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.

Delayed corticosteroid hypersensitivity: a clinical management proposal.

Summary: Background. Different clinical pictures are related to corticosteroids (CS) non immediate hypersensitivity and the frequency of these reactions can be underestimated. The classification of CS in 3 groups and the identification of two patient's profiles has been proposed by Baeck to help clinicians in the management of these cases. Methods. Data of 14 patients with clinical history of delayed reactions to various CS and positive skin test and/or oral challenge are retrospectively analyzed. Results. Three different patterns of patients are identified evaluating history, clinical picture and tests results. The first one (6 pts, 43%) is characterized by cutaneous and/or mucosal reaction due to inhaled Budesonide and patch test positive only to topical molecules belonging to the group 1 of CS. The second pattern (4 pts) has clinical history of local and systemic skin reactions to the topic and parenteral administration of the same or other steroid drugs. Patients belonging to the third pattern (4 pts) have a history of systemic reactions to general administration of CS without previous contact reaction. Pattern 2 and 3 show a wide sensitization to molecules belonging to the 3 groups of CS. All the patients show patch test positive to Budesonide. Conclusions. Although the lack of standardization, the allergy workup proves useful to differentiate patients sensitized to one or few molecules from polysensitized and to identify the culprit drugs. Intradermal and challenge test are necessary to complete the diagnostic workup. The results suggest the possibility of a different management of patients. Patients of pattern one can be only patch tested with a limited series of CS belonging to the 3 groups. They don't need an extensive exclusion of steroids use. The pattern 2 and 3 must be submitted instead to a complete allergological individual evaluation to identify alternative tolerated drugs, because of the risk of systemic reactions. The Baeck's classification shows limited usefulness in these cases.

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Assessing clinical and psychological features: who are patients showing a nocebo re-action during the drug challenge test?

Summary: The nocebo reaction, namely the undesirable effect of an inert substance (placebo), is a phenomenon rarely investigated in literature. A better knowledge of this reaction may help clinicians in the management of these patients in clinical practice. Patients with drug adverse reactions (ADR) undergoing the drug challenge test are an ideal model for studying the nocebo effect, and the study aims to investigate their clinical and psychological features. One hundred and twenty patients (Mage = 46.59, SD = 15.5; 82% female), of which 90 non responders and 30 with nocebo reactions (25%) were recruited, and completed a battery of psychological measures: State-Trait Anxiety Inventory X1-X2, Beck Depression Inventory II, Symptoms Checklist-90-R, Difficulties in Emotion Regulation Scale, Toronto Alexithymia Scale. Clinical features (individual characteristics and ADR clinical history) were collected by clinicians. The results show that older age (p = 0.002), low level of education (p = 0.039) and a depressive tendency (p = 0.030) appear to be potential risk factors for nocebo effects. Although none of the features related to the previous clinical history appear to represent a risk factor for the nocebo reactions (p minor 0.05), significant correlations between some of the clinical and psychological characteristics considered (p values from 0.005 to 0.042) help to better delineate the profile of these reactive patients. A specific training of the sanitary team about psychological aspects is recommendable.

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.

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.

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.

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).

Proposal of a skin tests based approach for the prevention of recurrent hypersensitivity reactions to iodinated contrast media.

The purpose of the present work is to evaluate the efficacy of an approach that combines clinical history, skin tests results, and premedication, in preventing recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin Prick tests, Intradermal tests, and Patch tests were performed in 36 patients with a previous reaction to ICM. All patients underwent a second contrast enhanced radiological procedure with an alternative ICM selected on the basis of the proposed approach. After alternative ICM re-injection, only one patient presented a mild NIR. The proposed algorithm, validated in clinical settings where repeated radiological exams are needed, offers a safe and practical approach for protecting patients from recurrent hypersensitivity reactions to ICM.

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.

Successful desensitization to natalizumab in a skin test--positive patient: a case report.

Relevant interest has been focused on rapid desensitization for drug hypersensitivity and on its use for reactions to monoclonal antibodies. Natalizumab is a highly effective therapy for multiple sclerosis but its use can be limited by hypersensitivity reactions. Herein we present a case of a 36-year-old male patient with multiple sclerosis who started natalizumab therapy due to rapid neurological deterioration. During the second infusion he developed a reaction involving urticaria, erythema and angioedema. Natalizumab sensitization was demonstrated by a positive result on the intradermal test. The anti-natalizumab IgG neutralizing antibody assay was negative. Lacking any alternative, equally effective treatment, he underwent a rapid intravenous desensitization protocol. Desensitization was successfully repeated eleven times and the patient's neurological conditions improved and remained stable after one year. This case demonstrates that rapid desensitization is a safe and effective procedure in the treatment of natalizumab hypersensitivity.

Bet v 1-like pollen allergens of multiple Fagales species can sensitize atopic individuals.

BACKGROUND: In the temperate climate zone of the Northern hemisphere, Fagales pollen allergy represents the main cause of winter/spring pollinosis. Among Fagales trees, pollen allergies are strongly associated within the Betulaceae and the Fagaceae families. It is widely accepted that Fagales pollen allergies are initiated by sensitization against Bet v 1, the birch pollen major allergen, although evidence is accumulating that the allergenic activity of some Bet v 1-like molecules has been underestimated. OBJECTIVE: To investigate the allergenic potential of the clinically most important Fagales pollen allergens from birch, alder, hazel, hornbeam, hop-hornbeam, oak, beech and chestnut. METHODS: To obtain the full spectrum of allergens, the three previously unavailable members of the Bet v 1-family, hop-hornbeam Ost c 1, chestnut Cas s 1 and beech Fag s 1, were identified in the respective pollen extracts, cloned and produced as recombinant proteins in E. coli. Together with recombinant Bet v 1, Aln g 1, Car b 1, Cor a 1 and Que a 1, the molecules were characterized physicochemically, mediator release assays were performed and IgE cross-reactivity was evaluated by ELISA and Immuno Solid-phase Allergen Chip (ISAC) IgE inhibition assays. RESULTS: All allergens showed the typical Bet v 1-like secondary structure elements, and they were all able to bind serum IgE from Fagales allergic donors. Strong IgE binding was observed for Betuloideae and Coryloideae allergens, however, cross-reactivity between the two subfamilies was limited as explored by inhibition experiments. In contrast, IgE binding to members of the Fagaceae could be strongly inhibited by serum pre-incubation with allergens of the Betuloideae subfamily. CONCLUSIONS AND CLINICAL RELEVANCE: The data suggest that Bet v 1-like allergens of the Betuloideae and Coryloideae subfamily might have the potential to induce IgE antibodies with different specificities, while allergic reactions towards Fagaceae allergens are the result of IgE cross-reactivity.

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.

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.

Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double-blind study.

A double-blind, placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route. The patients were assessed before and after a 10-month period of treatment by clinical (symptom-medication scores and specific nasal reactivity) and immunological (total IgE, specific IgE, IgG and IgG4 antibodies) parameters. High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects. The actively treated patients had significantly lower medication scores than those on placebo (p < 0.05) when the maximum pollen count was recorded, and at the end of the trial they showed a significant decrease in nasal reactivity (p < 0.02) and a significant increase in serum specific IgG4 (p = 0.02). No differences were detected in any of these parameters in the placebo group. Possible explanations for the mechanisms of sublingual immunotherapy are proposed.