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Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine-acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine-acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence.

Asthma is a heterogeneous disease usually characterized by chronic airway inflammation and recognized as the most prevalent chronic illness among children. Despite this, the knowledge as to how asthma affects adolescents is still scarce. One of the main management problems of asthmatic adolescents is the poor adherence to pharmacological and non-pharmacological treatments. The assessment of respiratory function and the impact on quality of life are still two crucial challenges in the management of asthmatic adolescents. Additionally, the COVID-19 pandemic has prompted physicians to explore complementary management strategies including telemedicine technologies. This review aims to provide an update on the contribution of respiratory functional tests, how asthma affects quality of life of adolescents and, finally, how telemedicine contributes to the management of adolescent asthmatics during the COVID-19 pandemic

A low-nickel (Ni) diet, a key treatment for Systemic Nickel Allergy Syndrome (SNAS), is difficult in the long term and strongly impacts quality of life (QoL). Hydroponic agriculture could be an alternative to allow the reintroduction of tomato, an essential food in the global diet. In a first interventional, randomized, double-blind, single-center crossover study, we compared the possible effects of eating tomato puree deriving from hydroponic agriculture versus tomato puree from conventional cultivation, collecting data on subjective control of SNAS symptoms, adherence to treatment, and impact on QoL. Thirty subjects were randomly assigned to one of the following treatment groups: (1) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from hydroponic technology; (2) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from conventional cultivation. Then, after a 2-week washout period on the low-Ni diet, each patient crossed over to the other treatment. Patients reported lower symptom scores after eating Datterino tomato puree deriving from hydroponic technology; specifically, bloating (p = 0.0111, p = 0.0060), flatulence (p = 0.0090), abdominal cramps (p = 0.0207), constipation (p = 0.0395), and diarrhea (p = 0.0105). Overall, the adherence rate was high for both treatment arms. At baseline, QoL was poor, but significant improvement was observed after two treatments. In our study, precision medicine and precision agriculture merge in a holistic approach to the challenges of food allergies.

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly.Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods.Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro.Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p < 0.001), also using fresh cooked or raw food (p < 0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to tolerant subjects, but 33% of patients were not detected by any of the available molecules. Overall, a higher frequency of IgE rectivity to shrimp was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south.Conclusion: The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detecti

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 Peanut allergy has not been well characterized in Italy. Objective Our aim was to better define the clinical features of peanut allergy in Italy and to detect the peanut proteins involved in allergic reactions. Methods A total of 22 centers participated in a prospective survey of peanut allergy over a 6-month period. Clinical histories were confirmed by in vivo and/or in vitro diagnostic means in all cases. Potential risk factors for peanut allergy occurrence were considered. Levels of IgE to Arachis hypogea (Ara h) 1, 2, 3, 6, 8, and 9 and profilin were measured. Results A total of 395 patients (aged 2-80 years) were enrolled. Of the participants, 35% reported local reactions, 38.2% reported systemic reactions, and 26.6% experienced anaphylaxis. The sensitization profile was dominated by Ara h 9 (77% of patients were sensitized to it), whereas 35% were sensitized to pathogenesis-related protein 10 (PR-10) and 26% were sensitized to seed storage proteins (SSPs). Sensitization to 2S albumins (Ara h 2 and Ara h 6) or lipid transfer protein (LTP) was associated with the occurrence of more severe symptoms, whereas profilin and PR-10 sensitization were associated with milder symptoms. Cosensitization to profilin reduced the risk of severe reactions in both Ara h 2– and LTP-sensitized patients. SSP sensitization prevailed in younger patients whereas LTP prevailed in older patients (P < .01). SSP sensitization occurred mainly in northern Italy, whereas LTP sensitization prevailed in Italy's center and south. Atopic dermatitis, frequency of peanut ingestion, peanut consumption by other family members, or use of peanut butter did not seem to be risk factors for peanut allergy onset. Conclusions In Italy, peanut allergy is rare and dominated by LTP in the country's center and south and by SSP in the north. These 2 sensitizations seem mutually exclusive. The picture differs from that in Anglo-Saxon countries.

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.

Background: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. Methods: Thirty-one patients (age 18-64 years) receive intranasal (mometasone furoate, 200 mu g b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin' sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. Results: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. Conclusions: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR.

Hypersensitivity reactions (HRs) to contrast media (CM) are a major problem. We compared differences of HRs to iodinated contrast media (ICM) versus gadolinium-based contrast media (GBCM), collecting data on prevalence, type, latency and severity. Secondly, the predisposition to perform new contrast tests, use of premedication and possible appearance of new reactions were explored in a long-term follow-up of 5 years. Clinical data, comorbidities, skin test (ST) results, re-exposure to CM procedures with any new reactions, premedication and CM used were collected. In a retrospective single-center study, 350 patients with mild to moderate HRs were enrolled. Asthma, food allergy, non-allergic drug hypersensitivity and neurologic disease were significantly more frequent in patients with HRs to GBCM compared to the high evidence of cardiovascular disease and history of cancer in patients with HRs to ICM. A marked delay in performing STs was reported by patients with negative results (66 months, p < 0.01). Iomeprol, iopamidol and gadobenic acid were the culprit CM most involved in HRs in patients with positive STs. During follow-up, 7.1% of responders reported new HRs to CM despite negative STs, premedication and infusion of alternative CM in most cases

Non-cystic fibrosis bronchiectasis is a chronic disorder in which immune system dysregulation and impaired airway clearance cause mucus accumulation and consequent increased susceptibility to lung infections. The presence of pathogens in the lower respiratory tract causes a vicious circle resulting in impaired mucociliary function, bronchial inflammation, and progressive lung injury. In current guidelines, antibiotic therapy has a key role in bronchiectasis management to treat acute exacerbations and chronic infection and to eradicate bacterial colonization. Contrastingly, antimicrobial resistance, with the risk of multidrug-resistant pathogen development, causes nowadays great concern. The aim of this literature review was to assess the role of antibiotic therapy in bronchiectasis patient management and possible concerns regarding antimicrobial resistance based on current evidence. The authors of this review stress the need to expand research regarding bronchiectasis with the aim to assess measures to reduce the rate of antimicrobial resistance worldwide.

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Background: Restrictions due to the COVID-19 pandemic limited patients’ access to hospital care. The aims of this study were to assess dietary nutritional status, quality of life (QoL), and adherence to dietary therapy before and after 30-day personalized diet therapy through telenutrition tools in patients with systemic nickel allergic syndrome (SNAS). Methods: Each SNAS patient underwent the following allergological procedures: (a) face-to-face visit (nutritional visit and QoL evaluation) with prescription of one out of five personalized and balanced dietary plans different for calorie intake, (b) video call visit for dietary evaluation and assessment of adherence to diet after 15 days, and (c) video call visit for dietary and QoL evaluation and assessment of adherence to diet therapy after 30 days (end of study). Results: We enrolled 20 SNAS patients. After 15 and 30 days, we found a statistically significant improvement in anthropometric findings after diet therapy, a significant adherence rate to low-nickel diet (60% and 80%, respectively), and an improvement in QoL with an increase in almost all psychometric indices. Conclusions: Our study demonstrates that telenutrition can be a valid tool to monitor nutritional status and adherence to balanced low-Ni diet positively affecting QoL in SNAS patients during the COVID-19 pandemic.

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 o

BACKGROUND: Chlorhexidine is a synthetic biguanide with a broad antibacterial activity and has become an important cause of perioperative anaphylaxis.OBJECTIVE: Reactions due to chlorhexidine allergy are usually IgE-mediated. The aim of this report is to demonstrate utility of laboratory in-vitro testing for diagnosis.METHODS: We report the case of a 36-year old man who experienced severe anaphylaxis during general anesthesia. He underwent skin tests, specific detection of specific IgE to chlorhexidine and basophil activation test (BAT).RESULTS: Skin tests gave false positive results due to dermographism. So, on the basis of a clinical reaction to chlorhexidine and positive tests for IgE to chlorexidine and BAT, we assessed the diagnosis of chlorhexidine allergy.CONCLUSIONS: Physicians should be aware of the role of chlorhexidine in the etiology of perioperative anaphylaxis. In vitro testing such specific IgE and BAT are useful in patient with suspected chlorexidine allergy and limitation to perform skin tests.

BACKGROUND: Thiocolchicoside is a muscle relaxant, anti-inflammatory, and analgesic. Administered orally, intramuscularly, or topically, this drug is used in the symptomatic treatment of muscular spasms and rheumatologic disorders. Despite its extensive use, thiocolchicoside is a very rare sensitizer.OBJECTIVE: To evaluate IgE-mediated reaction to thiocolchicoside by basophil activation test.METHODS: Allergological work-up with skin prick tests, intradermal tests and basophil activation test with thiocolchicoside.RESULTS: We report the first case of immediate reaction to thiocolchicoside confirmed by basophil activation test in addition to positive skin tests.CONCLUSIONS: BAT can be considered a complementary diagnostic tool to demonstrate an IgE-mediated reaction also for muscle relaxant drugs.

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.

Background and aims: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Background: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. Objective: To detect the risk factors for systemic reactions induced by labile food allergens. Methods: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. Results: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P <.025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P <.025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. Conclusion: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.

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.

Background: Allergic eyelid dermatitis is a common but often misdiagnosed disease that is related to eyedrops, topical cosmetics or skin care products. With regard to eyedrops, adverse reactions can be caused by both active ingredients and excipients. Identification and elimination of causative agents is the mainstay of management. Patient and Methods: We describe the case of a woman who had been suffering from eyelid and peripalpebral dermatitis for four months. To treat her glaucoma, for a year she used several eyedrops for one year, switched by the ophthalmologist several times. She has also been reported oculorhinitis in March for some years. The patient underwent an allergological work-up consisting in prick test for inhalant allergens and patch tests with the G.I.R.D.C.A. series, benzalkonium chloride 0.1% aq., all the involved eyedrops and additional eyedrops ‘as is’. Results: The patch test for the G.I.R.D.C.A. series and benzalkonium chloride as well as prick tests for the main inhalant allergens were negative. Only patch test performed for eyedrops containing timolol - alone or in association with other active ingredients - gave a positive response. Conclusion: In our patient with eyelid and peripalpebral dermatitis, we have ruled out an allergy to the most common contact and inhalant allergens, while we have identified a cell-mediated hypersensitivity to timolol among the several eyedrop used by the patient.

Allergy to natural rubber latex (NRLA) from Hevea brasiliensis is a relevant public health issue, in particular in healthcare workers and groups at risk. Clinical manifestations of NRLA can range from mild skin disorders to life-threatening systemic reactions. Prevention measures remain the gold-standard treatment for patients suffering from NRLA, but the only etiological therapy able to influence the natural history of NRLA is specific desensitization. This review aims to underline the epidemiological, clinical and diagnostic aspects of NRLA, and carries out a complete and wide-ranging review of the current literature on NRLA management and immunotherapy

Background: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We looked for mono-sensitization to peamaclein among Italian cypress-pollen allergic patients. Material and methods: 835 cypress pollen hypersensitive patients from 28 Italian allergy centers under went thorough interview for food-allergic reactions, and SPT with a commercial peach extracts containing peamaclein. In peach reactors, IgE to rPru p 3 was measured, and those scoring negative were enrolled as potentially mono-sensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated by immunoblot and by an experimental ImmunoCAP with rPru p 7. Results: Peach SPT scored positive in 163 (19.5%) patients but 127 (77,9%) were excluded because Pru p 3 reactors. Twenty-four (14,7%, corresponding to 2.8% of the entire study population) were considered as potentially mono-sensitized to peamaclein. Their distribution did not show any geographic preference. Seventeen/24 (70,8%) had a history of food allergy, in most cases (n=15) to peach. Other offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3/18 putative peamaclein allergic subjects reacted to a band at about 7kDa; 4 other patients reacted at about 50-60 kDa. Ten/18 (56%) scored positive for Pru p 7 on ImmunoCAP. Conclusion: Peamaclein allergy and sensitization prevalence seem rare in Italy. Most patients react to peach, albeit other Rosaceae fruits and several citrus fruits may also act as offending foods. Peach and cypress pollen probably share also cross-reacting allergens other than peamaclein.

Nickel (Ni) oral hyposensitization treatment (NiOHT) is an effective management approach for Ni allergy. No healthrelated 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 ShortForm 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

N/A

The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p 1, Pru p 3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein [LTP] and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit

N/A

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.

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.

Gelatin, a collagen protein obtained from cow and pig bones and fish skin is widely used, by the hydrolysis of collagen, in food preparations (sweets, yoghurt, etc.) and as a stabilizer in the pharmaceutical industry. In particular it could be found as an ingredient of drug capsules, plasma expanders, vaccines and plasma substitutes. Systemic allergic reactions to gelatin-containing vaccines and drugs have been proven by anti-gelatin IgE assay [1–3] and by the Basophil Activation Test (BAT) [4]. Bovine gelatin sensitization is commonly associated with cow milk allergy and beef allergy [5]. We report the case of a 14-year-old patient affected by cow’s milk allergy, who experienced lip paraesthesia, generalized itching and dyspnoea with bronchospasm after the ingestion of lyophilised ebastine; the reaction was handled in the emergency room with intramuscular and aerosolized epinephrine, systemic corticosteroids and antihistamines.

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.

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.

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.

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 The Helicobacter pylori eradication rate with standard triple therapy is very low. H. pylori is known to require the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive at the low pH environment in the stomach. Aim To compare the H. pylori eradication rate of a nickel free-diet associated with standard triple therapy and standard triple therapy alone as the first-line regimen. Methods Fifty-two sex- and age-matched patients at the first diagnosis of H. pylori infection were randomized 1:1 into two different therapeutic schemes: (1) standard LCA (26 patients): lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid for 7 days with a common diet; (2) standard LCA plus a nickel free-diet (NFD-LCA) (26 patients). Patients followed 30 days of a nickel-free diet plus a week of lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid starting from day 15 of the diet. Results All patients completed the study. A significantly higher eradication rate was observed in the NFD-LCA group (22/26) versus LCA group (12/26) (p\0.01). Only a few patients (9 of 52) reported the occurrence of mild therapy-related side effects, without any significant differences between the two groups. Conclusions The addition of a nickel-free diet to standard triple therapy significantly increases the H. pylori eradication rate. The reduction of H. pylori urease activity due to the nickel-free diet could expose the bacterium to gastric acid and increase H. pylori’s susceptibility to amoxicillin. Further studies are necessary to confirm this preliminary result.

BACKGROUND AND OBJECTIVE: 13-Lactams are the most commonly used antibiotics but they can cause hypersensitivity reactions. We sought to estimate cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins. METHODS: We studied 97 patients with a clinical history of nonimmediate reactions to a penicillin and a positive patch test result to at least 1 of the penicillins tested. All patients also underwent patch testing with several cephalosporins. Patients with a negative patch test to a cephalosporin underwent test dosing in order to assess tolerability. RESULTS: We recorded 129 reactions. The most commonly involved drugs were aminopenicillins, and the most widely reported symptoms were delayed urticaria and maculopapular exanthema. Seventeen patients had positive patch test results for cephalosporins, mostly for cephalexin (n=10), cefaclor (n=9), and cefuroxime axetil (n=5). All the patients-except 4 who experienced an exanthema after the challenge test with cephalexin-tolerated a therapeutic dose of the cephalosporin tested without any adverse effects. CONCLUSIONS: Our data show that cross-reactivity between penicillins and cephalosporins may be as high as 10.9% for first-generation cephalosporins and 1.1% for third-generation cephalosporins, possibly due to the involvement of similar side chains. Patch tests are a useful diagnostic tool to assess cross-reactivity, but a graded challenge is mandatory because a negative patch test does not always mean tolerability.

The Helicobacter pylori eradication rate with standard triple therapy is very low. H. pylori is known to require the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive at the low pH environment in the stomach.

The prevalence of individuals allergic to latex, exhibiting cross-hypersensitivity with plant-derived food has been frequently reported as the so-called latex-fruit syndrome. Nonetheless, molecular mechanisms underlying allergy to latex and/or fruit are poorly understood.The aims of this study were to identify candidate genes that may be associated with the pathogenesis of allergy to latex and/or vegetable food, and to assess if similar molecular pathways are involved in both types of hypersensitivity. MATERIALS AND METHODS: DNA microarray analysis was performed to screen the molecular profiles of peripheral blood mononuclear cells isolated from patients with allergy to latex, to fruit, or with latex-fruit syndrome, and from control healthy subjects. RESULTS: Molecular profiling identified an overlapping dataset of genes commonly regulated in all the atopic patients enrolled in this study, suggesting that similar molecular mechanisms are involved in the pathogenesis of allergy to the fruit and/or latex. Several regulators of the innate and acquired immunity reported to polarize the immunological response towards a Th2-mediated immune response were overexpressed in the patients. Evidences suggested that the expression of T-regulatory cells might be defective in allergic patients, as a consequence of a dysregulation of some inflammatory cytokines. Finally, several transcription factors that may be responsible for the Th1/Th2 imbalance were modulated in allergic patients. CONCLUSIONS: This study identified relevant genes that may help to elucidate the molecular mechanisms underlying allergic disease. Knowledges of critical targets, along with transcription factors regulating gene activity may facilitate the development of new therapeutic options

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.

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

Profilin desensitization in two patients with plant-derived food allergy

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.

We present the case of a woman with 'empty sella syndrome' who experienced generalized urticaria after the administration of sodium succinate hydrocortisone in two episodes.

A case of IgE-mediated allergy and cell-mediated allergy to Seaprose-S in the same patient.

Delayed hypersensitivity to heparin in a patient with cancer: fondaparinux may be safe but needs to be tested