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Background: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most prevalent causes of drug hypersensitivity reactions (DHRs), yet the underlying processes are far from clear. Despite the established role of histamine in allergic reactions, its precise implication in DHRs is elusive. Objectives: This study aimed to explore the connection of basal blood histamine levels to the reported NSAID hypersensitivity. Methods: Sixteen patients reporting hypersensitivity reactions to a single or multiple NSAIDs and/or paracetamol and 18 healthy volunteers serving as the normal control group enrolled in the study. The medical history was recorded and histamine was quantified spectrophotofluorometrically in whole peripheral blood and plasma. Results: Compared to the normal group, plasma but not whole blood histamine levels were significantly higher in patients (p < 0.001), mainly in the subgroup reporting hypersensitivity to a single agent (p < 0.001). Plasma histamine levels were significantly correlated with the culprit drug selectivity for cyclooxygenase (COX) isozymes (p < 0.001), with higher levels being obtained in patients reporting reactions to COX-1 than to COX-2 selective inhibitors (p < 0.05). Conclusions: The findings provide first evidence connecting basal blood histamine levels to the reported NSAID-triggered DHRs. Prospective studies are expected to decipher the contribution of histamine-associated parameters to the mechanisms underlying DHRs.

Η συχνότητα των αλλεργικών αντιδράσεων από νυγμούς μέλισσας στουςμελισσοκόμους ποικίλει σημαντικά από χώρα σε χώρα, ενώ δεν υπάρχουν δεδομέναπου αφορούν ειδικά στον Ελλαδικό χώρο.Σκοπός της μελέτης ήταν η καταγραφή της συχνότητας της αλλεργίας και τηςευαισθητοποίησης στο δηλητήριο της μέλισσας (HBV) και η ταυτοποίηση πιθανώνπαραγόντων κινδύνου. ∆ευτερεύων στόχος ήταν η διερεύνηση της πιθανήςσυσχέτισης των κλινικοεργαστηριακών παραμέτρων με την εμφάνιση ανοχής στο HBVσε αλλεργικούς μελισσοκόμους.Η μελέτη πραγματοποιήθηκε σε δυο φάσεις και συμπεριλήφθηκαν μέλημελισσοκομικών συνεταιρισμών από τη Βόρεια και τη Νότια Ελλάδα. Κατά την πρώτηεπίσκεψη, οι συμμετέχοντες αξιολογήθηκαν με: (α) ερωτηματολόγιο που αφορούσεδημογραφικά χαρακτηριστικά, πληροφορίες για τη μελισσοκομική δραστηριότητα,συμπτωματολογία μετά από φυσικούς νυγμούς και στοιχεία του ατομικούαναμνηστικού, (β) δερματικές δοκιμασίες νυγμού (∆∆Ν) και ενδοδερμικές δοκιμασίες(Ε∆) με κεκαθαρμένο εκχύλισμα HBV, (γ) αιμοληψία για τον προσδιορισμό στον ορότης ολικής ανοσοσφαιρίνης Ε (IgE), των ειδικών για το HBV IgE (sIgE-HBV) και IgG4(sIgG4-HBV) και της ισταμίνης σε επιλεγμένα δείγματα, και (δ) ∆∆Ν με μείζοναεισπνεόμενα και τροφικά αλλεργιογόνα για τον έλεγχο ατοπίας. Στη δεύτερησυνάντηση, δύο χρόνια μετά την πρώτη επίσκεψη, οι μελισσοκόμοι κλήθηκαν γιαεπανεξέταση και ερωτήθηκαν για τη συχνότητα των νυγμών και το είδος τωναντιδράσεων. Επίσης, έγινε επανάληψη των ∆∆Ν και Ε∆. Η στατιστική επεξεργασίατων δεδομένων έγινε με χρήση του IBM SPSS v.20.Τριακόσιοι εβδομήντα δύο μελισσοκόμοι (73,1% άνδρες), ηλικίας 45 ± 15 ετώνσυμπεριλήφθηκαν στη μελέτη. Αλλεργική αντίδραση μετά από νυγμό μέλισσαςανέφεραν 64 (17,4%) συμμετέχοντες. Θετικές δερματικές δοκιμασίες στο δηλητήριοτης μέλισσας διαπιστώθηκαν σε 81 (22,5%) άτομα, ενώ sIgE-HBV > 0.35 kU/Lανιχνεύθηκε σε 243 (65,3%) μελισσοκόμους. Σαράντα εννέα (76,6%) αλλεργικά άτομαανέφεραν εκ νέου νυγμούς μετά την αρχική αντίδραση, ενώ 38 (77,5%) από αυτούςείχαν παρουσιάζει ανοχή στο HBV. Η συχνότητα των ετήσιων νυγμών, ο νυγμός στηνκεφαλή, η ρινική συμπτωματολογία κατά την ενασχόληση με τα μελίσσια, το ιστορικόαλλεργίας στη σφήκα, καθώς και η συνύπαρξη θετικού ιστορικού ατοπίας και θετικών∆∆Ν σχετίζονταν θετικά (P < 0,05) με την εμφάνιση αλλεργικής αντίδρασης.Σημαντικές διαφορές (P < 0,05) παρατηρήθηκαν στα επίπεδα της sIgG4-HBV μεταξύαλλεργικών (15,9 ± 21,8 kU/L) και μη αλλεργικών (27,0 ±31,0 kU/L) ατόμων, καθώςκαι μεταξύ αλλεργικών που ξεπέρασαν (23,2 ± 24,6 kU/L) ή δεν ξεπέρασαν (3,0 ± 4,1kU/L) την αλλεργία στο HBV. Το 82,4% των συμμετεχόντων δήλωσε άγνοιααντιμετώπισης ενδεχόμενης αλλεργικής αντίδρασης. Για επανεξέταση προσήλθε το44,1% των μελισσοκόμων, στην πλειονότητα επαγγελματίες με μεγαλύτερη διάρκειαενασχόλησης με τη μελισσοκομία, που δέχονταν > 200 ετήσιους νυγμούς και κυρίωςμη αλλεργικοί ή αλλεργικοί που ξεπέρασαν την αλλεργία. Κατά την επανεξέταση, οιδερματικές δοκιμασίες στο HBV διαφοροποιήθηκαν σε 50 (31,5%) άτομα. Σε 11αλλεργικούς μελισσοκόμους, οι οποίοι πληρούσαν τα κριτήρια που τέθηκαν,προσδιορίστηκαν τα επίπεδα ισταμίνης στον ορό. Τα επίπεδα της ισταμίνηςπαρουσίασαν θετική συσχέτιση με τα επίπεδα της sIgG4-HBV. Οι τιμές των δύο αυτώνπαραμέτρων ήταν υψηλότερες στους αλλεργικούς μελισσοκόμους που ξεπέρασαν τηναλλεργία και σε αυτούς που είχαν > 200 ετήσιους νυγμούς.Συμπερασματικά, η συχνότητα της αλλεργίας και της ευαισθητοποίησης στοHBV ήταν αυξημένη στους μελισσοκόμους, ενώ αναγνωρίστηκαν παράγοντεςκινδύνου για την εμφάνιση αλλεργίας. Η ενημέρωση και εκπαίδευση αυτού του ειδικούπληθυσμού για τα μέτρα αντιμετώπισης της αναφυλαξίας είναι απολύτωςαπαραίτητες. Τα επίπεδα της sIgG4-HBV στον ορό συσχετίστηκαν τόσο με προστασίααπό την αλλεργία όσο και με αποδρομή της. Τέλος, τα επίπεδα της ισταμίνης στον ορότων αλλεργικών ατόμων ακολουθούσαν το ίδιο προφίλ με τα επίπεδα της sIgG4-HBV.Τα ευρήματα αυτά παραπέμπουν σε πιθανό ανοσορυθμιστικό ρόλο της ισταμίνηςστην εμφάνιση ανοχής έναντι των αλλεργιογόνων και χρήζουν περαιτέρωδιερεύνησης.

Dermanyssus gallinae (the poultry red mite, PRM) is an important ectoparasite in the laying hen industry. PRM can also infest humans, causing gamasoidosis, which is manifested as skin lesions characterized by rash and itching. Recently, there has been an increase in the reported number of human infestation cases with D. gallinae, mostly associated with the proliferation of pigeons in cities where they build their nests. The human form of the disease has not been linked to swallows (Hirundinidae) before. In this report, we describe an incident of human gamasoidosis linked to a nest of swallows built on the window ledge of an apartment in the island of Kefalonia, Greece. Mites were identified as D. gallinae using morphological keys and amplifying the Cytochrome C oxidase subunit I (COI) gene by PCR. Bayesian phylogenetic analysis and median-joining network supported the identification of three PRM haplogroups and the haplotype isolated from swallows was identical to three PRM sequences isolated from hens in Portugal. The patient was treated with topical corticosteroids, while the house was sprayed with deltamethrin. After one week, the mites disappeared and clinical symptoms subsided. The current study is the first report of human gamasoidosis from PRM found in swallows’ nest.

Allergen specific immunotherapy is the only disease-modifying treatment for allergic rhinoconjuctivitis and asthma. We present a rare clinical case of metrorrhagia as the major manifestation of anaphylaxis induced by subcutaneous immunotherapy to inhalant allergens.

Growing evidence identifies histamine as a key player in allergic responses, but the reports relating serum histamine to tolerance are scarce and inconclusive. This study investigated the relationship of circulating histamine to the tolerant phenotype in allergic beekeepers. The results showed a positive correlation between the serum levels of histamine and specific immunoglobulin G4 (sIgG4) to honeybee venom, but not with total IgE or sIgE. Interestingly, both sIgG4 and histamine levels were negatively correlated with the time since the last bee sting. In contrast to total IgE and sIgE, serum sIgG4 and histamine levels followed comparable patterns, being higher in tolerant/recently stung individuals and lower in the least frequently stung subgroup. The data obtained in this pilot study associated, for the first time, serum histamine levels with allergen tolerance in allergic individuals and provided the lead for further considering the putative immunomodulatory properties of histamine in allergic responses.

Background Food allergy (FA) represents a common and worldwide disorder but in publications referring to FA the reported diagnosis is rarely confirmed. Consequently, the subjectively assessed FA may negatively affect the quality of life of patients and their families. Objective We have conducted this internet survey in order to estimate the self-reported perception of FA in Greece. Methods A standard anonymous questionnaire was posted for a 3-month period on http://www.in.gr, a Greek popular Internet portal. Each individual could participate only once. Participants were screened for the presence or history of FA by a key question and were then asked to provide information on symptoms, course and management. Results A total of 3673 adult subjects (mean age 34.2 years, range 18–74, females 61.3%), reporting FA were included in analysis. Most reported reactions were related to fruits (14.9%), seafood (10.7%) and nuts (9.2%). The first episode occurred principally during the second (29.2%) and third (30.9%) decade within 3 h from consumption (82.2%). Predominant symptoms were urticaria and oral allergy syndrome (almost 25% each one). Nearly half of the participants sought no medical advice, while 31.4% asked for an allergist’s consultation. Almost 21% of reactors were hospitalized; nuts, severity of symptoms (lower respiratory and/or cardiovascular), onset in lower age, previous exercise and concomitant alcohol and/or aspirin intake were positively associated with hospitalization. Conclusion Although FA causes severe anaphylactic episodes, almost 50% of individuals who experience symptoms perceived as FA do not seek medical advice. Awareness programmes must be carried out in order to increase consciousness about this potentially fatal medical condition.

Background Urticaria is often underdiagnosed and/or undertreated. We have conducted an Internet-based study to record epidemiological and clinical features as well as therapeutic interventions for urticaria in a large sample of patients in Greece. Methods A standard anonymous questionnaire was posted for a 3-month period on ‘http://www.in.gr’, a Greek popular Internet portal. Each individual participated only once. Participants were screened for the presence or history of urticaria by two key questions and were then asked to provide information on symptomatology and management. Results A total of 12 396 subjects voluntarily responded to the survey, of which 8440 (5136 females) who reported to have or had urticaria, were finally analysed. A total of 4780 (56.6%) had experienced weals only, 507 (6.0%) angio-oedema only and 3018 (35.8%) both. Weals and angio-oedema were found to be more common in women; 2761(57.8%) and 277(54.6%), respectively. Age of onset significantly correlated with disease duration; a 1% higher possibility of longer duration of urticaria exists (more than 6 weeks compared with less than 6 weeks) for each additional year of age of onset after controlling for gender. Patients with chronic urticaria had increased mean age compared with those reporting the acute form (35.04 vs. 33.88 years, P

Background Physicians who practice alternative medicine often prescribe bee pollen as a food supplement and a treatment for various ailments. Objectives To determine the qualitative and quantitative composition of bee pollen and to investigate the cutaneous reactivity of atopic patients to bee pollen extracts. Methods The absolute number of pollen grains per gram of bee pollen was calculated, and morphologic identification of the botanical family was performed. Five extracts of bee pollen were prepared for skin prick testing, according to standard methods. Two hundred two volunteers participated in the study; 145 were atopic patients with respiratory allergy. The remaining 57 were healthy volunteers or nonatopic patients and served as a control group. All participants underwent skin prick testing with a standard battery of 6 aeroallergens (olive, grasses mix, Parietaria , mugwort, Dermatophagoides pteronyssinus , and Dermatophagoides farinae ) and with all homemade bee pollen extracts. Results All samples of bee pollen contained Oleaceae pollen in high concentrations. Small amounts of anemophilous pollen (Compositeae, Chenopodiaceae) were detected in various samples. A strong positive correlation was observed between cutaneous reactivity to bee pollen extracts and olive, grasses, and mugwort. Conclusions Bee pollen contains a large amount of pollen, which belongs to various allergenic families of plants. Bee pollen retains its allergenic potential as demonstrated by strong cutaneous responses to bee pollen extracts observed in atopic patients in contrast to nonatopic subjects. Regarding pollen allergic individuals, further studies are needed to evaluate the safety of ingesting large amounts of bee pollen.

Background Acute generalized exanthematous pustulosis (AGEP) is a rare and severe cutaneous reaction usually triggered by drugs. Other causative factors such as viral infections are rarely involved. In this study, we report a case of AGEP caused by a spider bite. Case Summary A 56-year-old woman was referred to the allergy unit after a spider bite at the left popliteal fossa, while gardening, 5 days earlier. The offending spider was captured and identified by an entomologist as belonging to the Loxosceles rufescens species. No acute reaction was observed; however, after 24 hours, due to the occurrence of typical dermonecrotic skin lesions associated with erythema and edema, Cefuroxime and Clindamycin were administered intramuscularly after medical advice was given. Almost 72 hours after the spider bite, an erythematous and partly edematous eruption appeared locally in the gluteus area bilaterally, which progressively expanded to the trunk, arms and femors. Within 24 hours dozens of small, pinhead sized, non- follicular pustules were present, mainly in the folds. The patient complained of a burning sensation of the skin in addition to pruritus; and simultaneously had a fever of 38-39 °C as the eruption expanded. Discussion A spider bite may represent a possible causative factor of AGEP. A spider's venom contains sphingomyelinase that stimulates the release of IL8 and GM-CSF, which are involved in AGEP pathogenesis. Whether or not the con-current use of antibiotics has an effect in AGEP appearance when combined with a spider's venom, cannot be excluded.

Allergic rhinitis is a global health problem which causes major illness and represents a risk factor for asthma. The primary aim of the study was to record the clinical pattern of allergic rhinitis and its temporal relation with asthma in a Greek population.Three-hundred and sixteen subjects with documented diagnosis of allergic rhinitis in a two-year period were included in this study. All participants completed a standardised questionnaire with full retrospective epidemiological data for rhinitis; in addition, serum IgE measurement and skin prick tests with 22 common inhalant allergens were carried out, while spirometry was performed in subjects with self-reported or doctor-diagnosed asthma. All subjects with at least one positive skin test were included in study analysis.One-hundred and sixty five out of 316 patients (49.1%) stated self reported-asthma while in 63/316 (19.9%) asthma was documented with spirometry. One hundred out of 165 (60.6%) had rhinitis as first clinical manifestation while in 24/165 (14.5%) asthma symptoms appeared first; the remaining 31/165 (24.9%) reported simultaneous onset of upper and lower airways' symptoms. About 68.5% were sensitised to seasonal allergens exclusively, while 50% were sensitised to ≥ 1 of Parietaria, grasses sp., Olea eur. The duration of rhinitis in the subpopulation of patients with self-reported asthma (n=165) was significantly higher compared with non-asthmatics (mean=3.22 years, p0.001). Survival analysis for the estimation of asthma onset showed that the mean time interval with rhinitis only is 16.6 years (median 12 years, incidence 0.0596).The unique environmental conditions and the aerobiology of each area clearly affect the clinical features of respiratory allergy.

Background Venom immunotherapy (VIT) is the only effective treatment for hymenoptera hypersensitivity, but conventional protocols require a few weeks. Objective We present the safety of a 3-day “rush” protocol that requires only 7 injections and 255 mgr cumulative dose before the 100 μg maintenance dose. Methods Forty-nine patients (33 males, 16 females) of mean age 43.57±12.9yrs received “rush” VIT. Only 7 injections were required until the maintenance dose of 100 mgr was reached on Day 5. On Day 1, four injections were administered with initial dose of 5 mgr and total dose of 75 μg. On Day 3 a cumulative dose of 180 mgr was administered in three injections (40 mgr, 60 mgr and 80 mgr). A dose of 100 mgr was administered on Day 5. Twenty-nine individuals were treated with Honey-Bee venom; 18 with Common wasp; 5 with Paper Wasp; while 13 patients received Mixed Vespid preparation. Inclusion criteria were documented IgE-mediated allergy with intradermal sensitivity to ≤0.1 mgr/ml venom concentration and concomitant detection of specific venom IgE ≥0.35 kU/l. Results All patients reached the maintenance dose. Forty-nine patients received 65 immunotherapy courses, resulting in 1520 injections. Thirty-three systemic reactions: 7 during building phase (1.5%); and 26 in the maintenance dose (2.4%) were observed in 9 patients. The percentage of reactions/total injection number was 2.2%; all reactions were mild-to-moderate. Fourteen patients reported documented field stings at least two months after VIT onset with only one reported mild systemic reaction. Conclusion We propose a simple “rush” VIT protocol in an outpatient setting as an easy-to-perform alternative option for VIT induction phase.