Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Recommendations for the Use of Tryptase in the Diagnosis of Anaphylaxis and Clonal Mastcell Disorders.

Summary: Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the molecular characteristics of the enzyme and its biological effects, the genetic basis of its production and the release kinetics. Recommendations for the clinical use of tryptase measurement developed by a task force of Società Italiana di Patologia Clinica e Medicina di Laboratorio and Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri are given on the best procedure for a correct definition of the reference values in relation to the inter-individual variability and to the correct determination of tryptase in blood and other biological liquids, in the diagnosis of anaphylaxis (from drugs, food, insect sting, or idiophatic), death from anaphylaxis (post mortem assessment) and cutaneous or clonal mastcell disorders.

House dust mite allergy and shrimp allergy: a complex interaction.

Summary: Background and Objective. Sensitization and allergy to shrimp among Italian house dust mite allergic patients are not well defined and were investigated in a large multicenter study. Methods. Shrimp sensitization and allergy were assessed in 526 house dust mite (HDM)-allergic patients submitted to the detection of IgE to Der p 10 and 100 atopic control not sensitized to HDM. Results. Shrimp allergy occurred in 9% of patients (vs 0% of 100 atopic controls not sensitized to HDM; p minor 0.001). Shrimp-allergic patients were less frequently hypersensitive to airborne allergens other than HDM than crustacean-tolerant subjects (35% vs 58.8%; p minor 0.005). Only 51% of tropomyosin-sensitized patients had shrimp allergy, and these showed significantly higher Der p 10 IgE levels than shrimp-tolerant ones (mean 22.2 KU/l vs 6.2 KU/l; p minor 0.05). Altogether 53% of shrimp-allergic patients did not react against tropomyosin. Conclusions. Shrimp allergy seems to occur uniquely in association with hypersensitivity to HDM allergens and tropomyosin is the main shrimp allergen but not a major one, at least in Italy. Along with tropomyosin-specific IgE levels, monosensitization to HDM seems to represent a risk factor for the development of shrimp allergy among HDM allergic patients.

Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Clinical approach on challenge and desensitization procedures with aspirin in patients with ischemic heart disease and nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, this study aimed to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. METHODS: Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. RESULTS: Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of nonimmediate cutaneous eruptions, and 17 of bronchospasm related to ASA/nonsteroidal anti-inflammatory drugs (NSAID) intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 subjects underwent desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, seven at doses up to 500 mg, three at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. CONCLUSIONS: In patients with stable CIHD and histories of nonsevere hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization.

Parietaria pollination duration: myth or fact?

Background. Even though the Parietaria pollen season may be rather long, it is commonly thought that Parietaria pollen is a perennial allergen present along the whole year. Objective. This study aimed at investigating the duration of Parietaria pollen season during a 10-year period in Italy, analysing also the annual pollen quantity and the differences among geographical areas. Methods. Pollen count was assessed daily for 10 years. Globally, ten Italian centers measured Parietaria pollen count. Start date, peak date, end date, duration (days), peak value, and seasonal pollen index were evaluated in each center. Results. Ten-year Parietaria pollen count demonstrates that the pollen season usually lasted for 6-7 months in Italy. There are important differences among centres, mainly attributable to geoclimatic factors. Conclusion. This study demonstrates that Parietaria pollen season lasts about 6-7 months with two peaks (mainly in spring and lower in autumn) in Italy with important geographical variations. This information may have clinical relevance in managing patients allergic to Parietaria.

Galactose-α-1,3-galactose syndrome: an Italian survey.

SUMMARY: Background. The term of α-Gal syndrome, which includes the delayed allergy to red meat and the allergic reactions following the administration of cetuximab, is associated to the presence of specific IgE to α-Gal. In Italy, only anecdotal cases were reported so far. The Association of Italian Allergists (AAITO) carried out a survey with the aim of evaluating presence, characteristics, clinical features, and distribution of the syndrome in Italy. Methods. A web structured questionnaire was made available on the website of AAIITO from July 2016 to January 2017. It included 31 multiple-choice questions concerning different items, including the site of physicians, the number of patients diagnosed as having cetuximab allergy and/or delayed red meat allergy, recall of tick bites, symptoms, time to reactions, elicitor foods, reactions with foods other than meat, and in-vivo and in-vitro tests used for the diagnosis. Results. Seventy-nine physicians completed the questionnaire. Nine cases of allergy to cetuximab and 40 cases of delayed red meat allergy were recorded across Italy. 22.5% of patients with cetuximab allergy and 62.5% of those with delayed red meat allergy recalled a tick bite. 75% of patients with delayed red meat allergy experienced symptoms after eating beef (butcher's cut in 72.5%). Urticaria was the most frequent clinical manifestation (65% of cases). In 60.6% of cases symptoms appeared 2 - 4 hours after meat ingestion, while in 7.9% symptoms appeared after > 4 hours. The most used diagnostic methods were the intradermal test for cetuximab allergy (88.9%) and the detection of IgE to α-Gal (55.5%) for red meat allergy. Most case reports came from Northern Italy. Conclusions. α-Gal syndrome is present in Italy and beef is the most frequent offending food. In most cases symptoms were not severe.

The importance of educating subjects entitled to use an adrenaline auto-injector for self-administration.

An educational program, consisting in a clear explanation of the technical aspects and use of the adrenaline auto-injection devices (AAD) and in a practical test utilizing a demonstration kit was given to 350 patients from our outpatient clinic. AAD was also distributed to 50 patients formerly followed by another allergy clinic without training. At practical control test, only 10% of the untrained patients where able to correctly use the AAD versus 80% of trained subjects. Since AAD is a life-saving procedure in severe anaphylactic episodes, this attempt to improve the ability of the patient to comply with the procedure can improve the efficacy of the treatment and eventually the patient's health.

Omalizumab treatment in patient with severe asthma and Eosinophilic Granulomatosis with Polyangiitis . A case report.

Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly named Churg Strauss Syndrome, is a multisystem disorder characterized by chronic rhinosinusitis, asthma, and prominent peripheral blood eosinophilia; it is classified as a vasculitis of the small and medium sized arteries, although the vasculitis is often not clinically apparent in the initial phases of the disease. We present the case of a woman with EGPA who was frequently treated with high dose steroid therapy during hospital admission for refractory asthma. After December 2008, the date when we started Omalizumab, we observed a significative reduction of circulating eosinophils and IgE serum level, and the patient was no more hospitalized for respiratory failure or asthma attacks.

Detection of 20 kDa and 32 kDa IgE-binding proteins as the major allergens in Italian sesame seed allergic patients.

BACKGROUND: Sesame seed allergy, a potentially very severe food allergy, seems on the rise worldwide but is still uncommon in Italy. The aim of the present study was to investigate the allergenic profile of Italian sesame seed-allergic patients. METHODS: Patients with genuine sesame seed allergy diagnosed over one year in a large number of allergy centers scattered through Italy were considered for the study. Their IgE reactivity to sesame seed allergens was characterized by immunoblot analysis. RESULTS: Eleven sesame seed allergic patients were detected and studied. 10/10 patients showed IgE reactivity against a sesame allergen at about 20 kDa, and 7/10 showed an extremely strong reactivity at about 32 kDa. The same 7 sera reacted also against a 28 kDa allergen, although such reactivity was significantly weaker in 6/7 cases. Eight patients showed IgE reactivity at about 48 kDa, and 5 sera reacted against higher m.w. proteins at about 67 kDa. Two sera showed IgE reactivity at about 43 kDa as well. Only one serum appeared to react to 2S-albumin. CONCLUSIONS: Italian sesame seed-allergic patients react mostly against allergens other than those described so far as major ones. A large number of recombinant sesame allergens will be needed for a comprehensive component- resolved diagnosis of allergy to this food.

Allergy to beer in LTP-sensitized patients: beers are not all the same.

BACKGROUND: Most cases of beer allergy reported so far have been associated with hypersensitivity to the non-specific lipid transfer protein (LTP). In view of the marked differences in brewing processes we assessed IgE reactivity as well as tolerance to many different beers in an allergic patient. METHODS: A 45 year-old man hypersensitive to grass pollen, cat dander and Alternaria tenuis with a history of urticaria and dyspnoea after drinking beer and a weak skin reactivity to commercial corn extract was studied. The patient underwent SPT with 36 different brands of beer and an open challenge with those scoring negative was performed. An immunoblot analysis was carried out using 2 SPT-positive beers, 2 SPT-negative beers, and barley, wheat, and maize extracts using both patient's serum and a maize LTP-specific in-house developed polyclonal antibody from rabbit. Further, the immune reactive LTP of one beer was separated by HPLC and the chromatogram was compared to that of purified maize LTP. RESULTS: Beer SPT scored positive in 30/36 cases. The immunoblot analysis showed IgE reactivity at about 10 kDa against the two SPT-positive beers and against maize with both patient's serum and the polyclonal anti-LTP rabbit serum, whereas the two SPT-negative beers, and barley extract scored negative. The immunodetected protein co-migrated with maize LTP. CONCLUSION: In beer-allergic patients the diagnostic workup may point to the detection of some tolerated products that can be consumed risk-free.

Shrimp allergy in Italian adults: a multicenter study showing a high prevalence of sensitivity to novel high molecular weight allergens.

BACKGROUND: Shrimp is a frequent cause of food allergy worldwide. Besides tropomyosin, several allergens have been described recently. OBJECTIVE: We investigated which allergens are involved in Italian shrimp-allergic adults. METHODS: Sera from 116 shrimp-allergic patients selected in 14 Italian allergy centers were studied. Skin prick tests with house dust mite (HDM) as well as measurements of IgE to Pen a 1 (shrimp tropomyosin) and whole shrimp extract were performed. All sera underwent shrimp immunoblot analysis, and inhibition experiments using HDM extract as inhibitor were carried out on some Pen a 1-negative sera. RESULTS: Immunoblots showed much variability. IgE reactivity at about 30 kDa (tropomyosin) was found in <50% of cases, and reactivity at about 67 kDa and >90 kDa was frequent. Further reactivities at 14-18, 25, 43-50, about 60 and about 80 kDa were detected. Most subjects had a history of shrimp-induced systemic symptoms irrespective of the relevant allergen protein. IgE to Pen a 1 were detected in sera from 46 (41%) patients. Skin reactivity to HDM was found in 43/61 (70%) Pen 1-negative subjects and inhibition studies showed that pre-adsorption of sera with HDM extract induced a marked weakening of the signal at >67 kDa. CONCLUSIONS: Several allergens other than tropomyosin are involved in shrimp allergy in adult Italian patients. Some hitherto not described high molecular weight allergens seem particularly relevant in this population and their cross-reactivity with HDM allergens makes them novel potential panallergens of invertebrates.

Prevalence of allergic disorders in Italy: the Cotignola population study.

BACKGROUND: The worldwide prevalence of allergic diseases such as rhinitis, asthma, and atopic dermatitis is continuously increasing, while other allergic disorders such as urticaria and angioedema are less investigated. We performed a population study evaluating the prevalence of any kind of allergic disorders. METHODS: The entire population of 7,201 inhabitants of Cotignola (Ravenna, Italy) was surveyed by a questionnaire assessing symptoms related to rhinitis, asthma, anaphylaxis, skin symptoms and insect sting allergy as well as the features of clinical presentations, diagnosis, and treatment received. RESULTS: Valid questionnaires were obtained by 6,676 inhabitants (92.7%). The sample was formed by 3,266 males and 3,495 females, the mean age was 45.6 years; 1,035 subjects (15.5%) were aged less than 18 years; 404 subjects (6%) had at least one episode of wheezing/breathlessness in their lifetime, and 243 of them (60.1%) had a diagnosis of asthma; 1,002 subjects (14.8%) had nose symptoms in their lifetime, and 375 of them (37.4%) had a diagnosis of allergic rhinitis or rhinoconjunctivitis. For other allergic manifestations, data were obtained from 5,730 subjects; of them, 178 (3.1%) had skin symptoms, 59 (1.1%) had oral symptoms, and 37 (0.6%) had anaphylaxis; 207 (3.6%) had reactions to insect stings. There were no significant differences in prevalence between Italians and immigrants. Only 51.7% of subjects with asthma, 46.5% of those with rhinitis, 22.7% of those with other allergies, but 97.1% of those with insect allergy, received treatment. CONCLUSIONS: These findings confirm recent data on epidemiology of allergic diseases in Europe, particularly in Italy, and add some details on how such diseases are managed.

Fever of unknown origin as unique symptom of an indolent mastocytosis.

A 39-years-old man afferred to our hospital for a fever lasting for more than 6 months, without abnormalities at physical examination (in particular no skin alterations); a recent laboratory and instrumental investigation was ineffective and so a fever of unknown origin (FUO) was diagnosed Since he reported an history of infantile mastocytosis (usually auto-resolving) we evaluated his serum-tryptase levels that resulted of 49 ug/L (normal value 20 ug/L), raising the doubt of the presence of an active mastocytosis. The following bone marrow evaluation showed aggregates of CD117 positive cells and a c-Kit point mutation at codon D 816V confirming the diagnosis of indolent mastocytosis.The present case confirm that FUO can be caused by an otherwise asymptomatic indolent mastocytosis, thus suggesting to include the serum-tryptase level measurement in the diagnostic approach to this pathological condition, at least in selected cases.

Are IgE levels to foods other than rosaceae predictive of allergy in lipid transfer protein-hypersensitive patients?

BACKGROUND: Lipid transfer protein (LTP), the most frequent cause of primary food allergy in Italy, is a cross-reacting plant pan-allergen. Markers able to predict whether a patient sensitized to a certain food but not yet clinically allergic will develop allergy would be extremely helpful. OBJECTIVE: It was the aim of this study to investigate the relevance of IgE levels to some plant foods other than Rosaceae as predictors of either local or systemic allergic reaction in LTP-allergic subjects. METHODS: One hundred (40 males, 60 females , mean age 29 years) peach-allergic patients monosensitized to LTP seen at 14 Italian centres in 2009 were studied. Walnut, hazelnut, peanut, tomato, rice and/or maize allergy was ascertained by interview and confirmed by positive skin prick test. IgE levels to these foods and to rPru p 3 were measured. RESULTS: Higher levels of IgE to Pru p 3 were associated with a higher prevalence of allergy to hazelnut, peanut and walnut. For all study foods, except rice, median IgE levels in allergic subjects significantly exceeded those in tolerant subjects, though within single allergic groups, the differences between patients reporting systemic or local (oral) symptoms were not significant. Ninety-five percent cut-off IgE levels predictive of clinical allergy were established for study foods although the marked overlaps between allergic and tolerant subjects made them of limited usefulness. CONCLUSION: Specific IgE levels are only partially predictive of clinical allergy. The reasons why some individuals showing low specific IgE levels develop clinical allergy whereas others showing high IgE levels do not, despite similar exposure to the allergen, remain unclear.

Efficacy and safety of sublingual immunotherapy with grass monomeric allergoid: comparison between two different treatment regimens.

BACKGROUND: Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid proved to be well tolerated, safe and effective in patients with respiratory allergy. Standard administration regimens are expected to require a long time before clinical benefit can be appreciated. We investigated whether pre-seasonal and perennial regimens differently affect the clinical efficacy of grass pollen SLIT. METHODS: Adult patients with allergic rhino-conjunctivitis with/without mild intermittent asthma due to grass pollen were included into this open prospective study and randomised to receive SLIT with a continuous regimen (Group 1: 1,000 AU/week for the entire study period) or a pre-seasonal regimen (Group 2: 5,000 AU/week for 10 weeks/year for 2 years), or on demand drug therapy alone (Group 3) for two years. At entry (November 2005), at the end of the first and second pollen season, a Visual Analogue Scale (VAS) was used to assess patients' well-being. Symptom score and drug consumption were evaluated during the seasons. Methacholine challenge was performed at study entry and conclusion. Adverse events were recorded along the whole study duration. RESULTS: Thirty-two patients were divided into Group 1 (n = 10), Group 2 (n = 11) and Group 3 (n = 11). A significant VAS improvement was observed in both SLIT groups, after the first and second pollen season, compared to baseline and to Group 3 (p < 0.05). Less symptoms and need for medications resulted during the second season (p < 0.05). No relevant variations in bronchial hyper-reactivity have been observed between the three groups. Only 2 patients experienced local or mild reactions in SLIT groups. CONCLUSION: Both pre-seasonal and continuous regimen of SLIT with monomeric allergoid turned out effective and safe, suggesting that a pre-seasonal course with 5,000 AU/week for 10 weeks may represent a convenient option in patients with grass pollen allergic rhinitis with/without mild intermittent asthma. Further research is urgently needed to consolidate these preliminary evidences.

Patients monosensitised to Hev b 8 (Hevea brasiliensis latex profilin) may safely undergo major surgery in a normal (non-latex safe) environment.

BACKGROUND: Natural rubber latex allergy is a condition at high risk of anaphylaxis during surgery. However, latex contains several protein allergens and not all of them may show the same clinical relevance. OBJECTIVE: To investigate the clinical relevance of Hey b 8, the natural rubber latex profilin. METHODS: Seven patients without a clinical history of latex allergy but identified as being latex hypersensitive by positive SPT (3/7) and or positive latex-specific IgE during routine pre-surgery allergy investigations were studied. All patients were monosensitized to Hev b 8 (Hevea brasiliensis latex profilin) as shown by the detection of specific IgE to recombinant latex allergen components. Ten subjects with a history of latex allergy (urticaria, asthma, and/or rhinitis), sensitised to latex allergens other than profilin were enrolled as controls. Both patients and controls underwent a latex glove-wearing test; in case of a negative test, patients underwent surgery in a normal surgical setting. RESULTS: All 7 patients scored negative on latex glove wearing test and underwent major surgery (orthopaedic, Caesarean section, pilonidal sinus, vascular, tonsillectomy, uterine revision, and uretral surgery) in a normal (non-latex safe) surgical setting without any consequence. In contrast, 9/10 (90%) controls showed a positive latex glove-wearing test (p < 0.01). CONCLUSION: Latex profilin is either clinically irrelevant or is no longer present in latex products. This study highlights the importance of a component-resolved diagnosis of latex sensitisation as a tool to get a more precise assessment of the risk and to reduce the costs of healthcare.