Anna Giulia Ricci

The interhemispheric transcallosal-transversal approach to the lesions of the anterior and middle third ventricle: Surgical validity and neuropsychological evaluation of the outcome

Based on the observation of the course of callosal fibres and of their artero-venous support as appearing in a microanatomic study, the Authors propose a variant of standard callosotomy procedure by the introduction of the transverse section of callosal fibres. This technique would allow the surgeon to spare a larger number of callosal fibres by the combined effect of a lower direct mechanical traction on fibres and a lower impact on artero-venous microcircle. The neuropsychological outcome of the patients who underwent this kind of procedure was evaluated. Fourteen patients affected by occupying-space lesions involving the anterior and middle third ventricle were included in the study. Ten patients underwent transverse callosotomy, four subjects received standard sagittal callosotomy. A control group was also included in the study. All patients underwent a pre-operative and six months post-operative neuropsychological evaluation focused on performance at cognitive and attentional tasks. No disturbances in executive function were observed in either group. Patients receiving transverse callosotomy performed as well as control group subjects in attentive tasks, which is not the case of patients undergoing sagittal callosotomy who show a marked deficit in selective attention for left side visual field. The observed more favourable neuropsychological outcome supports transverse callosotomy as a valid alternative method to standard longitudinal callosotomy in third ventricle surgery.

Profilin Desensitization in Two Patients with Plant-Derived Food Allergy

Profiling are “panallergens”, responsible for many cross-reactivities between inhalant, latex and plant-derived food allergens. We evaluated the effectiveness and the safety of sublingual desensitization treatment (SLIT) in two patients with allergic respiratory and food diseases. Skin prick tests, IgE and IgG4 assays to pollens, some plant-derived foods, profilin, non-lipid specific transfer protein and PR 10 proteins were performed. The patients also underwent double-blind placebo-controlled challenge (DBPCFC) with the culprit foods and profilin and then a SLIT with it. Both the patients had positive SPT, specific IgE and DBPCFCs with profilin and some vegetables referred in anamnesis. They therefore underwent SLIT with profilin extract. At the end of treatment, the patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Profilin desensitization allowed our patients to manage their diet without restriction, eating several foods previously not tolerated.

Utility of Basophil Activation Test for monitoring the acquisition of clinical tolerance after oral desensitization to cow’s milk: Pilot study

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 (α-lactoalbumin, β-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.

Sublingual immunotherapy with natural rubber latex: a case report with 8‐year follow‐up

We report a patient who successfully underwent sublingual latex immunotherapy and who has been followed-up for 8 years. Since the 1970s, type I allergy to natural rubber latex (NRL) has been a public health problem (1). Symptoms of NRL allergy range from contact urticaria and asthma to anaphylaxis. They are elicited by direct contact with NRL items (e.g. medical devices) or by inhalation of airborne latex proteins. Proper diagnosis of latex allergy is important for appropriate preventive measures and treatment.

The clinical meaning of positive latex sIgE in patients with food/pollen adverse reactions.

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.

Adverse reactions to nonsteroidal anti-inflammatory drugs and hypersensitivity to lipid transfer proteins

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 patients 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.

Specific oral immunotherapy in food allergic patients: transient or persistent tolerance?

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.

Hypersensitivity to major panallergens in a population of 120 patients

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.

Profilin desensitisation in patients with adverse reaction after plant-derived: our experience

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.

Role of basophil activation test for monitoring the immunological changes during desnsitization to cow’s milk: a case report

The basophil activation test (BAT) has proven to be a useful tool for the diagnosis of IgE-mediated food allergy and the evaluation of clinical tolerance in food allergic patients. Until now, successful oral desensitization to food allergen has been correlated with changes in cytokine production (IL-4 and INF-γ) and allergen-specific IgE and IgG4 antibodies. We report a case of a 12-year-old male affected by cow’s milk allergy. The diagnosis was based on a positive allergological work-up, included skin prick test with commercial food extracts (Alk-Abello) and fresh cow’s milk (prick-by-prick method), detection in serum of total and specific IgE (ImmunoCAP System, Phadia), basophil activation test and finally a double-blind placebo-controlled food challenge. Skin prick test, specific IgE, BAT and oral food challenge were positive and so we decided to carry on a sublingual-oral desensitization treatment with cow’s milk, performed according to standardized protocol. In order to evaluate the immunological changes occurred during the immunotherapy, we performed further laboratory tests, included the detection in serum of total and specific IgE and BAT at the end of protocol. Desensitization was successfully carried out within 12 months, reaching the maximum dose of 150 ml of cow’s milk without side effects. The patient showed a decrease of specific IgE levels without reaching normal values and an increase of specific IgG4 levels; whereas the BAT starting from a positive value of 59% became negative after 12 months of treatment. This case report shows how it is possible to monitor allergen-specific basophil responses using the flow cytometry in order to identify an acquired tolerance induced by desensitization. Although further studies are needed, it was interesting to note that the basophil activation test seems to be more sensitive and characterized by a close correlation with the clinical tolerance.