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Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Background: This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with “systemic nickel allergy syndrome” (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. Methods: Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5th month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. Results: During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). Patients reported no side-effects. Conclusions: NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.

Aims The study aimed to evaluate the effects of probiotic Lactobacillus reuteri DSM 17938 strain supplementation in patients suffering from systemic nickel allergy syndrome, in terms of modulation of faecal LAB population linked to a reduction of GI and cutaneous symptoms and to an increase of patient's quality of life. Methods and Results A preliminary double-blind randomized placebo-controlled study was planned and a culture-independent method based on denaturing gradient gel electrophoresis (DGGE) analysis coupled to the 16S rRNA gene sequencing was applied to investigate on the dynamics of faecal LAB communities before and during a low-Ni diet, supplemented with the probiotic strain. Moreover, the severity and the frequency of GI and cutaneous reactions as well as patient's clinical condition perception (VAS scores) were estimated by statistical analysis. PCR-DGGE fingerprinting obtained using LAB-specific primers revealed significant shift in faecal community with an increase in biodiversity in patients supplemented with probiotic Lact. reuteri strain. In addition, GI reactions such as symptoms related to meals and type of stools significantly improved only in patients treated with Lact. reuteri, while severity and frequency of cutaneous symptoms (urticaria, itch and eczema) and recurrent abdominal pain (RAP) as well as VAS scores statistically decreased in both groups. Conclusions Our preliminary findings suggest that probiotic Lact. reuteri could be a useful supplementation during a low-Ni diet of patients with SNAS, to increase LAB population diversity, which could contribute to restore the intestinal homoeostasis conditions. Significance and Impact of the Study To date, no information is available on probiotics application and on their effects, in terms of intestinal microbiota modulation, on patients suffering from SNAS. Therefore, the identification of dominant LAB community and the study of its shift during the probiotic supplementation could enhance the knowledge of the SNAS syndrome.

The prevalence of nickel hyper-sensitivity varies widely in different countries, nevertheless it is the leading cause of contact dermatitis. The presence of nickel in the diet (mainly plant foods) in some nickel-sensitive subjects can provoke/aggravate eczema and systemic contact dermatitis as well as cause extra-cutaneous symptoms (respiratory, gastrointestinal, neurological). These symptoms, correlated to the ingestion of nickel-containing foods and beverages, in nickel patch test positive individuals, defines the so called Systemic Nickel Allergy Syndrome (SNAS), a condition successfully treated by oral desensitization. Although numerous studies have investigated the prevalence of contact nickel allergy or addressed the relationship between nickel intake and onset of systemic symptoms, to our knowledge no epidemiological studies have attempted to estimate the prevalence of SNAS. Therefore, we decided to evaluate consecutive patients (1,696), afferent to four allergy units in Sicily, a region of southern Italy, from October 2010 to March 2011. SNAS was confirmed in 98 patients (5.78 percent) of the 1,696 studied, suggesting that this clinical entity may be an emergent allergological condition rather than an occasional finding. The most common symptoms complained of in our population were cutaneous (51 patients), gastrointestinal (87 patients) and other systemic clinical manifestations (37 patients). Furthermore, 16 out of the 98 SNAS patients (16.3 percent) presented IgE-mediated food allergy with a statistically significant association (X2=16.950; P

Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid administered in accordance with the standard regimen has proven to be effective and safe. Achieving clinical benefit, however, requires a lengthy period of time so it is not very suitable for short-lasting allergies. We thus performed this study to compare an administration protocol starting in the coseasonal period (with a 4-day build-up phase) with a precoseasonal scheme to verify if the former regimen provides the same benefit in a shorter period of time. The prospective, randomized, drug therapy-controlled study was conducted in 33 rhinitic patients monosensitized to Olea with or without asthma. Ten patients were assigned to the coseasonal therapy with 5000 allergic units (AU)/week for 6 weeks, 11 to the precoseasonal therapy with 3000 AU/week for 10 weeks, and 12 to drug therapy. They were treated from April or May to June 2008. A visual analog scale (VAS) was performed at baseline and after treatment to assess the well being of the patients. Drug consumption was evaluated by means of a monthly diary. There was greater VAS improvement in both the SLIT groups versus the controls, but it was statistically significant only in the coseasonal group (p < 0.01). Furthermore, there was a reduction in the rescue medication only in the coseasonal SLIT (p < 0.05 versus drug therapy). One mild adverse event was observed. The allergoid SLIT was shown to be effective and safe in Olea allergy in particular when a coseasonal regimen was used.

Nickel sensitization can not only induce allergic contact dermatitis (ACD), but also can induce an overlapping disease referred to as "systemic nickel allergy syndrome" (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. This study was designed to determine if oxidative stress occurs in patients with nickel allergy. Thirty-one female patients (mean age 31.26 + 13.04 years, range 16-64 years) with confirmed nickel CD underwent oral nickel challenge because of clinically suspected SNAS; serum concentrations of protein carbonyl groups (PCGs) and nitrosylated proteins (NPs; biomarkers of oxidative stress) were measured before and after oral nickel challenge as well as in healthy female controls. Twenty-three of these 31 patients were diagnosed with SNAS because they had a positive reaction to the oral nickel challenge, and 8 patients had no reaction and therefore were classified as patients with contact nickel allergy only. Although both nickel-allergic patients and controls presented similar serum levels of PCGs, NP values in nickel-allergic patients appeared higher than in controls and tended to decrease after the challenge; furthermore, serum levels of NPs in patients affected by SNAS were higher (although not significantly) than in patients with nickel ACD only. The involvement of specific biomarkers of oxidative stress such as NPs and the lack of involvement of other biomarkers such as PCGs may help to better understand the alteration of the redox homeostasis occurring in nickel ACD and particularly in SNAS.

A 34-year-old woman referred episodes of gastrointestinal disorders and sometimes angioedema of the lips which appeared within 2 hours from the ingestion of packed food like biscuits, cereals or fruit juice. A patch test with the standard European series and with food preservatives was positive for fragrances mix. The avoidance of packed food labelled as containing flavours among the ingredients caused the disappearance of the above reported symptoms.

Since the first case reported in 1927, latex allergy has attracted the attention of allergists including its capacity to cross-react with fruits. To evaluate the frequency of sensitivity to some fruit allergens shown to cross-react with latex, we evaluated 82 patients (43 men and 39 women, aged between 18 and 45 years) with latex allergy. All patients underwent skin tests with various fruit extracts that potentially cross-react with latex. Only patients with negative prick tests successively underwent prick-by-prick tests with fresh fruits. Thirty-nine of 82 patients (47.5%) were found to have positive skin tests. Prick tests with fruit extracts were positive in 28 patients (kiwi, 21 patients; banana, 17 patients; avocado, 8 patients; and papaya, 3 patients), and the prick-by-prick test had positive results in 11 patients (kiwi, 7 patients; banana, 4 patients; and avocado, 3 patients). In our experience patients with latex allergy are at a high risk of sensitization to some fruits and they often develop allergic reactions, even severe ones, after eating them; for this reason fruit sensitization should be taken into consideration when investigating patients allergic to natural rubber latex.

(2003). Adverse Reactions to Pantoprazole. Scandinavian Journal of Gastroenterology: Vol. 38, No. 7, pp. 800-800.

Summary We present the case of bronchospastic reaction to clarithromycin had during a drug challenge test Personal allergic history was negative for respiratory allergies and positive for adverse drug reactions to general and regional anesthesia and to ceftriaxone After the administration of 1/4 of therapeutic dose of clarithromycin the patient showed dyspnea, cough and bronchospasm in all the lung fields The positivity of the test was confirmed by the negativity to the administration of placebo The quickness and the clinical characteristic of the adverse reaction suggest a pathogenic mechanism of immediate-type hypersensitivity On reviewing the literature we have found no reports of bronchospastic reaction to clarithromycin Macrolides are a class of antibiotics mainly used in the last years in place of b-lactams because of a broad spectrum of action and a low allergic power. In fact, there are few reports on allergic reactions to these molecules Clarithromycin is one of the latest macrolides, characterised by the presence of a 14-carbon-atom lactone ring as erythromycin, active on a wide spectrum of pathogens

Nickel can elicit both Th1-type andTh2-type responses in vitro (1) inpatients with nickel allergic contactdermatitis,butthiscomplexcytokinecascade has still to be clarified. Therecently discovered Th17 subset,which has crucial functions in hostdefence against infections and hasbeen implicated in the developmentofautoimmunediseases(2),hasbeensupposed to play an important rolein some inflammatory and autoim-mune skin disorders, such as contacthypersensitivity(3)andpsoriasis(4),respectively. Th17 cells are charac-terized by expression of interleukin(IL)-6, tumour necrosis factor-a,granulocyte–macrophage colony-stimulating factor, IL-17A, IL-17F,IL-21, IL-22, and IL-26 (5).Among these cytokines, IL-22,a member of the IL-10 cytokine fam-ily, described as having proinflam-matory activities on liver, pancreas,intestine, and skin (reviewed in 6),has been demonstrated to have a cru-cial function in the development ofdermal inflammation and epidermalacanthosis induced by IL-23 in mice(4). Moreover, IL-22 seems to beinvolved in the pathogenesis of psori-asis in humans, as demonstrated bythehighserumlevelsshowedbypsori-atic patients and the high levels pro-duced by T cells isolated by psoriaticskin (6), where the IL-22 receptor isexpressed on a variety of epithelialtissues(4).However,nodataareavail-ableon thepossibleroleplayed byIL-22in nickel contacthypersensitivityinhumans, thus we measured the circu-latinglevelsofthiscytokineinpatientswith allergic nickel contact dermatitis.We enrolled 31 female patientsaffected by allergic contact dermatitisto nickel (mean age 31.9 years; range17–64 years) diagnosed followingpatch testing in accordance withthe International Contact DermatitisResearch Group guidelines. Bloodsamples were collected after patchtesting during a period of clinicalremission 1 month after nickel con-tact avoidance.15 sex- and age-matched blooddonors, with no contact dermatitisand negative patch tests, were re-cruited as controls. Each subject gavepreviously used written, informedconsent to the study.Serum IL-22 was measured usingan enzyme-linked immunosorbentassay kit (R&D System Europe,Abingdon, UK). All samples wereanalysed in duplicate.Differences in IL-22 blood levelswere assessed by the Student’s t-testfor unpaired comparison, assumingunequal variances. Data were ex-pressed as mean standard devia-tion. A P value

Background: New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy. We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica-induced respiratory allergy. Methods: A double-blind, placebo-controlled design was followed. Thirty patients with P. judaica rhinoconjunctivitis, mild asthma, or both were randomly chosen for sublingual immuno-therapy (14 patients) or placebo treatment (16 patients). The patients underwent preseasonal rush induction treatment followed by coseasonal maintenance treatment during the Parietaria pollen season. Symptom and drug scores, as well as specific IgE and specific IgG4, were recorded. Results: Significantly lower symptom and drug scores were found (P=0.04), especially during the Parietaria pollination period, in the immunotherapy group. No significant difference in specific IgE and specific IgG4 was detected between the active and placebo groups; a statistically significant increase of specific IgE was detected in both groups (P=0.05). No patient undergoing active sublingual immunotherapy reported local or systemic side-effects. Conclusions: Our data suggest that sublingual immunotherapy is both clinically effective and safe in treating patients with Parietaria-induced rhinoconjunctivitis and mild asthma.

Among the most frequently used drugs in the treatment of allergic rhinitis we have to mention topical nasal corticosteroids and H1 antihistamines used both systemically and topically. The present study focused the effectiveness and tolerability of cetirizine and fluticasone propionate in seasonal allergic rhinitis. 54 patients, divided into three homogeneous groups, underwent the following different treatments: Group 1: Placebo of fluticasone (2 puff per nostril once daily by aerosol) + cetirizine (10 mg/die per os) for 60 days. Group 2: Fluticasone (100 mg per nostril once daily by aerosol) + placebo of cetirizine (per os) for 60 days. Group 3: Cetirizine (10 mg/die per os) for 60 days + fluticasone (100 mg per nostril once daily by aerosol) for 20 days. The patients reported nasal symptoms (sneezing, obstruction, itching, rhinorrea) on a clinical diary. ECP levels in nasal secretions were investigated in all patients to determine the anti-inflammatory activity of both treatments. Cetirizine resulted very effective in the treatment of sneezing, itching and acqueous rhinorrea whereas not much effective on nasal obstruction. On the contrary, fluticasone, which acted effectively on nasal obstruction, resulted inefficacious on the other symptoms. The third group of patients achieved the best results on all four symptoms, including obstruction, which continued even after interrupting the treatment with fluticasone. The ECP levels were significantly reduced by both treatments. The side effects in all 3 groups were rare and not serious. From these results we can assert that the synergic action of the two drugs, achieves the best effectiveness, that the fluticasone treatment can be limited to 20 days cycles and finally that both molecules are well tolerated.

In order to evaluate the efficacy and tolerability of lodoxamide in the treatment of allergic conjunctivitis, the authors conducted a double-blind trial with intrapatient comparison on 32 patients, using lodoxamide versus spaglumic acid in the course of two conjunctival provocation tests performed with specific allergens. The patients received one drop of lodoxamide in one eye and one drop of spaglumic acid in the other; 15 minutes later, 25 microliters of allergen extract at a pre-established concentration was instilled. After 10 minutes, the signs and symptoms of the allergic response were evaluated and recorded. Six hours later, the instillation of the allergen extract in both eyes was repeated following the same procedure, to establish the duration of the effect of the two drugs. The results, obtained by evaluating the main clinical signs and symptoms (itching, lacrimation, hyperaemia, palpebral oedema and chemosis), demonstrate with statistically significant differences that lodoxamide inhibits the conjunctival response to exposure to the allergen with greater efficacy than spaglumic acid, and for a longer duration. The two drugs provided similar and satisfactory tolerability. In view of these results, lodoxamide can definitely be considered and effective drug in the treatment of allergic conjunctivitis.

Design of study Two groups of patients undergoing long-term dialysis were studied in order to evaluate the importance of ethylene oxide (EtO) in causing allergic reactions during dialysis. The first group of 50 subjects had never shown any hypersensitivity reactions related to dialysis, whereas the second group of 20 subjects had previously complained of reactions. All the patients underwent a prick test with a standard kit of aeroallergens in order to assess the presence of atopy (in doubtful cases a RAST test was carried out with the same aeroallergens). A blood sample for the investigation of EtO specific IgE antibodies was taken from all the patients; the immunoenzymatic method was used. Results Sensitivity to EtO is significantly higher in the group of patients with previous allergic reactions during dialysis (55 vs 6% in the control group).

Although copper sulfate can cause systemic contact dermatitis, few such cases have been recorded among copper-releasing IUD users. Reported in this paper is a case of endometritis and urticaria-angioedema syndrome in a 32-year-old user of a copper IUD. Widespread urticaria, as well as angioedema of the eyelids and the labia majora and minora, persisted for about 6 months and were not responsive to corticosteroids and H1-antagonists. Copper sulfate positivity was demonstrated in 72-hour patch test, 48-hour application of the copper spiral to forearm, and in vitro lymphocyte-stimulating test. Histologic examination of the endometrial biopsy revealed vulvovaginitis with hyperplasia of the cervical canal and T-cell and eosinophilic granulocyte infiltration. Removal of the IUD caused complete symptom remission. In experimental animals with a radioactively labeled copper IUD, small amounts of copper sulfate are absorbed through the mucus membrane and carried to the cutis through the blood or lymph. In the cutis, the allergen is intercepted from antigen-presenting cells and recognized by T cells that migrate to the lymph nodes with blastic transformation, proliferation of cytotoxic lymphocytes, and cytokine production.

School and Division of Allergy and ClinicalImmunology, University of Messina, Messina, ItalyKey words: nickel; endogenous dermatitis; IL-12;IL-10.Dr Luisa RicciardiScuola di Specializzazione in Allergologia eImmunologia Clinica PoliclinicoPadiglione H98100 MessinaItalyTel: +39 090 2212080Fax: +39 090 694773

Background Anisakis simplex , a fish and cephalopodes parasite, can cause either gastrointestinal symptoms or allergic reactions in humans on eating/handling contaminated fish. Objective The aim of our study was to determine the capacity of Anisakis simplex to induce specific IgE production and allergic reactions following eating and handling fish in a population at risk. Methods We determined the levels of total IgE, specific IgE, and eosinophil count in 28 fishermen/fishmongers (group A) and 15 healthy donors (group B). A skin prick test (SPT) with extracts from Anisakis and the most common species of fish in our country, were also carried out. Results Specific IgE to Anisakis were found in 14 subjects of group A (13 of them had a positive SPT to the same extract) and none of group B (only one subject had a positive SPT). The SPT with fish extracts was positive in 4 patients of group A but in none of group B. Subjects in group A with specific IgE to Anisakis showed higher total IgE levels and eosinophil counts compared with either other individuals of the same group or to those of group B. Conclusions These results indicate that fishermen/fishmongers are a population at risk for Anisakis simplex sensitization and suggest that this kind of sensitization should also be investigated not only in subjects like fishermen/fishmongers who live in countries where fish is likely to be contaminated with Anisakis simplex parasites, but also in those who handle fish for other reasons.