Safety and Efficacy of a Progressively Prolonged Maintenance Interval of Venom Immunotherapy.

BACKGROUND: The long-term protection provided by venom immunotherapy (VIT) is related to the dose administered and to its long duration; the latter, however, becomes inconvenient for patients in countries like Greece, with many islanders or inhabitants of distant mountainous areas. Maintenance interval prolongation reduces the number of office visits - saving time and money - and as a consequence contributes to the patients' compliance. The aim of this prospective study was to evaluate the safety and efficacy of VIT on a progressively prolonged maintenance interval (PPMI). METHOD: 450 venom-allergic patients were reviewed for participation in our study; all of them were initially treated with a modified rush or an ultrarush protocol using freshly reconstituted, pure venoms. Upon reaching the maintenance dose, the VIT interval was scheduled to be gradually prolonged - by 1 week each time - aiming at a maximal interval of 26 weeks. RESULTS: 267/450 patients consented to participate in our VIT PPMI protocol: 98 were treated with vespid(s) venom, 142 with honeybee venom, and 27 with both. The mean duration of patient follow-up was 9.1 ± 4.2 years. The majority of systemic reactions due to VIT injections occurred up to the 8-weeks PPMI; few additional reactions were documented in a small fraction (2.9%) of our patient population beyond 9 weeks and up to 16 weeks; all were caused by honeybee VIT. No reactions were observed during VIT administration at the 26-week interval. Ninety-six patients reported 204 field sting occurrences by the culprit insect. Ten systemic reactions (8 mild and 2 moderate in severity) were registered between the 9- and 18-week PPMI; the honeybee was the culprit insect in all cases. 108 field stings by the offending insect were sustained beyond the 20- and up to the 26-week PPMI; there were no reactions at all. CONCLUSIONS: Progressively prolonging the VIT maintenance interval up to 26 weeks appears to be safe and efficacious.

Anaphylaxis during skin testing with food allergens in children.

Skin testing is the diagnostic cornerstone for allergies and is considered extremely safe. It is usually performed with the prick and the prick-to-prick method. The aim of this study is to report the first two pediatric cases of systemic allergic reactions during skin prick tests (SPT) with commercial food allergens. Both patients had a history of fish allergy. A 5-year-old girl, with a history of atopic dermatitis and asthma, reported an episode of urticaria and angioedema due to ingestion of fish, which had occurred 2 years before consultation. Ten minutes after having completed SPT to fish extracts, which had resulted positive, she suffered from generalized pruritus, nausea, stomach pain, and loss of consciousness. A 9-year-old boy, with a history of asthma and two episodes of acute urticaria and angioedema upon eating fish during infancy, reported a recent episode of oropharyngeal pruritus after tasting salmon. He was evaluated for fish allergy with SPT but developed conjunctivitis and acute urticaria during the first 10 min of the test. Anaphylaxis appears to be a rare side effect of skin testing in pediatric patients. Children with a history of asthma and atopic dermatitis are more likely to react.

Bronchial hyperresponsiveness in patients with cholinergic urticaria.

BACKGROUND: Cholinergic urticaria is occasionally associated with bronchospasm, even in patients without a history of asthma; the underlying mechanism has not been elucidated. OBJECTIVE: To evaluate bronchial hyperresponsiveness (BHR) in patients with cholinergic urticaria compared with healthy adults and patients with chronic urticaria. METHODS: Patients with a history of cholinergic urticaria and a positive ergometric test result constitute the study group. History was reviewed and physical examination and spirometry were performed to exclude exercise-induced anaphylaxis and exercise-induced asthma. Patients with chronic urticaria and healthy volunteers were used as positive and negative controls, respectively. All 3 groups were evaluated for BHR using a methacholine challenge test. RESULTS: Fifty-nine adults participated in the study: 30 patients with cholinergic urticaria, 15 with chronic urticaria, and 14 healthy volunteers. BHR was demonstrated in 13 of 30 patients (43%) in the study group, 1 of 15 patients with chronic urticaria (7%), and 1 of 14 healthy volunteers (7%); the observed difference was statistically significant. Further analysis of the study group demonstrated the existence of 2 subpopulations of patients with cholinergic urticaria, which were discriminated on the basis of intensity and duration of symptoms, with 96.7% accuracy. In addition, a statistically significant correlation was found between patient age and disease duration and between intensity and frequency of symptoms. CONCLUSIONS: Evaluation of patients with cholinergic urticaria should probably include BHR. A formula based on duration and intensity of cholinergic urticaria symptoms is provided as a tool for the prediction of BHR.

Bee pollen sensitivity in airborne pollen allergic individuals.

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.

Mold allergy in the Mediterranean Island of Crete, Greece: a 10-year volumetric, aerobiological study with dermal sensitization correlations.

Mold spores are universal outdoor and indoor components and generally are recognized as possible sources of respiratory allergies. A 10-year aerobiological study (1994-2003) was conducted in the city of Heraklion located at the center of the Mediterranean island of Crete, Greece. Eighteen mold species exhibiting a normal annual seasonal pattern have been identified and recorded. The most abundant mold species include (a) Cladosporium, (b) Alternaria, (c) miscellaneous ascosporas (d) Leptosphaeria, and (e) basidiomycete Coprinus. In parallel, 571 atopic individuals were tested by skin-prick tests (SPTs). Among these 571 patients 42.5% showed dermal positivity to mold allergens. Most positive SPTs were those of (a) Alternaria, (b) Cladosporium, (c) Fusarium, (d) Aspergillus, and (e) Mucor. No linear relationship was noted between SPT frequencies and percentages of mold species. All of these aerobiological and sensitization data constitute a firm basis for further medical and biological research and application.

A 10-year aerobiological study (1994-2003) in the Mediterranean island of Crete, Greece: grasses and other weeds, aerobiological data, and botanical and clinical correlations.

Grasses and weeds contain species that produce abundant pollen grains and have been implicated as causative agents in both asthma and allergic rhinitis. In this study, we present the pollen counts of allergenic grasses and weeds on the island of Crete and show their impact on allergic individuals. Heraklion is located at the center of the north shore of Crete and has been monitored with a Burkard 7-day volumetric spore trap since 1994, to determine the identity, concentration, and seasonal variation of airborne pollen grains. Data from 10 consecutive years were recorded, analyzed, and correlated to the growth of respective plants on this island. The island's vegetation and blossoming periods have been investigated by conducting field trips. In parallel, an atopic population of 576 individuals with a convincing history of allergic respiratory disease-rhinitis and/or asthma-was subjected to skin-prick tests with 50 common allergens. Quantitatively, there was a fair agreement between total pollen counts and positive skin-prick test frequencies for Parietaria (Urticaceae family). For the majority of the grass and weed genera, strongly positive skin test responses were observed frequently, despite rather low pollen counts.

Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic treatment for moderate/severe seasonal allergic rhinitis.

BACKGROUND: The preventive use of medications has been proposed to be effective in the treatment of seasonal rhinitis. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate and nedocromil sodium nasal sprays as prophylactic treatment for moderate to severe seasonal allergic rhinitis (SAR). PATIENTS: Sixty-one patients were recruited from 3 referral allergy centers. Inclusion criteria were history of SAR for 2 years or longer, sensitization to relevant local pollen (grasses, Parietaria, and olive), and age older than 12 years. METHODS: An open-label, randomized, parallel-group, "real-life" study design was used. Patients received mometasone furoate nasal spray once daily or nedocromil sodium nasal spray 3 times daily starting 2 to 4 weeks before the pollen season and continuing for up to 4 months. Instructions regarding the use of additional medications were given. Diary cards recording symptoms, use of medication, and adverse events were kept by the patients. RESULTS: All 61 patients completed the study. The prophylactic use of mometasone furoate vs nedocromil sodium led to significantly more days without symptoms (75.1% vs 54.5%; P < .001). The mometasone furoate group also had lower nasal symptom scores (mean, 1.4 vs 2.9; median, 0 vs 2; P < .001) and was more satisfied (93.1% vs 43.5%; P < .001). No serious adverse event was recorded, and there was no difference between the treatments in any adverse event. CONCLUSIONS: Prophylactic administration of mometasone furoate before the pollen season is safe and may lead to improved control of SAR compared with the use of nedocromil sodium.

Acute ST-segment elevation myocardial infarction after amoxycillin-induced anaphylactic shock in a young adult with normal coronary arteries: a case report.

BACKGROUND: Acute myocardial infarction (MI) following anaphylaxis is rare, especially in subjects with normal coronary arteries. The exact pathogenetic mechanism of MI in anaphylaxis remains unclear. CASE PRESENTATION: The case of a 32-year-old asthmatic male with systemic anaphylaxis, due to oral intake of 500 mg amoxycillin, complicated by acute ST-elevation MI is the subject of this report. Following admission to the local Health Center and almost simultaneously with the second dose of subcutaneous epinephrine (0.2 mg), the patient developed acute myocardial injury. Coronary arteriography, performed before discharge, showed no evidence of obstructive coronary artery disease. In vivo allergological evaluation disclosed strong sensitivity to amoxycillin and the minor (allergenic) determinants of penicillin. CONCLUSION: Acute ST-elevation MI is a rare but potential complication of anaphylactic reactions, even in young adults with normal coronary arteries. Coronary artery spasm appears to be the main causative mechanism of MI in the setting of "cardiac anaphylaxis". However, on top of the vasoactive reaction, a thrombotic occlusion, induced by mast cell-derived mediators and facilitated by prolonged hypotension, cannot be excluded as a possible contributory factor.

Multiple physical urticarias: report of three cases and review of the literature.

The appearance of more than one physical urticaria (PU) in the same patient has been documented; cold urticaria or dermatographism in association with some other type of PU are encountered more frequently. Three female patients exhibiting multiple PUs simultaneously are presented. In one female patient four different forms of PU could be shown with the appropriate challenge tests; the other two female patients exhibited five different types. The longest postdiagnosis follow-up, with objective evaluation and persistence of all PUs, was 6 years in one subject. The co-occurrence of two, three, or four PU types has been published in the relative literature; no cases of five PUs have been reported previously.

Patients with negative skin tests.

PURPOSE OF REVIEW: The aim of this article is to present and discuss the clinical problem of systemic anaphylaxis to Hymenoptera venoms in patients without detectable immunoglobulin E, as it appears in recent literature. Reported at variable frequency in large series of patients undergoing evaluation, systemic anaphylaxis was previously considered to reflect lost sensitization or to involve non-immunoglobulin E mediated mechanisms. Sporadic case-reports drew attention to the fact that severe or even fatal reactions may occur in patients with negative skin tests. RECENT FINDINGS: A breakthrough article by Golden et al., who performed deliberate stings on skin test negative venom anaphylaxis patients, demonstrated that clinical sensitivity was still present in a subset of these subjects and pointed out to the limitations of present diagnostic methods or reagents. New immunobiochemical methods and highly specific recombinant allergens--when all clinically relevant Hymenoptera venom allergens have been identified, cloned, sequenced and expressed in the proper system--are anticipated to increase the diagnostic yield. Non-specific mechanisms causing anaphylactoid reactions will probably explain some enigmatic, skin test negative radioallergosorbent test negative cases in the future. Occult mastocytosis, predisposing patients to anaphylactoid reactions, has been reported with increasing frequency among skin test negative patients. Lastly, other causes mimicking venom anaphylaxis may on rare occasions contribute to the problem. SUMMARY: With the present understanding of venom allergy, the practising clinician is not infrequently faced with the dilemma of the skin test negative patient. Once other identifiable causes have been carefully ruled out, referral to a specialized center for deliberate sting-challenges appears in selected cases to be a medically appropriate and ethically justified management approach.