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Eleonora Nucera,1 Sara Urbani,1 Alessandro Buonomo,1 Tiziana De Pasquale,2 Angela Rizzi,1 Arianna Aruanno,1 Stefano Pucci2 1Allergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 2Civitanova Marche Hospital, Civitanova Marche, ItalyCorrespondence: Eleonora NuceraAllergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito, 1, Rome, 00168, ItalyTel +39 3394475931Fax +06 30156999Email eleonora.nucera@policlinicogemelli.itAbstract: Gadolinium-based contrast agents (GBCAs) are considered to be safe, although sometimes patients report a hypersensitivity reaction when undergoing magnetic resonance imaging (MRI). The mechanisms of these reactions and of the sensitization to GBCAs are still largely unknown. We describe four cases of patients who experienced immediate adverse reactions to GBCAs with a demonstrated cutaneous hypersensitivity suggesting an IgE-mediated mechanism.Keywords: gadolinium-based contrast agents, hypersensitivity, IgE-mediated reactions

Lipid transfer proteins (LTPs) are widely widespread plant food allergens which represents the main cause of food allergy in adults living in the Mediterranean basin. The purpose of this study was to investigate in LTP patients the actual use of prescribed epinephrine auto-injector and appropriateness of its prescription. In addition, we investigated in these patients: (1) occurrence of new food reaction in the following three years after to diagnosis; (2) need and number of access to emergency services; (3) presence of possible predictive factors to further food reactions. One-hundred sixty-five adult patients sensitized to LTPs have been included. During follow-up, we recorded 68 further reactions, most of them (77.9%) characterized by local symptoms; rarely the patients required an emergency-department visits (16.1%) and only one patient (1.7%) used the epinephrine auto-injector. The patients with a previous history of anaphylaxis at baseline turned back to access to emergency services also during the follow-up (p = 0.006). The majority of patients with recorded systemic reactions (p = 0.004) and treated in an emergency room (p = 0.028) did not have any co-factor-enhanced at diagnosis. We noted an association between platanus pollen sensitization and severity of further reactions during the follow-up (p = 0.026). Epinephrine auto-injector were prescribed to 108/165 patients (65.5%) with an over-prescription rate of 25%. The unforeseeable clinical presentation of LTP allergic reactions and the eventual role played by the cofactor make necessary schedule a follow-up to monitor the patients over time and to assess the actual use of epinephrine auto injectors prescribed.

BACKGROUND/OBJECTIVES: Several scoring systems have been specifically developed for risk stratification in COVID-19 patients. DESIGN: We compared, in a cohort of confirmed COVID-19 older patients, three specifically developed scores with a previously established early warning score. Main endpoint was all causes in-hospital death. SETTING: This is a single-center, retrospective observational study, conducted in the Emergency Department (ED) of an urban teaching hospital, referral center for COVID-19. PARTICIPANTS: We reviewed the clinical records of the confirmed COVID-19 patients aged 60 years or more consecutively admitted to our ED over a 6-week period (March 1st to April 15th, 2020). A total of 210 patients, aged between 60 and 98 years were included in the study cohort. MEASUREMENTS: International Severe Acute Respiratory Infection Consortium Clinical Characterization Protocol-Coronavirus Clinical Characterization Consortium (ISARIC-4C) score, COVID-GRAM Critical Illness Risk Score (COVID-GRAM), quick COVID-19 Severity Index (qCSI), National Early Warning Score (NEWS). RESULTS: Median age was 74 (67-82) and 133 (63.3%) were males. Globally, 42 patients (20.0%) deceased. All the score evaluated showed a fairly good predictive value with respect to in-hospital death. The ISARIC-4C score had the highest area under ROC curve (AUROC) 0.799 (0.738-0.851), followed by the COVID-GRAM 0.785 (0.723-0.838), NEWS 0.764 (0.700-0.819), and qCSI 0.749 (0.685-0.806). However, these differences were not statistical significant. CONCLUSION: Among the evaluated scores, the ISARIC-4C and the COVID-GRAM, calculated at ED admission, had the best performance, although the qCSI had similar efficacy by evaluating only three items. However, the NEWS, already widely validated in clinical practice, had a similar performance and could be appropriate for older patients with COVID-19.

Background: Vaccines are very effective medical tools for disease prevention and life span increase. Controversies have raised concern about their safety, from autism to polio vaccine contamination with simian virus 40 (SV-40). Hysteria surrounding vaccine-associated risks has resulted in a declining number of vaccinations in developed countries. Outbreaks of vaccine-preventable diseases (e.g. measles) have occurred in Europe and North America, causing also some causalities. Objectives: In this review, data on safety and efficacy of vaccines are discussed, showing that the benefits of vaccines far outweigh the risks and that it is important to comply with vaccination protocols, to avoid spreading of severe, preventable diseases. Methods: Those opposed to vaccinations suggest that scientific literature supporting vaccines is influenced by pharmaceutical companies. In this review, studies on influenza produced by independent scientists and those authored by those who received some kind of benefit from the industry are discussed separately. All the chosen papers were selected through a MEDLINE research. Results: Vaccination rates are decreasing, even though they are effective public health tools. Influenza, for example, is responsible for 250,000–500,000 deaths each year, according to the WHO. Yet, campaigns to extend influenza vaccine to all elderly subjects report little success, because of the vaccine scare and because not all patients develop immunity following vaccination. Conclusions: This review proves that vaccine hysteria is detrimental because: 1) it causes an increased morbidity and mortality from preventable diseases; 2) it jeopardizes research for new vaccines; 3) patients are reluctant to accept any form of immune-therapy, commonly referred to as “vaccination”.

Midazolam is a short-acting benzodiazepine with central nervous system depressing action, commonly used for conscious sedation for various procedures and for its pharmacologic properties. In literature, severe adverse reactions to this drug are described, but only in few cases positive allergological tests were demonstrated. The authors collected herein five clinical cases of different allergic reactions to midazolam demonstrated by positive skin tests. The 1° case is a suspected Kounis syndrome with cardiorespiratory arrest during an elective video laparoscopic cholecystectomy. The 2° and 5° cases are two systemic reactions with involvement of the skin and the gastrointestinal/respiratory system during elective surgeries in two patients with clinical history of atopia, while the 3° and 4° cases are local skin reactions in correspondence with the infusion site of midazolam during the execution of a colonoscopy. All the patients performed a complete allergological evaluation for the reaction involved drugs. In all cases, only the intradermal test (IDT) with midazolam at 0.5 mg/mL was positive.Allergological tests performed in 10 healthy controls with negative results supported the diagnosis. Therefore, midazolam is often considered a safe drug, because it does not have any active metabolites, in rare cases, it could cause different types of allergic adverse reactions: from severe anaphylaxis with cardiorespiratory arrest to simple local skin reactions. Skin tests remain the first line in the diagnosis of an immediate-type hypersensitivity to midazolam; even if they could lose in sensitivity with increasing latency from the event. However the concentrations recommended by current guidelines of European Network for Drug Allergy (ENDA) and the European Academy of Allergy and Clinical Immunology (EAACI) drug allergy interest groups might not rule out some false-positive reactions due to an irritant effect that should be considered. In doubt cases, other allergological or laboratory tests (i.e., basophil activation tests, serum tryptase, or provocation tests) remain useful to support the diagnosis of an IgE-mediated reaction. Midazolam associated anaphylaxis is relatively rare and the risk factors associated with this event are actually unknown; however, it remains important to obtain a detailed allergic history and each surgical/endoscopic examination unit should be prepared to handle any situation or emergency that may occur.

Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 ± 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A ( p < 0.001), respiratory symptoms ( p < 0.001), anaphylaxis ( p = 0.003), hospitalizations ( p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.

Introduction The first therapeutic choice for food allergy is avoidance of the responsible food, but when this approach is not possible, specific oral desensitization could be considered as a good alternative. It is not clear yet whether the acquired tolerance is transient or persistent. Aim We report on a subset of 13 patients of a larger study, treated successfully with specific oral tolerance induction who experienced secondary loss of tolerance after a period of allergen avoidance. Material and methods Thirteen patients affected by IgE-mediated food allergy: to cow milk (3 patients), to hen egg (3 patients), to cod fish (2 patients), to peanuts (1 patient) and to corn (1 patient) confirmed by a complete allergological workup and a double-blind placebo-controlled food challenge (DBPCFC), were treated with sublingual-oral desensitization. After the interruption of the maintenance phase, the laboratory tests were performed and 12 of 13 patients underwent DBPCFC. Results Oral specific desensitization was completed successfully in all the 13 reported patients. At different times after the end of treatment, they decided, on their own initiative, to stop the ingestion of incriminated food. A new food allergen re-exposure caused adverse reactions in 12 of 13 patients. The detection of specific IgE and IgG4 during the period of allergen avoidance showed an increase in or a stable level of specific IgE and a decrease in specific IgG4 in 8 patients. Conclusions According to our experience, the tolerance obtained through the desensitizing treatment is transient and so the regular allergen intake is necessary for its maintenance.

Introduction The only etiological and decisive therapy, able to influence the natural history of latex allergy is the specific desensitization. Aim To verify the clinical efficacy and immunological changes determined by latex sublingual immunotherapy in allergic patients who underwent this treatment for at least 3 years. Material and methods We enrolled 76 patients (16 males and 60 females, mean age 34 years old) with evidence of a natural rubber latex allergy. To assess the effectiveness of the immunotherapy we performed a latex skin prick test, specific IgE and IgG4 and challenge tests before and after at least 3 years of desensitization. Results We observed a reduction in the mean diameter of the wheal area at the skin prick test and a decrease in latex specific IgE while no significant changes of latex IgG4 values were found. Moreover a reduction of symptoms and scores at the provocation tests were remarked. Conclusions Although the primary prevention (which still remains the gold standard treatment for patients suffering from the latex allergy) sublingual immunotherapy can be offered with efficacy in addition to symptomatic treatment to selected patients.

LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15986

The eosinophilic oesophagitis (EoE) is a chronic immune/antigen disorder of the oesophagus clinically characterized by dysphagia and pathologically by mucosa eosinophilic infiltration. Th2-type allergic reactions are considered having important roles in the aetiopathogenesis of EoE. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the oesophagus are the most important treatments. ‘Systemic nickel allergy syndrome’ (SNAS) interests about 20% of patients with nickel contact allergy which could present systemic cutaneous manifestations (urticaria, oedema, etc.) and also respiratory and digestive symptoms (meteorism, abdominal pain, diarrhoea, etc.). In the literature, it is demonstrated that nickel oral immunotherapy is effective in reducing symptoms of SNAS and in modulating inflammatory parameters. We describe the case of a 48-year-old woman suffering from EoE not responsive to the topical steroid administration and diagnosis of SNAS. The patient started nickel oral desensitization according to the literature protocol continuing nickel-free diet. After 1 year from the beginning of the treatment, during the maintenance dose (500 ng three times a week), she decreased gradually the dosage of immunotherapy and reintroduced all the culprit foods. After the immunotherapy interruption, during the free diet, she repeated the oesophagogastroscopy with a complete macroscopic and histological resolution. We showed the first case of an EoE in a patient affected by SNAS responsive to the nickel-free diet and the oral immunotherapy.

The role of profilin as an allergen has long been questioned. The capacity of profilin to induce respiratory symptoms has recently been demonstrated; moreover, over 50% of patients sensitized to profilin experienced symptoms after the ingestion of plant-derived foods, suggesting that profilin should be considered as a clinically relevant food allergen. We describe the cases of seven allergic patients with oral allergy syndrome and other adverse reactions after eating plant-derived food, that have been undergone to profilin desensitization treatment. The protocol started with a drop of profilin solution (50 µg/mL) diluted 1:1018 in water until the highest dose of 10 drops of undiluted solution three times a week. At the end of the treatment we observed a decreased mean diameter of profilin wheal in skin prick test (SPT) in five of the seven participants and in profilin specific IgE values in six patients that repeated the test. Regarding basophil activation test (BAT) and the detection of IgG4, we do not have significant results because the tests have to be repeated in some patients. Regarding the double-blind placebo-controlled challenges, after about 10 months of induction phase all the patients showed tolerance to several foods that they previously did not tolerate. Moreover, the immunotherapy with profilin has proved to be safe because no serious adverse events have been reported in our patients. In summary, the results of this exploratory study of sublingual immunotherapy (SLIT) for profilin allergy show that it can be a promising therapeutic option that could modify the clinical reactivity of the patients to the intake of plant-derived food.

Nickel (Ni) oral hyposensitization treatment (NiOHT) is an effective management approach for Ni allergy. No health-related quality of life (HRQoL) data exist for the pre- and post-treatment with NiOHT in systemic nickel allergy syndrome (SNAS). The aims of this study were (a) to explore HRQoL in SNAS patients, (b) to assess changes of HRQoL after 1 year of NiOHT; (c) to evaluate psychological status of patients. SNAS patients completed the Short-Form 36-Item Health Survey and Psychological General Well-Being Index before and 1 week after the end of NiOHT. Moreover, psychological state was assessed with the Minnesota Multiphasic Personality Inventory (MMPI-2). A total of 52 patients self-reported pre- and post-treatment questionnaires. HRQoL was poor at baseline. After 1 year of NiOHT, all outcome measure scores improved by about 20% with respect to baseline data ( P

INTRODUCTION: Lipid transfer proteins (LTP), profilin and PR-10 are the most important panallergens in central and southern Italy. Lipid transfer proteins are stable molecules, predominantly present in the fruit peel, which can induce systemic symptoms after ingestion of vegetables. Profilin and PR-10 are randomly distributed in the pulp and peel. Both are labile proteins and usually determine reactions restricted to the oral cavity. Panallergens-specific IgE may cross-react with homologues from different plant sources, due to their conserved structure. AIM: To assess the pattern of sensitization to panallergens and the correlation with the clinical history and the allergological evaluation of food and aeroallergens. MATERIAL AND METHODS: One hundred and twenty patients with adverse reactions after vegetables ingestion underwent skin prick tests (SPT) with commercial extracts of plant-derived foods and inhalant allergens and commercial extracts of LTP, profilin and PR-10. RESULTS: Many patients presented positive SPT with different plant-food allergens. We found that 76 patients were sensitized to LTP, 14 to profilin and 5 to PR-10. In the LTP-sensitized group, 64 (84%) patients suffered from systemic symptoms while the patients sensitized only to profilin referred the oral allergy syndrome. CONCLUSIONS: This study shows a high rate of sensitization to LTP in our population according to the literature about food allergy in our geographical area and confirms the literature data about the symptoms referred by patients with sensitization to panallergens. Panallergens should be considered as clinically relevant food allergens.

Background/Aims Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain or discomfort accompanied by abnormal bowel movements. In sensitized subjects, ingested nickel (Ni) may induce gastrointestinal symptoms similar to IBS, in addition to typical systemic cutaneous lesions (systemic nickel allergy syndrome [SNAS]). A low nickel diet could improve the systemic manifestations. We evaluated prevalence of nickel allergy in IBS and effects of low Ni diet on (1) gastrointestinal symptoms control, (2) intestinal barrier function, (3) quality of life, and (4) psychological status of patients with IBS and Ni-sensitized patients. Methods Twenty consecutive patients affected by IBS and suspected SNAS underwent intestinal permeability tests. Gastrointestinal symptoms were evaluated using the visual analogue scale before and after 3 months low Ni diet. Subjects with increased intestinal permeability at baseline repeated nuclear examination after the diet. Results The most frequent profile was diarrhea-predominant IBS (8/20). The low Ni diet induced a significant and constant improvement of gastrointestinal symptoms and an equally significant improvement of visual analogue scale. Mean urinary output of ⁵¹Chromium ethylene-diamine-tetra-acetate (⁵¹Cr-EDTA) was 5.91%/24 hr (± 2.08), significantly different from the control group (2.20%/24 hr ± 0.60, P < 0.0001). Conclusion This pilot study shows that low Ni diet improves gastrointestinal symptoms in patients with IBS and SNAS.

During pregnancy thrombo-prophylaxis could be required in high risk women. If a severe allergic reaction to low-molecular-weight-heparin (LMWH) or a heparin-induced-thrombocytopenia (HIT) occurs, it's mandatory to stop the drug. Fondaparinux could be an effective option. In the present review, the maternal and pregnancy outcomes of 65 pregnancies in women using Fondaparinux were reported. It was well-tolerated and rate of pregnancy complications was similar to that observed in general population. Regarding congenital malformations, further studies are necessary to investigate the safety of the drug.

Background and objective Administration of carbapenems to β-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated β-lactam allergy. Patients and methods We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to β-lactams. The inclusion criteria were a positive skin test result to at least 1 β-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several β-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. Results We examined 49 patients with a clinical history of immediate reactions to β-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 β-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. Conclusions The practice of avoiding carbapenems in patients with β-lactam allergy should be abandoned considering the very low rate of cross-reactivity. β-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability.

The multiple drug intolerance syndrome is a clinical entity characterized by adverse drug reactions to at least three drugs, chemically, pharmacologically and immunogenically unrelated, manifested upon three different occasions, and with negative allergy testing. Symptoms referred by the patients are often subjective, of neurovegetative origin. The aim of the study is to characterize patients suffering from the multiple drug intolerance syndrome from a psychological point of view, and to compare them to healthy subjects. We studied 30 women suffering from the multiple drug intolerance syndrome. All subjects underwent the following psychodiagnostic tests: (1) the State Trait Anxiety Inventory-Form Y, (2) the Zung Self-rating Anxiety Scale, (3) the Zung Self-rating Depression Scale, (4) the Quality of life enjoyment and satisfaction questionnaire, (5) the Minnesota Multiphasic Inventory-2, (6) the Toronto Alexithymia Scale. The study group was compared to 30 healthy women. When compared with the control group, our patients showed: a higher anxiety, a higher grade of depression, this difference was statistically significant (p < 0.01); a high difference (p < 0.01) between the two groups as regards somatic symptoms; a higher grade of alexithymia (p < 0.01); and a worse quality of life, in all the analyzed ambits. These findings clearly demonstrate the importance of psychological symptoms in patients with the multiple drug intolerance syndrome, and show that a complex allergy and psychological work-up is mandatory in the management of these patients.

Background: Cross-reactivity between aztreonam and β-lactams is poor, but tolerability of aztreonam has been assessed in a few groups of patients suffering from IgE-mediated allergy to β-lactams. The aim of this study was to assess the cross-reactivity of aztreonam with other β-lactams and its tolerability in patients with cell-mediated allergy to these drugs. Methods: We studied 78 patients with cell-mediated allergy to β-lactams who underwent skin prick, immediate and delayed-reading intradermal tests as well as patch tests with penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins, cephalosporins, aztreonam and imipenem. Patients with negative allergy testing with aztreonam underwent an intramuscular test dosing and were observed for 3 h. Results: Our patients experienced 94 non-immediate reactions; delayed-onset urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema (15 cases) and itching erythema (13 cases) were the most reported symptoms. Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were the most involved drugs. All patients had a positive patch test and/or a positive delayed-reading intradermal test to at least 1 β-lactam antibiotic and none had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65 patients underwent intramuscular test dosing with aztroenam, and none of them had a clinical reaction. Conclusions: Our data confirm the lack of cross-reactivity between β-lactams and aztreonam in patients with cell-mediated allergy to these drugs. Delayed-reading intradermal tests and patch tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in β-lactam-allergic patients.

Background: Administration of imipenem-cilastatin to patients with IgE-mediated hypersensitivity to β-lactams has always been considered potentially harmful. Recent studies have demonstrated the tolerability of carbapenems (imipenem-cilastatin and meropenem) in patients with IgE-mediated hypersensitivity to β-lactams; there are no studies on this topic regarding patients with cell-mediated allergy to β-lactams. The aim of this study is to assess cross-reactivity and tolerability of imipenem in patients with cell-mediated allergy to β-lactams. Methods: From our database we selected 73 patients with cell-mediated allergy to β-lactams, diagnosed by means of immediate-type skin tests, delayed reading intradermal tests, patch tests and detection of specific IgE. Patients with negative patch tests with imipenem-cilastatin underwent an intramuscular test dosing. Results: Our patients had a total of 94 nonimmediate reactions to penicillins. All patients had positive patch tests and/or delayed reading intradermal tests for at least one of the penicillin reagent tested and negative immediate-type skin tests and specific IgE. Four patients out of 73 had a positive patch tests to at least one penicillin reagent and imipenem-cilastatin showing cross-reactivity. Sixty-four patients underwent the imipenem-cilastatin intramuscular test dosing and none of them had a clinical reaction. Conclusions: Our rate of cross-reactivity between imipenem-cilastatin and other β-lactams was 5.5%. This result is different from previous findings and this may be explained by the fact that we investigated patients with cell-mediated allergy to β-lactams. Patients with cell-mediated allergy to β-lactams should undergo patch tests and a tolerance challenge test before treatment with imipenem-cilastatin.

Objective: The quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate-type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen-induced CD63 up-regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic. Materials and methods: Three male patients affected by cow’s milk allergy underwent successful oral desensitization to cow’s milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol. Results: Using a fluorescent enzyme immunoassay, the comparison of specific cow’s milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow’s milk proteins (a-lactoalbumin, b-lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases. Conclusions: Using flow cytometry, food allergen-specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance.

Nickel allergy is the most common contact allergy. Some nickel-sensitive patients present systemic (cutaneous and/or digestive) symptoms related to the ingestion of high nickel-content foods, which significantly improve after a specific low nickel-content diet. The etiopathogenetic role of nickel in the genesis of systemic disorders is, furthermore, demonstrated by the relapse of previous contact lesions, appearance of widespread eczema and generalized urticaria-like lesions after oral nickel challenge test. The aim of this study is to investigate the safety and efficacy of a specific oral hyposensitization to nickel in patients with both local contact disorders and systemic symptoms after the ingestion of nickel-containing foods. Inclusion criteria for the recruitment of these patients were (other than a positive patch test) a benefit higher than 80% from a low nickel-content diet and a positive oral challenge with nickel. Based on the previous experiences, our group adopted a therapeutic protocol by using increasing oral doses of nickel sulfate associated to an elimination diet. Results have been excellent: this treatment has been effective in inducing clinical tolerance to nickel-containing foods, with a low incidence of side effects (gastric pyrosis, itching erythema).

Summary Background Many efforts have been made to prevent nickel allergy, the most frequent contact allergy in industrialized countries, by identifying acceptable limits of exposure. Even though coins are not covered by the EU Nickel Directive, some authors suggest that nickel release from coins during handling may elicit contact dermatitis in nickel-allergic people. Objectives To evaluate sensitivity to nickel released from coins in nickel-allergic patients and to verify whether nickel release from the new Euro coins may elicit stronger cutaneous reactivity than from old Italian lire coins. Methods Twenty-five nickel-allergic patients were patch tested with 1- and 2-Euro coins, 1-, 2- and 50-Euro cent coins, and 100 and 500 Italian lire coins. Ten healthy nonnickel-allergic control individuals were also tested. Results Nineteen patients had positive patch tests to 1- and 2-Euro coins. One was also positive to 1- and 2-Euro cent coins, four to 50-Euro cent coins, and 13 to the 500-lire coin. None had a positive patch test to the 100-lire coin. The number and degree of positive patch tests to coins were related to nickel content. Conclusions Euro coins may be potentially more dangerous than old Italian coins. Coins containing little or no nickel should be chosen for coinage to prevent sensitization and to avoid exacerbation of contact dermatitis in nickel-allergic patients.

Lipid transfer proteins (LTP) constitute a family of proteins widely distributed through the plant kingdom [1]. Allergenic LTP have been identified in tree pollen and weeds, plant food allergen sources and latex. The primary sensitizer agent and the fruit mostly involved seems to be the peach [2]. Allergy to LTP has been mainly described in Italy, Spain and Greece [3] and only exceptionally in the Central and Northern Europe. The allergenic potential of LTP is influenced by their localization and stability to proteolytic and thermal denaturation: indeed LTP are stable molecules, predominantly present in the fruit peel; it might explain why some LTP-sensitized individuals easily tolerate fruits without peel [4, 5]. Due to its heat and pepsin-resistance, LTP may determine local symptoms such as the oral allergy syndrome and systemic symptoms up to anaphylaxis after the ingestion of fruits and vegetables [6]. Previous studies documented the connection among hypersensitivity to LTP and reactions to nonsteroidal anti-inflammatory drugs (NSAIDS) [7]. We describe the case of a patient, a 33-year-old woman with generalized urticaria and angioedema thirty minutes after eating a veal steak and lettuce; after lunch she also took an oral film of ketoprofen for headache. Skin prick tests (SPT) with commercial extracts of many plant foods (garlic, peanut, rice, pear, tomato, walnut, hazelnut, apple, peach, banana, onion, wheat, yeast, corn, barley, potato, celery, soy and spinach) were performed. The patient had positive SPT to apple, hazelnut, peach, soy and celery and specific IgE positive (> 0.35 U/ml) only to apple (0.83 U/ml), peach (1.70 U/ml) and hazelnut (3.73 U/ml). The patient told us she did not eat currently these foods because previously she presented oral allergy syndrome (which includes itching and swelling of the lips, palate and tongue) after their ingestion. SPT (Alk-Abello, Milan, Italy) with the commercial extracts of LTP and profilin were performed: only LTP was positive; we also detected specific IgE (UniCAP, Phadia, Uppsala, Sweden) for the recombinant allergen Pru p 3 whose value was 0.44 U/ml. Moreover SPT and patch test with ketoprofen were negative. Before the reaction she had already taken ketoprofen without symptoms but she had never associated the intake of this drug with the ingestion of lettuce (which is one of the plant foods-containing LTP). When she came to our attention she had already reintroduced veal steak in her diet without presenting reactions. On the basis of these results we decided to perform an oral test with ketoprofen oral film 80 mg: we diluted the drug in 10 ml of water and we administered increasing doses of this solution every 30 min (1 ml, 2 ml, 3 ml and 4 ml of the solution). The patient was monitored during this procedure and for 3 h after the last administration. No symptoms occurred during the test and the patient tolerated the recruitment of ketoprofen also at home. Then she underwent an oral challenge with lettuce: this test was performed in 2 days in the day hospital regimen by administering increasing doses of lettuce starting from 1 mg of lettuce until reaching the dose of 100 g of this food. Challenge was negative and then the patient tolerated lettuce also at home. This case report shows an important association between hypersensitivity to LTPs and reactions to NSAIDS as reported in other works [7, 8]. Although the association between hypersensitivity to lipid transfer protein and the onset of reactions after taking NSAIDS is only a recent observation, in these months we are evaluating other patients referred to our Allergy Unit with a history similar to that of the patient described in our case report. In particular we point out to the cases of 2 other patients: a patient with urticaria-angioedema after the ingestion of lettuce followed by the intake of ketoprofen; a patient with urticaria after the ingestion of sunflower seeds followed by the intake of ketoprofen. Both these patients, at the time of the visit, had taken again (but separately) ketoprofen and the foods involved in the reactions by themselves without presenting symptoms. On the basis of these observations we think that the association between hypersensitivity to lipid transfer protein and reactions after taking NSAIDS is not casual but it implies a pathogenic mechanism on which we are currently working. In the past Asero [7] showed that LTP allergic patients had a > 4 times more frequent history of NSAIDS hypersensitivity than atopic controls. In agreement with previous studies, we hypothesize that NSAIDS might be co-factors in the clinical expression of food allergy by the dysregulation of the epithelial barrier and the increase of the permeability of the gut mucosa: as a result of that, food allergens more easily interact with the patient's immune system. It is known that certain augmenting factors (NSAIDS, physical exercise and alcohol) may be clinically relevant for some patients [9, 10]: in the case of a suggestive history but a negative oral challenge, one should consider the possible involvement of augmenting factors, always ask for possible augmentation and other risk factors during the recent past [11]. At the moment, on the basis of previous studies and our experience, we recommend to patients sensitized to LTPs avoiding the ingestion of vegetables containing this panallergen during therapy with NSAIDS. Further investigations are needed to confirm our hypothesis but we believe that these new aspects of the allergic reactions represent an impressive backdrop on which to act in the near future.

Summary Background : The possibility of inducing oral desensitization in patients with food allergy is still controversial and no standardized programmes are yet available. Aim : To evaluate the safety and efficacy of oral desensitization in patients with allergy induced by the most common food allergens. Methods : Fifty-nine patients with food allergy underwent an oral desensitizing treatment according to standardized protocols. The control group consisted of age- and sex-matched subjects, who followed a strict elimination diet. Specific immunoglobulin E and immunoglobulin G4 were assessed at baseline and after 6, 12 and 18 months. Results : The majority of patients (83.3%) successfully completed the treatment. During treatment, 51.1% of subjects experienced some mild side-effects, easily controlled by the oral administration of antihistamines or sodium cromolyn. Specific immunoglobulin E showed a significant decrease, whilst specific immunoglobulin G4 showed a significant increase in all patients. Conclusions : The immunological findings induced by oral desensitization in food allergy allow us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory allergies. Moreover, the proposed standardized oral desensitization protocols may represent an effective alternative approach in the management of food-allergic patients.

UNLABELLED The prevalence of latex allergy has rapidly increased. Clinical manifestations range from contact urticaria-angioedema and rhinoconjunctivitis to more severe bronchial asthma and anaphylactic shock. The only effective therapy is desensitization. We studied 24 patients allergic to latex: 12 of them underwent a rush (4-day) sublingual desensitization to latex, performed by putting increasing doses of latex extract under the patients' tongues for 3 min every 20 min, followed by a maintenance therapy. The other 12 patients were considered controls. The sublingual rush desensitization protocol was successfully completed in all patients with no side effects. After 3 mo, all patients underwent an allergological evaluation, which showed a significant improvement of symptoms scores after challenges in the treated group as compared with the controls. All the desensitized patients can now wear latex gloves and undergo medical procedures without any symptoms. IMPLICATIONS We present 12 cases of latex allergy in patients who underwent desensitization by a sublingual exposure protocol. This study provides evidence that a safe therapeutic approach to latex allergy is possible.

Two clinical reports dealing with subcutaneous desensitization to latex are available, but these treatments were reported to have significant side effects. To investigate an alternative method for latex desensitization, we present five cases of immunoglobulin E-mediated latex allergy in which a specific desensitization was successfully performed by means of an original exposure protocol. Five female patients with proven latex allergy underwent an original contact desensitization by wearing latex gloves daily, progressively increasing exposure to latex. All patients reached a final latex exposure time of 60 min in both hands. The desensitization protocol was completely successful in all patients. Twelve months after the beginning of the desensitization program, all the treated subjects were able to wear latex gloves daily without any clinical manifestations. This study provides evidence that a successful contact desensitization to latex is possible with no side effects. The adopted exposure protocol seems to be completely safe and effective. However, further studies in larger groups of subjects are necessary to fully confirm these preliminary results.We present five patients with latex allergy who underwent desensitization by a new cutaneous exposure protocol. This study provides evidence that a safe therapeutic approach to latex allergy is possible.

Introduction Lipid transfer proteins (LTP), profilin and PR-10 are the most important panallergens in central and southern Italy. Lipid transfer proteins are stable molecules, predominantly present in the fruit peel, which can induce systemic symptoms after ingestion of vegetables. Profilin and PR-10 are randomly distributed in the pulp and peel. Both are labile proteins and usually determine reactions restricted to the oral cavity. Panallergens-specific IgE may cross-react with homologues from different plant sources, due to their conserved structure. Aim To assess the pattern of sensitization to panallergens and the correlation with the clinical history and the allergological evaluation of food and aeroallergens. Material and methods One hundred and twenty patients with adverse reactions after vegetables ingestion underwent skin prick tests (SPT) with commercial extracts of plant-derived foods and inhalant allergens and commercial extracts of LTP, profilin and PR-10. Results Many patients presented positive SPT with different plant-food allergens. We found that 76 patients were sensitized to LTP, 14 to profilin and 5 to PR-10. In the LTP-sensitized group, 64 (84%) patients suffered from systemic symptoms while the patients sensitized only to profilin referred the oral allergy syndrome. Conclusions This study shows a high rate of sensitization to LTP in our population according to the literature about food allergy in our geographical area and confirms the literature data about the symptoms referred by patients with sensitization to panallergens. Panallergens should be considered as clinically relevant food allergens.

Cutaneous reactions to thalidomide have been noted in approximately 46% of patients treated with this drug. We describe a case of a 65-year-old woman with multiple myeloma who developed fever and a generalized, itchy maculopapular rash after a 2-day treatment with thalidomide 100 mg orally. Skin prick and patch test results with thalidomide were negative, while the oral provocation test results were positive. Because thalidomide was necessary for the patient, she underwent an oral desensitization protocol, and on the fifth day, she could tolerate 100 mg of oral thalidomide. To our knowledge, this is the first report in the literature regarding this topic.

Keywords: α-lipoic acid; dietary supplement; drug hypersensitivity; type IV allergic reaction

Natural rubber latex allergy (NRL-A) is an international problem of public health. About 50-60% of NRL-A patients may present adverse reactions after ingestion of cross-reacting vegetable foods. This condition, called "Latex-fruit Syndrome", is a matter of research. The aim of our study is to distinguish between clinical/subclinical latex-fruit syndrome and cross-sensitization to latex and food/pollen allergens on the basis of latex recombinant allergens. We studied 51 patients with food hypersensitivity and serological evidence of NRL sensitization. The subjects underwent an accurate allergological evaluation (skin prick test with latex, food and pollen extracts, specific IgE to latex and recombinant allergens, challenge provocation tests). The patients were divided in two groups: group A) 34 patients with clinical and serological latex and fruit/vegetable allergies; group B) 17 patients allergic to fruits/vegetables and/or pollens, with serological, but not clinical NRL-A. All the latex challenge tests resulted positive in group A patients and only two patients of group B presented positive cutaneous challenge tests. Moreover, specific IgE-antibodies were detected to rHev b 5, to rHev b 6.01, to rHev b 6.02 and to rHev b 8 (and other profilins) of group A patients, while in group B we observed a monosensitization to Hev b8, probably linked to a cross-sensitization to pollens and foods. At the present state of knowledge, we need a multi-parametric approach based on a combination of clinical history, diagnostic tests (CRD) and latex challenge tests to make diagnosis of latex-fruit syndrome.

Food allergy is a matter of concern because it affects about 0.5–3.8% of the paediatric population and 0.1–1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. The treatment of food allergy is still a matter of debate. Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis), epinephrine, are the drugs of choice for the treatment of symptoms of food allergy. Sodium cromolyn may be used prophylactically even though there are no controlled studies certifying its efficacy. The only etiologic treatment of food allergy is specific desensitization. Sublingual-oral-specific desensitization has been used by our group for the treatment of food-allergic patients with a high percentage of success.