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Background and objective Wheat ingestion can lead to disorders such as IgE-mediated food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA), both of which are associated with impaired quality of life and significant morbidity. Allergy to wheat is relatively benign in children, although its natural history in adults is still unknown. Objective: We used placebo-controlled challenge to evaluate the natural history of wheat hypersensitivity in atopic patients with adultonset wheat allergy. Methods We enrolled 13 patients from an initial cohort of adult patients with IgE-mediated wheat allergy (mean age, 40 years). After diagnosis, the patients observed a wheat-free diet and were followed as outpatients for 5 years to evaluate wheat exposure. Wheat-IgEtiters were determined at the end of follow-up, and a second wheat-challenge was performed. Results Ten out of 13 patients took part in the study. The mean period of wheat avoidance was 4.2 years. Three patients had spontaneously reintroduced wheat before the second evaluation, after a mean (IQR) of 28 (18-36) months, with only mild gastrointestinal discomfort at reintroduction. At the end of follow-up, 9 of the 10 patients were wheat-tolerant. Two patients had a history of WDEIA. We observed a reduction in IgE levels, with median (IQR) IgE falling from 2.77 (0.35-100) kU/L at diagnosis to 0.88 (0.1-20.8) kU/L. The association between IgE and a negative challenge result was not statistically significant. Conclusion IgE-mediated wheat allergy in adults is benign and represents a temporary break in gastrointestinal tolerance. Future studies may improve our knowledge of wheat allergens, routes of and factors leading to sensitization, and prognostic biomarkers.

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.

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.

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 2 years 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 9.32 ng/ml) than in non-MACE ones (5.69 and 5.58 ng/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.

We describe the case of a patient that developed persistent severe asthma after having started to work in a bakery. The subsequent appearance of gastrointestinal symptoms was diagnosed as celiac disease (CD). She also experienced severe asthma attacks when cooking pasta, and expe-rienced anaphylactic shock a few minutes after wheat flour inhalation. The allergologic workup was positive for several cereal products and Tri a 14 (Tricum aestivum 14), while specific IgE titer to Pru p 3 (Prunus persica 3) was negative. Our patient had no recurrence of these episodes when she avoided cooking wheat flour products and wheat in processed foods. The pathogenic mechanisms underlying CD and IgE-mediated food allergy are different and the coexistence of both diseases seems to be rare. Tri a 14 is the major wheat allergen involved in our case; this allergen can sensitize through the respiratory and the oral route, and can give way to anaphylaxis. A possible role played by interleukin-15 (IL-15) and interleukin-21 (IL-21) in the induction of IgE-mediate hypersensitivity, as well as in the pathogenesis of CD, is prospected and discussed briefly herein.

Background: β-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 β-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.

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.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12948-015-0017-9) contains supplementary material, which is available to authorized users.

Summary Background The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. Objective We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. Methods Thirty-two patients (18 M/14 F, mean age 36.78, range 23–60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 μg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. Results Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P

The aim of this study was to assess the ability of nedocromil sodium (NS) to prevent the immediate asthmatic reaction and the increase in the serum level of heat stable neutrophil chemotactic activity (HS-NCA) induced by antigen inhalation. In a double-blind, cross-over study, 13 atopic subjects affected with seasonal asthma underwent a bronchial provocation test with a preselected dose of grass pollen allergen (enough to cause a decrease of > or = 20% in FEV1:FEV1 PD20) after pre-treatment with 4 mg NS or placebo. Serum samples were withdrawn from 11 subjects for HS-NCA determination. After NS administration the decrease in FEV1 was significantly less than after placebo administration at all time points after challenge (2 min P = 0.0004; 7 min, P = 0.0005; 17 min P = 0.0002 and 27 min P = 0.0005). The percentage increase in HS-NCA was significantly higher after placebo than after NS inhalation, both 10 (P = 0.0048) and 20 (P = 0.0068) min after challenge. Our study confirms previous investigations, showing that NS inhibits the immediate asthmatic response to allergen inhalation in atopic, asthmatic subjects and moreover it shows that this drug prevents in vivo the increase of the serum HS-NCA. This last finding has not been previously reported.

Objective A group of 148 peach allergic patients, recruited in a ongoing clinical study (Clinical Trials.gov, protocol ID NCT00715156) aimed at studying the relationship between the clinical manifestations to peach and the positivity to different peach major allergens (Pru p 3, 1 and 4), were divided into 2 groups according to peach induced symptoms: group A (mild-OAS; 76 pts) and group B (severe-OAS with systemic symptoms, 72 pts). These patients were examined to see if severe allergic symptoms to peach were a risk factor for developing severe symptoms to other plant foods allergens.

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening cutaneous severe adverse reactions (SCAR) most frequently induced by a drug hypersensitivity. The clinical manifestations seem to be related either to a particular group of drugs, such as antibacterial sulfonamides, anticonvulsant agents, allopurinol, non-steroidal anti-inflammatory drugs (NSAIDs), aminopenicillins and quinolones, as well as to the ethnic/genetic background of the affected individual. A relevant problem in these subjects is the selection of a potentially tolerated drug that is less likely to induce a relapse of the reaction on the basis of cross-reactivity. Aim of the present study was to analyse a population of 16 patients that were treated in the burn/intensive care department for a SJS/TEN reaction, and determine the drugs that were tolerated after the reaction with respect to the culprit substances. The diagnosis was performed on the basis of the clinical and histological features according to the RegiSCAR classification and the first step was withdrawal of the offending drug. Among the 16 cases, we found 5 cases of SJS, 8 cases of TEN, and 3 cases of SJS/ TEN overlap. Of the 16, 4 patients were male and 12 were female, age 14-92 years (average 57.1 years; median 63.5 years). A total of 12 drugs were found as suspected causative agents. In 3 cases multiple drugs were suspected, whereas in 13 cases a single drug was implicated. Antimicrobials including amoxicillin, levofloxacin, trimethoprimsulfamethoxazole, vancomycin (8/16; 50 %) were the most commonly associated agents followed by antiseizure drugs (4/16; 25 %), NSAIDs (3/16; 18.75 %), benzodiazepines (2/16; 12.5 %) and allopurinol (1/16; 6.25 %). The most common complications noted were secondary infections (15/16; 93.75 %) and septicemia (11/16; 68.75 %). Mortality rate was 18,75 % (3/16). Interestingly patients with reactions to quinolones tolerated glycopeptides and carbapenems. Also, a patient with reaction to amoxicillin tolerated carbapenems. One of the 4 patients with reaction to anticonvulsant tolerated levetiracetam, 4/4 benzodiazepines, and 1/4 haloperidol. A patient with suspected reaction to acetaminophen (amoxicillin was the other involved drug) tolerated nimesulide and carbapenems. A patient with reaction to oxcarbazepine tolerated diazepam. We conclude that a competent burn centre staff can guarantee the successful management of the patients.