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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.

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.

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.

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

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.

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.

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.

Adverse reactions to folic acid are an extremely uncommon condition; we present three cases of hypersensitivity to folic acid with different symptomatic manifestations. In the first and second cases, we made the diagnosis of IgE-mediate-type allergy to folic acid, while in the third one, we found a fixed drug eruption to folic acid.

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.

Profilins constitute a family of highly conserved proteins, which are present in all eukaryotic cells and are involved in processes related to cell motility. The first allergenic profilin was described in birch pollen and was designated Bet v 2. Allergenic profilin were identified in tree and grass pollens, in weeds, in plant-derived foods, as well as in latex. Due to conserved structure of the profilins, specific IgE may cross-react with homologues from virtually every plant source. Therefore, profilin sensitization is a risk factor for allergic reactions to multiple pollen and food allergen sources. Profilins are randomly distributed in pulp and peel and they are labile to heat denaturation and pepsin digestion. In fact the ingestion of vegetables in profilin sensitized patients usually determines reactions restricted to the oral cavity (oral allergy syndrome, OAS), despite in literature systemic reactions to zucchini and litches are reported. We describe the history of six patients with adverse reactions after eating plant-derived food and positive allergological evaluation (skin tests, specific IgE, basophil activation test and double-blind placebo-control challenges (DBPCFC) for profilin, that have been undergone to desensitization treatment. The protocol of desensitization 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. They underwent this desensitization treatment at home and were followed in Day Hospital regimen monthly. According to the protocol they were trained in medical treatment of allergic reactions and equipped with an emergency kit: autoinjectable epinephrine, betamethasone and clorphenamine. At the end of the treatment all patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Moreover, the desensitization with profilin has proved to be safe as no serious adverse events were observed in our patients. Profilin desensitization allowed that our patients could manage their diet without restriction, eating several foods previously not tolerated.