Shrimp Allergy: Analysis of Commercially Available Extracts for In Vivo Diagnosis.

BACKGROUND AND OBJECTIVE: Skin prick testing (SPT) with commercial extracts is the first step in the diagnosis of shrimp allergy, although its clinical efficiency is unknown. Objective: To analyze the clinical usefulness of all commercial crustacean extracts available for SPT in Italy. METHODS: We performed a multicenter study of 157 shrimp-allergic patients who underwent SPT with 5 commercial crustacean extracts and with house dust mite (HDM) extract. Commercial extracts were analyzed using SDS-PAGE and compared with a freshly prepared in-house shrimp extract. IgE to Pen a 1/Pen m 1, Pen m 2, and Pen m 4 was determined, and immunoblot analysis was performed on a large number of sera. RESULTS: The skin reactions caused by commercial crustacean extracts were extremely heterogeneous, resulting in 32 clinical profiles, with marked differences in protein content and missing proteins at molecular weights corresponding to those of major shrimp allergens. Only strong Pen a 1/Pen m 1 reactors reacted to both HDM and all 5 commercial extracts in SPT. Most patients, including those who were tropomyosin-negative, reacted to HDM. Patients reacted to a large and variable array of proteins, and IgE reactivity was common at high molecular weights (>50 kDa). CONCLUSIONS: The in vivo diagnosis of shrimp allergy must continue to be based on SPT with fresh material. Shrimp-allergic patients frequently react to a number of ill-defined high-molecular-weight allergens, thus leaving currently available materials for component-resolved diagnosis largely insufficient. Mites and crustaceans probably share several allergens other than tropomyosin.

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.

A regional approach to unmet needs in anaphylaxis.

Allergic diseases are under-diagnosed and undertreated despite their wide prevalence, and particularly anaphylaxis is often under-estimated. Evidence-based anaphylaxis guidelines developed by principal allergy organizations agree on increased prevalence of anaphylaxis, especially in patients younger than 18 years (18-27,30): this trend highlights the need for actions on anaphylaxis management and prevention (3,4). Lack of prompt connection between emergency department and allergy unit after discharge, and of a dedicated ICD-9th identification code (18-26), can delay diagnosis and treatment of anaphylaxis (28,29). Also in the experience of our Allergy Unit, patients reach the allergist office after several attacks treated in ED (17), without a previous evaluation and risk assessment. Keeping in mind unmet needs in anaphylaxis (4), we focused on regional approaches to health care delivery. The key point of our project was to establish an active collaboration between allergist clinicians and their counterparts in emergency medicine, with a system of quick filing report of patients discharged from ED with the suspect of anaphylactic reaction, directed to a central allergy unit, acting in a hub and spoke model with the Ligurian allergy network (31). Aim of the project was to improve epidemiological data collection via direct connection among ED and allergy network; moreover, we tried to provide a quick and proper evaluation of all reported patients, identifying, when possible, the agent responsible for anaphylaxis, to provide instructions on how to minimize future exposure; as all individuals at risk for anaphylaxis should carry and know how to self-administer epinephrine, we managed to provide auto injector and proper training when appropriate. A follow up on readmissions was carried out during the study and four months later. In a 20 months observation period (2013/2014), 205 patients were reported: it was possible to reach a diagnosis and risk assessment in 64.3%. Anaphylaxis diagnosis was considered likely if any 1 of 3 criteria is satisfied within minutes to hours: acute onset of illness with involvement of skin, mucosal surface, or both, and at least 1 of the following: respiratory compromise, hypotension, or end-organ dysfunction; 2 or more of the following occur rapidly after exposure to a likely allergen: involvement of skin or mucosal surface, respiratory compromise, hypotension, or persistent gastrointestinal symptoms; hypotension develops after exposure to a known allergen for that patient: age-specific low blood pressure or decreased systolic blood pressure more than 30% compared with baseline. Of 205 patients reported, 132 were classified as severe anaphylaxis; other 73 cases reported were 12 drugs related angioedema (mostly NSAID related), 9 ACEi related angioedema, 3 ereditary C1inh deficiency angioedema, 24 istaminergic idiopatic angioedema, 14 urticaria angioedema, 6 severe asthma, 2 latex reactions; in three patients a proper diagnosis was not achieved due to refuse / impossibility to perform diagnostic workout. Hymenoptera venom and food proved to be the main triggers, followed by drugs. 100% patients at risk of anaphylaxis received self-injectable adrenaline, pertinent education and individual action plan. In the same period, even though short, there were only two readmissions to ED. First result seems to confirm the usefulness of our approach to address some of unmet needs in anaphylaxis management, as recently pointed out by ICON guidelines (4).

New risks from ancient food dyes: cochineal red allergy.

This study reports an unusual case of IgE-mediated hypersensitivity to Cochineal red or Carmine red, a coloring agent of natural origin. Although the risk of anaphylactic reactions is well known, since the nineties the use of this additive seems to be nowadays on the rise. The problem of labeling of additives used in handmade food products is highlighted.

Bovine Serum Albumin: a double allergy risk.

We analyse two cases of Bovine Serum Albumin (BSA) allergy. The first regards a female laboratory technician with a history of bronchial asthma due to cat allergy, who developed an exacerbation of bronchial symptoms as a consequence of BSA powder inhalation at work. To date, sensitization to BSA as a cause of occupational asthma has rarely been reported in the scientific literature. The second case concerns a woman with a similar cat sensitivity, who presented an oral allergy syndrome-type clinical reaction, gastric pain and diarrhoea immediately after eating cooked pork meat. Subsequently, she developed the same reaction after eating goat meat and goat cheese, and then also after eating beef. Both patients resulted specifically sensitized to BSA and to other mammalian serum albumins which play a role as panallergens in animals. The two cases show that BSA, a well known cause of food allergy in childhood, may also provoke symptoms of food allergy in adulthood, though in case of powder inhalation, it may provoke respiratory symptoms. Prior animal sensitization appears to represent a risk factor.

Heterogenity of IgE response to walnut and hazelnut in Italian allergic patients.

BACKGROUND: The prevalence of IgE reactivity against genuine walnut and hazelnut allergens is poorly defined. OBJECTIVE: The IgE response to walnut and hazelnut was investigated in Italian patients with primary allergy to these nuts. METHODS: Sera from 36 patients allergic to hazelnut and/or walnut, not reactive to PR-10, profilin, and LTP, underwent immunoblot analysis with extracts of both nuts. RESULTS: Most patients had a history of systemic symptoms following the ingestion of the offending food(s). Twelve patients were sensitized to both walnut and hazelnut, and 13 were sensitized to other nuts and seeds (cashew, peanut, sesame, pine nut, almond, Brazil nut, and pistachio). On walnut immunoblot, the 7 sera which scored positive showed much variability in their IgE profile. Two reacted uniquely at 10 kDa, and the others at 35 , 40, 45, 50, 67, and > 67 kDa. The profiles obtained under reducing and non-reducing conditions showed several differences. The 7 sera positive on hazelnut immunoblot under reducing conditions recognized sera at 10 kDa and at <10 kDa (n=1), 20 kDa (n=4), at about 22, 24, 30, 40, 43, 58, 60, and 90 kDa, and higher m.w. in other cases. Under non-reducing conditions IgE reactivity at 20, 28, 35, 40, 45, 60, 90, and 100 kDa, was detected. Only two sera scored positive under both conditions and showed an IgE profile that partly changed from one assay to another. CONCLUSION: The current list of walnut and hazelnut allergens is far from being complete. Both reducing and non-reducing conditions are needed to detect IgE reactivity in individual patients.

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.

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.

Epinephrine autoinjector prescription in food-allergic adults: symptom-based only or allergen-based also? An Italian multi-centre study.

BACKGROUND: Epinephrine is the treatment of choice for acute food-allergic reactions but existing guidelines state that it should be prescribed uniquely to patients who already experienced at least one food-induced anaphylactic episode. OBJECTIVE: We investigated whether in Italy epinephrine auto-injector is prescribed uniquely following the existing guidelines only, or is allergen-informed as well (i.e., based on the potential risk associated with sensitization to certain food allergens), and hence preventive. METHODS: 1110 adult patients (mean age 31 years; M/F 391/719) with food allergy seen at 19 allergy outpatient clinics were studied. Patients with a history of probable anaphylaxis were identified. Subjects were classified as having primary (type 1) and/or secondary (type 2) food allergy and were divided into several subgroups based on the offending allergen/food. Epinephrine prescriptions were recorded and analyzed both as a whole and by sensitizing allergen. RESULTS: Epinephrine was prescribed to 138/1100 (13%) patients with a significant difference between subjects with type-1 and type-2 food allergy (132/522 [25%] vs. 6/629 [1%]; p < 0.001). The epinephrine group included most patients with a history of anaphylaxis (55/62 [89%]) or emergency department visits 106/138 (77%). In some specific subsets, namely fish-, tree nuts-, and lipid trasfer protein (LTP)-allergic patients, epinephrine was prescribed to patients without a history of systemic allergic reactions. CONCLUSIONS: Italian allergy specialists prescribe epinephrine auto-injectors both on the basis of clinical history of severe reactions and on a critical analysis of the hazard associated with the relevant protein allergens, which suggests a good knowledge of allergens as well as acquaintance with the guidelines for prescription of emergency medication.

EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study.

BACKGROUND: Studies of the prevalence of different types of food allergy in adults are lacking. OBJECTIVE: To define the prevalence of IgE-mediated food allergies in Italian adults attending allergy clinics and to assess possible differences associated with geographical position and/or dietary habits. METHODS: Seventeen allergy outpatient clinics scattered throughout Italy participated to a multi-centre study in 2007. The number of atopic subjects and of food allergic patients along with clinical features were recorded by pre-defined criteria. Patients with unequivocal history of food allergy confirmed by positive skin prick test were included as cases. RESULTS: Twenty five thousand six hundred and one subjects were screened; 12,739 (50%) were atopic, and 1079 (8,5%) had IgE-mediated food allergy. Sixty four percent of patients were females. Overall, the most frequent food allergy was the pollen-food allergy syndrome (55%), which was associated with oral allergy syndrome in 95% of cases and whose frequency decreased southbound. Forty-five percent of patients had a type 1 food allergy, in most cases (72%) caused by fruits and vegetables, and generally associated with a history of systemic symptoms. Type 1 food allergies represented 96% of food allergies in the South. Lipid transfer protein (LTP) accounted for 60% of sensitizations and caused most primary food allergies in all areas. CONCLUSION: Plant-derived foods cause most food allergies in Italian adults. The pollen-food allergy syndrome is the most frequent type of food allergy followed by allergy to LTP whose frequency increases southbound. The pattern of allergy to certain foods is clearly influenced by specific geographic features such as pollen exposure and dietary habits.

Causes of food-induced anaphylaxis in Italian adults: a multi-centre study.

BACKGROUND: Data about food-induced anaphylaxis in Italy are missing. OBJECTIVE: It was the aim of this study to detect the main foods/food allergens causing anaphylaxis in Italy. METHODS: The frequency of anaphylaxis and the relative importance of many offending foods were assessed in 1,110 adult patients with food allergy diagnosed by common criteria at 19 allergy centres scattered throughout Italy from 1 January to 31 December 2007. RESULTS: Fifty-eight of 1,110 (5%) food-allergic patients experienced at least 1 episode of anaphylaxis. On average, they were older than other food-allergic patients (34 vs. 31 years; p < 0.05). The majority of anaphylactic episodes occurred in patients sensitized to lipid transfer protein (LTP; n = 19), followed by shrimp (n = 10), tree nuts (n = 9), legumes other than peanut (n = 4), and seeds (n = 2); peanut, spinach, celery, buckwheat, wheat, avocado, tomato, fish, meat, and Anisakis caused an anaphylactic reaction in single patients. Among LTP-hypersensitive patients, peach caused 13/19 anaphylactic episodes. Shrimp-allergic patients were significantly older than other patients with food-induced anaphylaxis (p < 0.05), whereas patients allergic to LTP experienced their anaphylactic episodes at a younger age (p < 0.001). The frequency of anaphylaxis among patients sensitized to LTP, shrimp or tree nuts did not differ between northern and central/southern Italy. CONCLUSION: LTP is the most important allergen causing food-induced anaphylaxis in Italy, peach being the most frequently offending food. Peanut-induced anaphylaxis seems very uncommon. Geographic and environmental differences both between Italy and other countries and within Italy seem to play a relevant role in the pattern of sensitization to foods.

Phenobarbital-induced DiHS and ceftriaxone hypersensitivity reaction: a case of multiple drug allergy.

Patients with DiHS show an increased risk of sensitization to multiple drugs. We report a case of a young woman who developed cutaneous rash, lymphoadenopathy, malaise and fever after the introduction of phenobarbitale. Because of these symptoms, she was treated with ceftriaxone and she experienced a severe flare-up of the cutaneous and general reaction. Allergological work-up, by cutaneous and lymphocyte transformation test, confirmed a double sensitization to phenobarbital and ceftriaxone. In conclusion, the high risk of DiHS during anticonvulsive therapy should suggest caution in using additional drugs, because of an increased risk of multiple reactions.

Phytohemagglutinin or pokeweed mitogen induction of in vitro colony formation by T-cells from patients with chronic lymphocytic leukemia.

The colony-forming capacity of peripheral blood T-cells isolated from B-cell chronic lymphocytic leukemia patients was studied and compared with that of peripheral blood T-cells isolated from 2 groups of normal controls (young and aged healthy donors). Upon stimulation with phytohemagglutinin or pokeweed mitogen. T-cells from both the patients and the controls developed into colonies but only in the presence of the appropriate conditioned media. When the responses of the 3 groups were compared, no statistically significant differences were detected. However, the number of patients who failed to respond to phytohemagglutinin was larger than that of normal controls. Studies on a selected group of patients demonstrated that such unresponsiveness was unrelated to the presence of suppressor cells or to inadequate conditions used for stimulation in culture. Rather, this unresponsiveness may be connected with an intrinsic T-cell defect present in certain B-cell chronic lymphocytic leukemia patients.

Chronic urticaria: importance of a medical-psychological approach.

Chronic urticaria is often associated with psychological factors, such as depression, anxiety and stress, which may play a role not only in the genesis of the disease but also in its evolution. Aims of this study were to evaluate the utility of psychological assessments (presence of depression, impact on the quality of life and incidence of "life events" before the beginning of urticaria) in conjunction with the allergological evaluation and to provide appropriate treatment to the patients selected. Thirty subjects diagnosed as Chronic Urticaria patients were submitted to psychological assessments (semi structured interview, Beck Depression Inventory, Nottingham health Profile and Dermatology Life Quality Index). The results of the evaluation show that most of the patients experienced a "stressor" event within the six months before the onset of the cutaneous manifestation. The incidence of depression resulted very high in comparison with the general population and in three cases at a severe level. The impact on the quality of life results to be moderate, but involving different fields of life (physical image, social life, quality of sleeping and eating, etc). Despite these results, only six patients accepted to be assigned to an appropriate treatment. In conclusion, we demonstrate the usefulness of a medical- psychological approach in chronic urticaria and we confirmed the resistance of psychosomatic patients to undergo psychological treatment.

Psychological aspects of drug intolerance.

A consecutive unselected series of 50 patients suffering from drug intolerance was evaluated by allergological and psychological tests. We wanted to verify the existence of a correlation between some psychological characteristics (hysteria, depression and Ego Integrity), and some clinical aspects (number and type of episodes, severity and probability of the reactions). We confirmed the prevalence of female sex in these disorders, particularly in middle-aged married women. The mean score of hysteria in the whole sample was lightly higher than normal. Moreover a relevant number of subjects (24%) scored higher than the cut off for clinical depression, with a significant difference in comparison to the overall prevalence of depression in the general population. Finally, the analysis of clinical variables considered in our patients showed that subjects with a history of less serious reactions and unlikely reactions scored higher in depression and hysteria scales. The importance of psychological evaluation of drug intolerance patients is discussed and confirmed.

Management of patients at risk for adverse reactions to local anesthetics: analysis of 386 cases.

Local anesthetics are among the most used drugs in clinical practice. Various types of reactions have been reported and many patients are told that they are allergic to caines or are at risk of allergic reactions. We report our experience with 386 patients using skin test and progressive subcutaneous challenge in order to select a local anesthetic that could be safely used. The patients underwent specific protocol including clinical history, prick and intradermal tests, and subcutaneous incremental challenge with a local anesthetic from the amide group which was free of preservatives and vasoconstrictors. Thirteen patients showed a positive skin test: 10 with positive prick test underwent the subsequent challenge with no reactions; the three who were also positive by the intradermal route were carefully evaluated with a different drug. Eight of the patients with negative skin tests complained of various clinical symptoms after the challenge. All the patients found the local anesthetic to be well tolerated and nobody reported reactions after the clinical use. These results show that skin tests and subcutaneous challenge are safe and sufficient to reliably identify a local anesthetic that patients with a prior history of adverse reaction or at higher risk could tolerate.

Asthma and rhinitis in schoolchildren: the impact of allergic sensitization to aeroallergens.

This study aimed to evaluate the prevalence of asthma and rhinitis in schoolchildren living in the Genoa area by using a validated questionnaire and to investigate the prevalence of sensitizations using skin prick tests. An ATS modified questionnaire was given to 781 schoolchildren (all of them aged between 11 and 14 years) resident in the Genoa area. The main outcome of the present survey demonstrates a high prevalence of sensitized children (40.7%). Asthma and rhinitis prevalences are very high, mainly concerning the lifetime diagnosis. Actual asthma prevalence is about 6%, confirming ISAAC results, but rhinitis prevalence is notably higher and there is no difference between seasonal and perennial forms. Mites are the most important cause of sensitization and pollens are more frequently the cause of polysensitization. A distinct percentage of the asthmatic children and a higher percentage of rhinitic children are nonallergic. On the other hand, about one third of the sensitized children are without symptoms: They may be considered as subjects at risk of developing clinical respiratory diseases later. In conclusion, this study shows the importance of evaluating the existence of atopy, since there are many subjects with asthma and rhinitis who are nonallergic, and subjects at risk of developing respiratory allergies may be detected.

Hypersensitivity to imatinib: successful desensitization in a skin test-positive patient

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