with cardiovascular complexity at the beginning of ACS index admission (p < 0.0001). The predictive accuracy of serum tryptase for MACE at follow up set at the cut-off point of 4.95 ng/ml at T0 and of 5.2 ng/ml at T3. Interestingly, patients with both the above cut-off tryptase values at T0 and at T3 presented a 1320% increase in the odds of developing MACE (p < 0.0001). CONCLUSION: In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.

Anti-Amoxicillin Immunoglobulin E, Histamine-2 Receptor Antagonist Therapy and Mast Cell Activation Syndrome Are Risk Factors for Amoxicillin Anaphylaxis.

BACKGROUND: ß-Lactam antibiotics (mainly amoxicillin, AX) are the drugs that most frequently induce systemic drug allergy reactions. OBJECTIVE: We attempted to identify the risk factors associated with systemic reactions to AX. METHODS: All patients who were referred to our department for suspected hypersensitivity reactions to AX over a 6-month period were evaluated for anti-AX immunoglobulin E (IgE) levels and skin-test positivity for ß-lactams. Age, sex, concomitant diseases, therapies, total IgE, serum tryptase levels and signs and symptoms suggesting mast cell activation syndrome (MCAS) were analyzed in relation to the severity of the reaction in accordance with the Mueller classification. RESULTS: Sixty-seven patients were selected: 39 with mild reactions such as cutaneous or gastrointestinal symptoms (grades I and II) and 28 with severe systemic reactions (grades III and IV). Anti-AX IgE levels and total IgE were significantly higher in severe reactions than in mild ones (p < 0.00005, p = 0.0037). Treatment with histamine-2 receptor antagonists (anti-H2) was significantly related to severe reactions (p = 0.007). No significant correlations were found between the severity of the reactions and dyslipidemia or levels of angiotensin-converting enzyme and tryptase. CONCLUSION: Anti-AX IgE levels were the most significant immunological parameter distinguishing patients who presented with severe reactions to AX and those with mild reactions. Higher values of total IgE, the use of gastroprotective drugs and signs and symptoms suggesting an MCAS significantly increased the odds ratio of having a severe reaction. The risk of serious adverse reactions to AX increased in older patients and in males, but this trend was not significant.

Serum tryptase: a new biomarker in patients with acute coronary syndrome?

BACKGROUND: Mast cell tryptase has recently been reported to be involved in atherosclerotic plaque destabilization. However, the results of these reports are conflicting. METHODS: The aim of this study was to characterize the role of tryptase as a prognostic marker of patient cardiovascular complexity in acute coronary syndrome (ACS). Furthermore, its association with an angiographic scoring system [defined by the SYNergy between percutaneous coronary intervention (PCI) with the TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score] was examined. The serum tryptase was measured at admission in 65 consecutive ACS patients and in 35 healthy controls. In the patients with ACS, a composite measure of clinical and angiographic patient cardiovascular complexity was indicated by two of the following: clinical adverse events at hospitalization, at least 2 epicardial coronary arteries involved in the atherosclerotic disease, more than 1 stent implanted or more than 2 coronary artery disease risk factors. RESULTS: The tryptase measurements were lower in patients without the composite measure (p < 0.0005). Linear regression showed a significant relationship between tryptase levels and the SYNTAX score (SX-score). Conversely, high-sensitivity troponin values did not correlate with either the composite outcome or the SX-score. The predictive accuracy of serum tryptase for the composite outcome was set at the cut-off point of 5.22 ng/ml (sensitivity 81% and specificity 95.7%). CONCLUSION: In ACS patients, serum tryptase levels at admission may predict patient cardiovascular complexity more reliably than currently known biomarkers. Further studies are needed to demonstrate the long-term prognostic role of this biomarker in ACS.

Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Investigations meeting current standards are limited for the effect of house dust mite (HDM) allergy immunotherapy in asthmatic patients. OBJECTIVE: This trial investigated the efficacy and safety of a standardized quality (SQ; allergen standardization method proprietary to the trial sponsor) HDM SLIT-tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease. This publication reports the results of the endpoints related to asthma. METHODS: Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were randomized 1:1:1:1 to double-blind daily treatment with one of 3 active doses (1, 3, or 6 SQ-HDM) or placebo. Their use of inhaled corticosteroid (ICS) was standardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control. The primary end point was a reduction in ICS dose from the individual subject's baseline dose after 1 year of treatment. RESULTS: The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 µg (P = .004). Relative mean and median reductions were 42% and 50% for 6 SQ-HDM and 15% and 25% for placebo, respectively. No statistically significant differences were observed for the other assessed asthma parameters, reflecting the intended controlled status of the trial subjects. The most common adverse events were local reactions in the mouth. The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo. CONCLUSION: Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control. All active doses were well tolerated.