Hypersensitivity reactions to iodinate contrast media in Italy: a retrospective study. Characteristics of patients and risk factors.

SUMMARY: Objective. The purpose of the study was to describe the characteristics of patients experiencing hypersensitivity reactions (HRs) to iodinated contrast media (ICM) in a large Italian population and to investigate potential risks factors in order to obtain a risk stratification, helpful in the management of these patients. Methods. Data of 407 patients investigated in 9 Italian Allergy Centers for suspected HRs to ICM were analyzed and compared with a control group of 152 subjects that tolerated one or more ICM-enhanced examinations. The univariate and multivariate logistic regression model was used to evaluate associated factors. Results. The mean age of reactive patients was 61 years and 60% were female; 67% of patients reported immediate reactions and 35% experienced the reaction, more frequently with immediate onset, at the first examination in life. Iomeprol, iopromide and iodixanol were the most frequent culprit agents and 20% of patients showed a positive skin test result. Previous adverse reactions to ICM were reported by 15.6% of patients, whereas 35% of subjects experienced the reaction, more frequently immediate, after the first ICM-enhanced examination in their life. The multivariate analysis showed that male gender and age > 65 were associated with ICM reactions as protective factors [ORadja = 0.51; 95% CI: 0.33-0.77 and ORadja = 0.60; 95% CI: 0.39-0.92 respectively]. Cardio-vascular disease [ORadja = 2.06; 95% CI: 1.22-3.50)], respiratory allergy [ORadja = 2.30; 95% CI: 1.09-4.83)] and adverse drug reactions [ORadja = 1.99; 95% CI: 1.05-3.77)] were identified as risk factors for ICM reactions. Food allergy was not significantly associated with reactions [ORadja = 1.51; 5% CI: 0.41-5.56]. Conclusions. This is the largest study on Italian patients experiencing hypersensitivity reactions to ICM. Most results are in line with other studies, showing some association with factors that could influence the incidence of hypersensitivity reactions but not allowing an easy risk stratification.

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.

Evaluation of two commercial peach extracts for skin prick testing in the diagnosis of hypersensitivity to lipid transfer protein. A multicenter study.

Summary: The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p1, Pru p3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein (LTP) and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit.

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.

Recommendations for the use of molecular diagnostics in the diagnosis of allergic diseases.

Summary: The Study Group on Allergology of the Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL) and the Associazione Italiana degli Allergologi e Immunologi Territoriali e Ospedalieri (AAIITO) developed the present recommendations on the diagnosis of allergic diseases based on the use of molecular allergenic components, whose purpose is to provide the pathologists and the clinicians with information and algorithms enabling a proper use of this second-level diagnostics. Molecular diagnostics allows definition of the exact sensitization profile of the allergic patient. The methodology followed to develop these recommendations included an initial phase of discussion between all the components to integrate the knowledge derived from scientific evidence, a revision of the recommendations made by Italian and foreign experts, and the subsequent production of this document to be disseminated to all those who deal with allergy diagnostics.

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.

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.

Demonstration of an IgE-mediated immunological pathogenesis of a severe adverse reaction to gadopentetate dimeglumine.

In this case report, the authors, after reviewing the literature data about contrast agents in Magnetic Resonance Imaging (MRI) and correlated problems, investigate the immunological mechanism of an adverse reaction to gadopentetate dimeglumine (Gd-DTPA), in order to demonstrate an IgE-mediated immunological pathogenesis. The case of a patient who underwent MR imaging in our hospital was studied. During, and after, the MR examination with Gd-DTPA the patient showed local warmth/pain to the external genitalia and to the face, tachycardia, nausea, vomiting, diarrhea, uterine cramps, and diffuse cutaneous rash. Skin tests (intradermal) and the passive transfer test according to Prausnitz and Küstner were positive, suggesting the involvement of an I-type allergy (IgE-mediated) mechanism. In this paper, we demonstrate that the adverse reactions to Gd-DTPA can be supported by an immunological mechanism.

[Mucocutaneous lichen planus with esophageal involvement. A clinical case]. / Lichen planus muco-cutaneo con coinvolgimento esofageo. Un caso clinico.

The paper reports the case of a 58-year-old woman suffering from mucosal and cutaneous lichen planus (LP) with esophageal and oral involvement, who had complained of dysphagia for approximately the past two years. The diagnosis of esophageal LP was made using esophagoscopy with mucosal biopsy. The differential diagnosis between LP and progressive systemic sclerosis is discussed; a cold-test, plethysmography of the limbs, an anti-ENA Sci-70 antibody assay, X-rays of soft tissues and esophagomanometry were performed for this purpose, and all proved normal. The presence of conditions implicated in the etiopathogenesis of LP (psychic disorders and the administration of psychoactive drugs, anti-hypertensives and FANS) were observed, together with an already known association with arterial hypertension. Altered hepatic function (with an increase in cholestasis enzymes) was also noted which is probably attributable to the prolonged use of psychoactive drugs (hepatic biopsy showed severe steatosis).

Anaphylactic shock after skin test with phytohaemoagglutinin.

A young woman (26 years old), with gastrointestinal candidosis of 8 months duration, was hospitalized in our department to study her cell immunity. Five minutes after an id injection of PHA (bactophytohaemoagglutinin M, Difco, 1 mg), mix monilieae, mix tricophyton and PPD Berna, she showed an extensive wheal and flare reaction in the PHA injection area, eyelid oedema and respiratory distress. In spite of adrenaline, corticosteroid and antihistamine drug administration, the patient collapsed and was admitted to the resuscitation department, where she quickly recovered. In the following days, the patient underwent immune and allergy testing: 1) total Ige immuno-enzymatic assay: 72 KU/1; 2) specific IgE and IgE immuno-enzymatic assay for Candida: negative; 3) in vitro lymphocyte transformation test (thymidine 2-C14) with PHA Difco was positive. This finding and the positivity of the id injection with PHA could indicate an allergic type I immunoreaction, the description of which we have not found in the international literature (the presence of IgG STS cannot be totally excluded).

Episodic angioedema with eosinophilia (Gleich syndrome).

A case of episodic angioedema with hypereosinophilia or otherwise called Gleich's syndrome is reported. The patient was a young woman with a six-year history of recurrent angioedema, itchy urticaria, rapid weight gain and hypereosinophilia. The main clinical, laboratory, and immunological findings included systemic angioedema, urticaria, 12% weight gain and leucocytosis (69.150 WBC/cu mm) with eosinophils of 75.6%. Circulating IgM, IgE, and T-helper lymphocyte were elevated. Skin biopsy showed an important perivascular eosinophil infiltration. The absence of concomitant allergic, malignant and connective disorders, and a dramatic clinical improvement with a fall of the eosinophil count to normal levels following corticosteroid therapy was the basis for our diagnosis.