Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

BACKGROUND: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. OBJECTIVE: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. METHODS: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. RESULTS: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). CONCLUSION: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.

Cross sectional questionnaire-based internet study: Self-perception and clinical course of drug allergy in Greece.

BACKGROUND: Data on self perception of drug allergy in the general population are lacking. Epidemiological studies focus either on specific populations or document adverse drug reactions in general. Our objective was to document self-reported drug allergy in Greece, through a simple, informative internet-based questionnaire. METHODS: A questionnaire on drug allergy was accessible online for a 3-month period. Participants voluntarily answered 28 questions referring to: suspected drug, clinical manifestations, concomitant factors, received treatment, reaction's re-occurrence. RESULTS: A total of 2528 questionnaires were included in study analysis. Beta-lactams and non-steroidal anti-inflammatory drugs were the most prevalent culprit agents (53% and 27.5% respectively) while half of the participants acknowledged skin manifestations as the most common symptoms. One out of three reported subsequent exposure to the drug presumed to be responsible for the reaction and 74.5% of those stated a new reaction upon re-exposure. Only 26.7% underwent allergological evaluation. Reactions manifested with respiratory or cardiovascular symptoms, parenteral administration of the culprit drug and personal history of allergy to agents of >1 different pharmacological categories were associated with increased risk of hospitalization. CONCLUSIONS: Allergic reactions to drugs are adverse events difficult to define and diagnose. A remarkable proportion of presumed as hypersensitivity reactions are not referred to allergists; therefore these patients may be either re-exposed to potentially noxious drugs, or needlessly avoid whole classes of drugs as b-lactams for more costly or less appropriate treatments. Internet-based questionnaires may contribute to awareness programs concerning drug allergy and help improve proper referral.

The role of IL-17, IL-23 and IL-31, IL-33 in allergic skin diseases.

PURPOSE OF REVIEW: Allergic skin diseases such as urticaria, atopic dermatitis and allergic contact dermatitis are among the most common skin diseases with severe socioeconomic consequences. The pathogenesis of allergic skin diseases is complex. This review provides an overview of cytocines IL-17, IL-23, IL-31 and IL-33. RECENT FINDINGS: Current research results show a variety of immunological processes in the pathogenesis of the allergic skin diseases, including the role of cytokines. In addition to the Th1 and Th2 immune response, the immune response via Th17 is becoming increasingly important in allergic skin diseases but also the cytokines IL-23, IL-31 and IL-33 have been discussed in the literature recently. Different cytokines promote in a kind of orchestra the different symptoms seen in the different allergic skin diseases, including pruritus, dermatitis, mast cell mediator release and inflammation. SUMMARY: We are still in the early stages of understanding pathophysiology of allergic skin diseases and the role of various cytokines in the immune system. With the development of targeted antibodies against the proinflammatory cytokines, the variety of normal therapeutic options can be expected to evolve.

Anaphylaxis to gadobenate dimeglumine (Multihance): a case report.

BACKGROUND: Gadolinium chelates are relatively safe contrast media used in MRI. Immediate severe adverse effects are exceptionally rare and mostly concern mild anaphylactoid reactions. We report a case of anaphylaxis to gadobenate dimeglumine (Gd-BOPTA, Multihance), a gadolinium-based contrast agent. METHODS: A 32-year-old female patient with a personal history of multiple sclerosis, while undergoing an MRI scan, developed bronchospasm and acute urticaria with diffuse giant pruritic plaques in the first minute of Gd-BOPTA infusion. The procedure was cancelled and acute treatment of the reaction took place. The patient reported 2 additional MRI scans with definite use of unknown contrast media in the past 2 years without any adverse effect. Blood samples were obtained 2 and 48 h after the reaction for measurement of serum tryptase concentration (Pharmacia Diagnostics, Uppsala, Sweden). Skin prick tests and intradermal tests were performed using 1:1,000, 1:100 and 1:10 dilution of the offending agent and alternative gadolinium-based agents [gadodiamide (Omniscan) and gadoteric acid (Dotarem)]. A group of 10 nonatopic individuals who underwent the same skin testing comprised the control group. RESULTS: Tryptase concentration was highly elevated 2 h after the reaction (21 microg/l) compared with that at 48 h (3 microg/l). Skin prick tests in our patient were all negative, while intradermal testing with 0.03 ml of 1:100 and 1:10 preparations of Multihance showed a definite positive wheal-and-flare reaction. Skin tests to the alternative agents showed no response. In the control group, all performed tests were negative. CONCLUSION: We report the first case of an allergic reaction to gadobenate dimeglumine. Besides, skin testing seems to be a precious diagnostic tool which, if positive, strongly suggests a mast cell-mediated underlying mechanism.

The use of biologicals in cutaneous allergies - present and future.

PURPOSE OF REVIEW: Up-to-date biologicals in cutaneous allergies play - unfortunately - only a minor role. However, this situation might change. Recently, omalizumab was licensed for chronic urticaria; this article reviews recent advances in the use of biologicals in cutaneous allergies. RECENT FINDINGS: Interestingly, the mechanism of omalizumab appears to be different in urticaria and allergic asthma for which the drug has been licensed previously. In urticaria dosage is not dependent on serum IgE-levels and response is seen very often after only 12 h. Other indications in cutaneous allergy in which biologicals have been investigated, at least in case reports or small studies, are TNF-α-antagonists and rituximab in chronic urticaria, omalizumab, rituximab and TNF-α-antagonists in atopic dermatitis as well as mepolizumab in this disease. However, all these studies appear to show a benefit for individual patients but not a clear breakthrough for the whole group of patients involved. This, however, might also be one of the future approaches that sub-groups of patients who have different responses to biologicals may be identified, as apparently different cytokine patterns are predominantly involved in the individual patient. SUMMARY: In conclusion, although currently only one biological is approved in chronic urticaria, there is hope that a rapid better understanding of individual disease factors will support the development of other novel drugs in this field.

Exhaled nitric oxide, bronchial hyperresponsiveness and spirometric parameters in patients with allergic rhinitis during pollen season.

Allergic rhinitis and asthma share common epidemiological features and inflammatory processes. The aim of the present study was to document the influence of natural allergen exposure in exhaled NO (eNO) and in spirometric parameters of patients with seasonal allergic rhinitis(SAR) and to investigate the differences among subjects with positive versus negative bronchial provocation to metacholine(BPMch).Twenty-six non-smoking patients (13F/13M; mean age 28.4ys) with a documented history of SAR, 15 healthy, non-atopic(6F/9M; mean age 37.1ys) and 6 non-symptomatic atopic subjects (3F/3M; mean age 36.5ys) were studied. At the first visit during pollen season each subject filled symptom-score card, underwent eNO and nasal NO (nNO) measurements and spirometry. BPMch was performed within the next 10 days. At the second visit out of pollen season, all measurements but BPMch were repeated. Control subjects underwent eNO and nNO measurements.eNO was significantly increased during pollen season in BPMch positive vs BPMch negative(46.22±32.60 vs 17.81±12.67, p=0.014) and vs non-atopic controls(11.40±5.84, p<0.001) as well as atopic controls(13.56±5.34, p=0.001). No difference was detected out of pollen season in both patients' groups. nNO values were increased only in BPMch(+) group compared to both control groups in pollen season (vs non-atopics p=0.002, vs atopics p=0.002) and only vs non-atopics out of season, p=0.004. Regression analysis has shown that the difference in FEF25-75 values (off season-in season) is a predictor of positive BPMch .eNO is markedly increased in BPMch patients with allergic rhinitis while mid-expiratory flow may represent an early marker of lower airway involvement in respiratory allergy.

Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study.

PURPOSE: To evaluate allergy skin testing as a diagnostic tool of adverse reactions to fluorescein and whether allergy and previous sodium fluorescein angiography (SFA) act as predisposing factors. METHODS: Patients with adequate indication for fluorescein angiography and normal skin responsiveness were subjected to allergy skin-prick and intradermal tests for fluorescein, followed by SFA. During SFA, adverse reactions were monitored and classified as mild, moderate or severe. Previous SFAs and adverse reactions as well as the presence of atopy were also registered. RESULTS: One thousand and thirty-seven patients were enrolled in the study and 1284 SFAs were executed. Forty-four patients (4.3%) developed 55 adverse reactions; among them 50 (3.8%) were mild, three (0.2%) moderate and two (0.16%) severe. None of the reactors produced positive skin tests to fluorescein. Patients with atopy and previous SFAs were not more susceptible to adverse reactions. CONCLUSION: The vast majority of adverse reactions to fluorescein are mild and not attributed to immunological mechanisms. Allergy skin tests cannot predict non-immunological reactions but their utility remains substantial in predicting anaphylaxis during SFAs and must be performed in patients reporting risk factors in their past medical history.

Skin testing and adverse reactions in fluorescein: a prospective study.

Sodium fluorescein (SF) is widely used to assess chorioretinal disorders. Adverse reactions are well documented but the underlying mechanism is still uncertain. The aim of this study was the evaluation of skin testing to predict SF reaction, the identification of possible predisposing factors, and the objective record of the reported reactions. All patients with adequate indication for SF angiography (SFA) during an 18-month period were evaluated as follows: (a) detailed personal history of atopy, diabetes, previous SFA, and/or diagnostic procedures with radiocontrast media (RCM) and possible side effect; (b) skin testing with SF 10% diluted preparations; (c) SFA with 5 mL of SF, objective record of any reaction. Two hundred twenty-four patients (108 men and 116 women) with a mean age of 65.2 years (SD, 12.86; range, 16-92 years) underwent SFA. The overall rate of adverse reactions was 3.6% (8/224), which consists of 5 (2.2%) individuals with transient mild nausea; 2 (0.9%) subjects with face and upper trunk flushing that appeared in one case after 60 minutes and in the other case 24 hours later and both resolved without treatment, and I subject with transient bilateral frontal headache and dizziness. None of the 224 patients had positive skin or intradermal testings. One hundred thirty-six of 224 (60.7%) patients stated no previous SFA and 74.1% had not performed RCM injection. None of the recorded variables correlated with increased risk of reaction. SFA is a safe procedure with minor adverse effects. Although in vivo testing can not identify reactors it may help to exclude an underlying IgE-mediated mechanism in susceptible individuals.

Sensitization to other foods in subjects with reported allergy to grapes.

The grape is widely produced and consumed in the Mediterranean area. The object of this prospective study was to present in detail the clinical features of patients with documented immunoglobulin E (IgE)-mediated reactions to grapes or its products as well as the existing cosensitizations in other food allergens among this population. Sixty-one patients (27 male patients and 34 female patients), aged 14-52 years (mean, 28.8 years) with a documented history of IgE-mediated reactions to grapes or its products (wine, juice, and wine vinegar) were included in this study. In each patient, full allergological data, clinical examination, and specific in vivo (skin-prick tests and prick-to-prick) and in vitro (grape-specific IgE) evaluations were recorded. The diagnostic procedure was extended in other food allergens and molds for exclusion of fruit surface contamination. Thirty-seven of 61 (60.7%) patients had a positive personal history and 24/61 (39.3%) patients had a family history of atopy. Patients reported 3.1 episodes/patient (range, 1-15 episodes) after consumption of grapes or its product. Forty-seven of 61 (77%) patients had presented oral allergy syndrome after eating grapes before the first reported reaction. The mean time for the onset of symptoms was 42 minutes (4-160 minutes). Forty-four of 61 (72.1%) patients reported more than one reaction. The observed prevalence of symptomatology according to the system involved was determined: skin, 57/61(93.4%) patients; respiratory, 46/61(75.4%) patients; cardiovascular, 27/61 (44.3%) patients; and gastrointestinal, 24/61(39.3%) patients. The main cosensitizations were identified (skin-prick tests): apples, 81.9%; peaches, 70.5%; cherries, 47.5%; strawberries, 32.8%; peanuts, 49.2%; walnuts, 42.6%; hazelnuts, 31.1%; almonds, 26.2%; and pistachios, 29.5%. The grape and its products may be the offending agent of IgE-mediated reactions in sensitized individuals. The high prevalence of concomitant reactivity to other fruits elicits the interest of clinical relevance of these findings among the grape-allergic population.

Grape anaphylaxis: a study of 11 adult onset cases.

Reports of immunoglobulin E (IgE)-mediated allergic reactions to grapes and wine are limited in the literature. Nevertheless, grapes are widely grown and consumed in Mediterranean countries. The object of this prospective study was to present clinical features, in vivo and in vitro allergy testing, and human leukocyte antigen (HLA) serotyping in patients with recurring reactions to grapes and grape products. Eleven unrelated Greek patients, six men and five women (aged 16-44 years; mean, 26.9 years) were enrolled based on a documented history of IgE-mediated reactions to grapes, wine, or other grape products. Their evaluation included full history, reaction severity, clinical examination, skin-prick tests with food allergens and molds, serum IgE, specific IgEs to the same allergen battery, and HLA typing. Patients reported 35 grape-induced anaphylaxis episodes ranging from moderate (more than one system involved but not prominent respiratory or cardiovascular symptoms; 45.5%) to severe (serious respiratory obstruction and/or hypotension and loss of consciousness; 54.5%). A causative agent was identified: wine, 10/35 (28.6%); red grapes, 9/35 (25.7%); stuffed vine leaves, 8/35 (22.9%); raisins, 3/35 (8.6%); white grapes, 2/35 (5.7%); wine vinegar, 2/35 (5. 7%); and grape juice, 1/35 (2.9%). Other foods that induced anaphylaxis were apples (54.5%), cherries (18.6%), peaches (18.6%), and bananas (9.3%). Specific IgE values were in accordance with skin-prick tests reactivity. Concerning HLA typing, 9/11 possessed HLA-DR11(5) and -DQ7(3) and the remaining two possessed HLA-DR17(3) and -DQ2 antigens. Grapes, wine and other grape products might cause serious allergic reactions in sensitized individuals. The cosensitization and reaction incidence to other fruit allergens could be a basis for further investigation of panallergens of fruits. HLA class II antigens may contribute in genetic predisposition to these allergic reactions.