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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 1:1018in 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.

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.

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 IgG4assays 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.

AvidinOX® a product containing aldehyde groups, generated by ligand-assisted sugar oxidation of avidin by sodium periodate, maintains the capacity to bind biotin with very high affinity and exhibits the property to chemically link cellular and tissue proteins through Schiff's base formation thus residing in tissues for weeks. In recent studies, we have shown that AvidinOX exhibits much higher persistency in the skeletal muscle than native avidin. The aim of the present study is to evaluate whether AvidinOX-biotin interaction might be exploited to target biotinylated cells to an AvidinOX pre-treated muscle. To accomplish this we performed the following experiments: 1) The proliferation and differentiation properties of biotinylated C2C12 myoblasts were tested in vitroupon linkage to AvidinOX; 2) Bone marrow-derived cells (BMDC) were isolated from GFP positive transgenic mice [strain C57 BL/6-tg (UBC-GFP)] and after biotinylation (bBMDC) were intravenously administered to naive and MAVA+ (Mouse anti Avidin Antibody) C57/B6 mice previously injected with AvidinOX in a tibial muscle (TM). Localization efficiency of GFP+bBMDC was evaluated on serial sections of the AvidinOX- and vehicle-treated (contra lateral limb) TM, 5 days after transplantation. Results show that biotinylated C2C12 cells, once linked to AvidinOX, maintain their proliferation and differentiation capacity, in vitro. Intravenous injection of biotinylated GFP+bone marrow-derived cells leads to their specific and efficient localization in the AvidinOX-pre-treated, but not contra lateral muscle of both naive and MAVA+mice. The present data suggest a potential use of AvidinOX to improve tissue targeted delivery of biotinylated cells.

Adverse drug reactions (ADR) are an important medical problem. The aim of this study is to investigate the clinical characteristics of children with ADR and to assess the tolerability of alternative drugs in children (under 16 yrs of age) with a history of ADR. We studied 278 children (132 males and 146 females). Patients were studied by recording personal history and performing in vivoskin testing, in vitrolaboratory tests and challenge tests. Patients who had experienced mild adverse reactions underwent challenge tests without any premedication; patients with a clinical history of moderate reactions, received a premedication with sodium cromolyn 30 min before the oral challenge; patients with a clinical history of severe reactions or undergoing parenteral challenges, were given an antihistamine 30 minutes before. A total of 660 adverse events were reported with 126 different drugs involved. Antimicrobial agents were the most involved drugs (51.7%). Non-steroidal anti-inflammatory drugs were involved in 22.7% of episodes. The most reported symptoms were cutaneous. Allergy testing was negative in 272 patients. A diagnosis of drug allergy was reported for 6 patients. A total of 669 challenge tests were performed. 639 were negative at first attempt while 22 were positive. Eight were repeated using a different premedication and resulted negative. Hypersensitivity drug reactions in children are mainly non-allergic. A premedication with sodium cromolyn or with oral H1-antihistamines may be useful in preventing ADR.

The aim of this study is to evaluate the sensitivity, specificity and safety of challenge tests and their usefulness in the diagnosis of latex allergy. Forty adult subjects (F/M = 34/6, aged 18–66 yrs) with a history of adverse reactions after latex exposure and positive prick test and/or specific IgE to latex were enrolled. They were compared with 20 control subjects. They underwent provocative (cutaneous, mucous-oral, sublingual, conjunctival, nasal, bronchial, vaginal) tests. Symptoms and drug scores were recorded for each patient during challenges. All patients reacted to at least one of the following: cutaneous, nasal and conjunctival tests. No systemic reactions requiring epinephrine occurred. Of the challenges, the vaginal test resulted as the safest, but it had low sensitivity and many limits related to the procedure. According to our data, bronchial and nasal tests had the highest sensitivity (76% and 82% respectively), and were more precise than other tests in determining latex exposure and symptoms, but the bronchial test also presented the highest rate of risk. Mucous and cutaneous tests resulted as the most reliable. For all the tests, specificity and positive predictive value were 100%. All control subjects resulted negative to all challenges. There were no statistically significant changes in skin and serologic tests between the first and second visits. Correlations between MIS and skin tests and between MIS and serum tests were not found. Challenges can be considered safe diagnostic procedures. Tests that most faithfully reproduce natural exposure, on the basis of a patient's history, are preferable.

The aim of this paper is to assess in an open prospective pilot case-control study the tolerability, safety and efficacy of an ultra-rush sublingual immunotherapy (SLIT) protocol with Vespulavenom in wasp allergic patients compared to subcutaneous immunotherapy (SCIT). Forty-one wasp allergic patients were treated with sublingual (SLIT group) or subcutaneous (SCIT group) ultrarush immunotherapy with Vespulavenom extract. All patients underwent skin tests and serum specific IgE and IgG4detection before enrolment and after 6, 12 and 24 months of immunotherapy. The SLIT group consisted of 21 (6 females and 15 males) patients who received increasing doses of Vespulavenom (Aquagen, ALK-Abelló) until the final dose of 30 drops of extract in 3 hours, containing 100,000 SQ-U/ml. The maintenance dose was of 10 drops of pure venom extract 3 times a week, for a total dose of 100,000 SQ-U weekly (corresponding to 100 μg of venom extract). The SCIT group consisted of 20 patients (16 males and 4 females) who were treated with subcutaneous ultrarush immunotherapy with Vespulavenom extract (Pharmalgen, Alk-Abelló). Patients received 101.1 μg of Vespulavenom in 3 hours and were treated with 100 μg of wasp venom monthly. During the ultrarush sublingual treatment 2 patients (9.5%) experienced mild side-effects. Specific IgE and specific IgG to wasp venom did not show any significant modification. Four patients were field-stung by a wasp during the treatment (for a total of 6 stings). Two patients (3 stings), with a previous clinical history of a grade III and IV reaction, did not experience any reaction. One patient, with a previous grade II reaction, showed a large local reaction. The fourth patient, with a previous grade III reaction, was re-stung twice (after 12 and 24 months) with two systemic reactions (SR) (mild throat constriction). During the ultrarush SCIT phase, 3 (15%) patients experienced side-effects: 2 of them showed a large local reaction and 1 had headache and stomach ache. Specific IgE showed a significant (P=0.001) increase after 6 months of treatment and then returned to baseline levels while specific IgG showed a significant (P=0.001) increase after 6, 12 and 24 months in comparison with baseline. Nine patients were field-stung during the treatment: 8 of them experienced large local reactions; one patient (11%) experienced an SR (dizziness). Our results, even if in a small number of patients, suggest that in patients with Hymenoptera sting allergy SLIT could be efficacious with a good tolerability profile when compared to SCIT. Larger studies are needed to assess efficacy, safety and tolerability profile of wasp venom SLIT.

Sepsis is a clinical syndrome characterized by non-specific inflammatory response with evidence of profound changes in the function and structure of endothelium. Recent evidence suggests that vascular maintenance, repair and angiogenesis are in part mediated by recruitment from bone marrow (BM) of endothelial progenitor cells (EPCs). In this study we were interested in whether EPCs are increasingly mobilized during sepsis and if this mobilization is associated with sepsis severity. Our flow cytometry data demonstrate that in the CD34+ cell gate the number of EPCs in the blood of patients with sepsis had a four-fold increase (45 ± 4.5% p<0.001) compared to healthy controls (12 ± 3.6%) and that this increase was already evident at 6 hours from diagnosis (40.6 ± 4.2%), reaching its maximum at 72 hours. Also the percentage of cEPCs identified in the patients with sepsis (35 ± 4.6% of the CD34+ cell) was statistically different (p<0.001) compared to that found in the blood of patients with severe sepsis (75 ± 4.9%). In addition, we proved that at six hours after sepsis diagnosis, VEGF, CXCL8 and CXCL12 serum levels were significantly higher in septic patients compared to healthy volunteers 559 ± 82.14 pg/ml vs 2.9 ± 0.6 (p<0.0001), 189.8 ± 67.3 pg/ml 15 vs 11.9 ± 1.6 (p=0.014) and 780.5 ± 106.5 pg/ml; vs 190.2 ± 71.4 (p < 0.001). Our data suggest that the cEPC evaluation in peripheral blood, even at early times of diagnosis, in patients with sepsis can be envisaged as a valuable parameter to confirm diagnosis and suggest further prognosis.

Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, only in a few groups of penicillin-allergic patients. The aim of this study is to evaluate the tolerability of aztreonam in a large group of betalactam-allergic patients. We studied all patients (> 14 years of age), with a clinical history of immediate reactions to any betalactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied betalactam; they were studied by means of: skin prick and intradermal tests with penicilloyl polysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. Patients with negative immediate-type skin tests with aztreonam then underwent a graded intramuscular challenge. Forty-five patients (mean age 46.1 ± 15.2 years), 27 females and 18 males, had positive skin tests and/or specific IgE to at least one of the studied betalactams. The most involved drugs were amoxicillin (23 cases), ampicillin (9 cases), penicillin G (8 cases) and other betalactams in the remaining cases. The most frequent reactions were anaphylaxis (27 cases) and urticaria (15 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Our data confirm the lack of cross-reactivity between betalactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in betalactam-allergic patients who urgently need this drug.

Aminopenicillins are the most used ß-lactam antibiotics. Morbilliform or maculopapular rashes are rather frequent during therapy with aminopenicillins. The pathogenesis of these reactions is often due to a cell-mediated allergy. The aim of this work is to characterize patients with cell-mediated allergy to aminopenicillins and to identify alternative ß-lactam drugs that can be safely administered to these patients. We studied 27 subjects affected by cell-mediated allergy to aminopenicillins. The diagnosis was made on the basis of positivity of patch tests with aminopenicillins. These patients then underwent an allergological evaluation (skin and patch tests, oral and/or intramuscular challenge tests) with a wide spectrum of ß-lactam antibiotics. Our work highlights the following main characteristics of cell-mediated allergy to aminopenicillins: time elapsing between drug administration and onset of symptoms of about 2 days; the maculopapular rash and delayed appearance of urticaria/angioedema were the most typical symptoms (82.8% of cases); a cross-reactivity with aminocephalosporins is usually absent, or it is limited to cephalexin (in our study, in fact, just 3 out of 20 patients challenged with cephalexin showed a positive oral challenge test); all the ß-lactams, other than aminopenicillins, are well tolerated. Patch tests represent a specific diagnostic tool with a good predictive value of identifying alternative drugs that can be safely administered to patients with ß-lactam allergy. Our patients could tolerate other ß-lactam drugs after a complete allergological evaluation. On the basis of our study, cell-mediated allergy to aminopenicillins should be considered a well-defined nosologic entity.

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).

In the literature there are several reports dealing with the possibility of a desensitising treatment in food allergy, but there are very few studies concerning the immunological mechanisms of or al desensitisation. We studied the immunological modifications in four children who underwent oral desensitisation with cow milk. Four children with cow milk allergy underwent oral desensitisation according to a standardized protocol. Total IgE, eosinophilic cationic protein in serum, and specific IgE and IgG4to α-lactalbumin, to β-lactoglobulin and to casein were determined at the beginning of the treatment and after 6, 12 and 18 months in the 4 children treated. All the 4 treated patients successfully completed the treatment. Specific IgE to casein showed a significant reduction (p<0.01), while specific IgG4to α-lactalbumin (p<0.02), to β-lactoglobulin (p<0.01) and to casein (p<0.01) showed a significant increase. Total IgE, eosinophilic cationic protein, and specific IgE to a-lactalbumin and to β-Iactoglobulin did not show any significant modification. Control patients did not show any immunological modification and still had a positive double-blind, placebo-controlled food challenge.These results make us think that oral desensitisation in food allergy occurs with the same mechanisms of traditional desensitising treatments for respiratory and insect sting allergies.

Multiple Chemical Sensitivity (MS) is characterized by a wide range of symptoms when affected patients come into contact with several chemical products. Very little is known of either the diagnosis or the suitable treatment. In this study we report the case of a 38-year-old woman, previously diagnosed as suffering from MCS, who was referred for an oral health evaluation. After removing all the existing restorations and extracting the diseased teeth, a removable partial denture without metal structure was made after testing her hypersensitivity to these materials. The one year follow-up of the patient did not show any remarkable reaction, confirming the reduction of a large number of MCS symptoms and the increase in her quality of life.

Nickel (Ni), the main responsible for allergic contact dermatitis worldwide, is also involved in systemic condition called “Systemic Nickel Sulfate Allergy Syndrome (SNAS).” Likewise, IgE-mediated reactivity to Lipid Transfer Protein (LTP) represents the main cause of primary food allergy in adults of Mediterranean countries. We evaluated the prevalence of SNAS in LTP allergic patients and investigated patients’ clinical features with double sensitization (LTP and Ni). A retrospective, single-center, observational study was conducted performing a complete allergological work-up including: (1) skin prick tests; (2) serum specific IgE for plant food allergens and rPru p3 (LTP); (3) patch test with 5% Ni sulfate in petrolatum. We enrolled 140 LTP allergic patients of which 36 patients (25.7% of sample) showed additional positivity to Ni patch test. Patients with double sensitization were more frequently females and reported fewer cutaneous symptoms. Higher values of sIgE for peach, apple, peanut, walnut, grain, corn, and garlic were found in LTP allergic patients, while higher values for hazelnut in the other subgroup. The prevalence of SNAS in the LTP allergic population is clinically relevant. Moreover, the clinical and immunological profiles of patients with double sensitization were different from patients monosensitized to LTP.

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< 0.01 for all indices, except depressed mood). Finally, 33 patients performed the MMPI-2. High rates for hypochondriasis and depression were noted. Furthermore, most of the patients had high scores for anxiety, depression, and health concerns. This is the first study showing that NiOHT improves HRQoL of SNAS patients, which can be considered a “personalized medicine” approach.

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.

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.