Analysis of mite allergic patients in a diverse territory by improved diagnostic tools.

BACKGROUND: There are few studies comparing the sensitization with mite allergens from different mite species which could potentially be the cause of allergy. OBJECTIVE: To improve the diagnosis of mite allergic patients from a diverse territory in which D. pteronyssinus/D. farinae mites together with storage mites could be present in the environment. METHODS: Four hundred and seventy-seven patients (both children and adults) from different regions, covering the main mite prevalent areas of Spain, were recruited. sIgE to eight allergens was measured together with SPT to whole mite extracts, level of mite allergen exposure, and specific IgG(4) . BAT and CAST was performed in a subgroup of patients. RESULTS: D. pteronyssinus and L. destructor were more prevalent in Atlantic areas, whereas D. farinae predominate in Mediterranean areas. About 90% of patients were sensitized to group 1 and/or group 2 allergens. Group 2 was the most prevalent, and the IgE response/intensity of sensitization in BAT was higher. sIgE to Der p 2/Der f 2 was almost fully cross-reactive, but no cross-reactivity was detected with Lep d 2. Group 1 allergens were also cross-reactive, but in some patients a species-specific response was observed. sIgE to Lep d 2 was associated with SPT results to storage mites. Sensitization to Der p 1 was more frequent in children, whereas Lep d 2 sensitization was more frequent in adults. A higher ratio IgE/IgG(4) to Der p 2 was associated with the presence of allergic asthma. CONCLUSION: An improved diagnosis algorithm has been established. Group 2 allergens seem to have a leading role in mite allergy, but as group 1 sensitization could be species-specific in some patients and its prevalence is higher in children, an adequate balance on major mite species and major allergens must be consider in the design of mite allergy vaccines.

Potential hypersensitivity due to the food or food additive content of medicinal products in Spain.

The Drug Allergy Committee of the Spanish Society of Allergology and Clinical Immunology reviewed the allergenic potential of several substances of food origin that are found in the composition of some drugs. Despite recent legislation on labeling, many labels do not clearly state whether the drug contains raw material (active ingredients, excipient, or other manufacturing intermediate) with an origin in any of the substances in the list of the 14 groups of food allergens that are subject to mandatory declaration. The objective of legislation is that the drug package, the Summary of Product Characteristics, and the patient information leaflet clearly state the food content in order to improve the safety of allergic patients. Therefore, any food or allergen derivative that must be declared should be clearly stated on the drug label. Of all the evaluated products, egg and milk derivatives are the most frequently discussed in literature reviews. The natural or synthetic origin of potentially allergenic substances such as lysozyme, casein, lactose, albumin, phosphatide, and aromatic essences should be clearly stated. Providing this information has 2 clear advantages. First, allergic reactions to drugs in patients with food allergy could be avoided (if the substances have a natural origin). Second, prescription would improve by not restricting drugs containing synthetic substances (which do not usually induce allergic reactions).

Depigmented and polymerised house dust mite allergoid: allergen content, induction of IgG4 and clinical response.

BACKGROUND: Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study. METHODS: Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients' sera using the CAP system and direct ELISA experiments. RESULTS: Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment. CONCLUSIONS: The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts.

Assessment of a new brand of determinants for skin testing in a large group of patients with suspected beta-lactam allergy.

BACKGROUND: Skin testing with major and minor determinants of benzylpenicillin is recommended standard practice for the evaluation of patients with immediate hypersensitivity reactions to beta-lactams. However, commercial reagents for this purpose were recently dropped from the European market. OBJECTIVE: In the present study, we assessed a new brand of reagents for use in skin testing in patients with suspected penicillin allergy. METHODS: Prick tests and intradermal tests were performed with benzylpenicilloyl polylysine (PPL) and minor determinant mixture (MDM). Penicillin G, amoxicillin, and the culprit beta-lactam were also tested. If skin tests were negative, a single-blind oral challenge test was performed with the culprit active principle or penicillin. If both skin tests and challenge tests were negative, the same procedure was repeated between 2 and 4 weeks later. RESULTS: A total of 636 patients were assessed. The allergy study was positive in 69 patients. Skin tests with PPL were positive in 30 patients (46.8%) and with MDM in 28 (43.7%). Sixteen patients displayed a positive reaction to both PPL and MDM (25%), while 42 patients (65.6%) had a positive reaction to either PPL or MDM alone. Thirty-two patients had positive skin test reactions to penicillin G or another p-lactam antibiotic. Five patients in whom a negative result was obtained in skin tests had a positive reaction to oral challenge. CONCLUSIONS: Our results indicate that a new brand of determinants that is commercially available in Europe is a reliable and useful tool for the diagnosis of beta-lactam allergy. The new reagents are a safe alternative to the previously available brand.

Extracts from various mite species contain cross-reactive and noncross-reactive IgE epitopes. A RAST inhibition study.

Previous studies have demonstrated the high incidence of Dermatophagoides, Euroglyphus, Blomia, Lepidoglyphus and Chortoglyphus spp. sensitizations in a mite-allergic population. The aim of this study was to evaluate immunological cross-reactivity among the above mentioned groups, using sera from a nonrural population allergic to mites, from a subtropical area (Canary Islands). RAST inhibition studies demonstrated significant cross-reactivity among Dermatophagoides and Euroglyphus species (> or = 65% of maximum theoretical inhibition), as also noted by other authors. Blomia kulagini demonstrated scarce cross-reactivity with Dermatophagoides, Lepidoglyphus and Chortoglyphus species (< or = 30% of maximum theoretical inhibition) and medium level with Euroglyphus maynei (45% of maximum theoretical inhibition). Chortoglyphus arquatus demonstrated high cross-reactivity levels with the other species studied. The results obtained in this study demonstrated the scarce immunological cross-reactivity between Pyroglyphidae and non-Pyroglyphidae mites, thus suggesting the polysensitization of the studied population to different mite species.

Olerance of a cluster schedule with a house dust mite extract quantified in mass units: multicentre study.

The standardisation of allergenic extracts in micrograms of the major allergen has encouraged the search for new treatment schedules, with the purpose of shortening the number of visits and doses required to reach the maintenance dose without eliciting a greater risk of adverse reactions for the patients. With this objective, a prospective multicentre pharmacovigilance study was designed that included 200 patient with allergic rhinoconjunctivitis and/or allergic asthma sensitised to mites (Dermatophagoides pteronyssinu and/or farinae). The dose increment period was carried out using a cluster schedule, where the optimal dose wa reached after 4 visits, administering two doses in each visit. The duration of the study was 5 months and a total o 1902 doses were administered. At the end of the trial, 31 adverse reactions in 23 patients were recorded. Six of these were systemic (0.3% of t administered doses) recorded in 6 patients (3% of the sample). One was an immediate reaction (grade 1) and delayed (4 mild and 1 moderate). Two were asthmatic exacerbations, 2 cutaneous reactions, 1 rhinitis and 1 an unspecific symptom (not IgE-mediated). Two appeared upon administration of the first vial and the remaining 4 after administration of the third cluster. Therefore, the schedule tested presents an adequate tolerance profile, suggesting savings (compared to th conventional schedule of 13 doses per patient) of 1800 visits and 1000 treatment doses in the whole study.

Clinical cross-reactivity between Artemisia vulgaris and Matricaria chamomilla (chamomile).

Artemisia vulgaris is a common weed and an important source of allergens on the subtropical island of Tenerife, Canary Islands, Spain. It pollinates mainly from July to September, although, due to some local climatic conditions, it may flower throughout the year. Cross-reactivity with hazelnut, kiwi, birch, several Compositae (Ambrosia, Chrysanthemum, Matricaria, Solidago) and grass allergens has been suggested. Few studies have addressed the issue of in vivo cross-reactivity between A. vulgaris and Matricaria chamomilla. The objective of this study was to perform conjunctival and bronchial challenges with A. vulgaris and M. chamomilla and oral challenge with chamomile in 24 patients with asthma and/or rhinitis sensitized primarily to A. vulgaris. Skin prick tests with M. chamomilla were positive in 21 patients. Eighteen patients had a positive conjunctival provocation test with a A. vulgaris pollen extract and 13 patients had a positive conjunctival provocation test with a M. chamomilla pollen extract. Bronchial provocation tests with A. vulgaris were positive in 15 patients and with M. chamomilla pollen in another 16 individuals. Oral provocation tests, conducted with a commercial chamomile infusion were positive in 13 patients. Nine of these individuals were skin test positive to food allergens and 17 to others pollens of the Compositae family. This study confirms a high degree of in vivo cross-reactivity between A. vulgaris and M. chamomilla. Sensitization to A. vulgaris seems to be a primary risk factor for experiencing symptoms after the ingestion of chamomile infusions. Based on the results of bronchial provocation tests, M. chamomilla pollen could be a relevant inhalant allergen.

Epidemiology of allergic reactions in beekeepers: a lower prevalence in subjects with more than 5 years exposure.

Beekeepers (Bks) represent a high allergic risk population against Hymenoptera because of their frequent exposure to bee stings. Most published studies show different percentage of sensitization and systemic reactions with to another groups of population. With the aim to know the prevalence and type of allergic reaction in Bks from the Canary Islands, 246 subjects were studied prospectively. A questionnaire was developed and skin test and specific IgE determination against Apis mellifera, Vespula and Polistes venom were performed. One hundred and twenty eight subjects had presented at least one reaction greater than merely local. In 83.5% of these subjects subsequent stings caused reactions of lesser intensity. Specific IgE in serum for Apis mellifera was positive in 126 BKs, for Vespula in 27 and for Polistes in 9. We found that the group of BKs sensitized to Apis was significantly higher among atopics BKs (p < 0.001) and with fewest years of working experience in beekeeping (p = 0.0134). This study showed that sensitization to Hymenoptera is higher in beekeepers with less than 5 years working experience and who are sensitized to another allergens.

The natural history of Apis-specific IgG and IgG4 in beekeepers.

BACKGROUND: Most published studies on changes of specific IgG or its subclasses as a response to stimuli by allergens have been performed on patients under immunotherapy. There are few reports analysing the response to immunoglobulins in patients exposed to allergens in their natural habitats. OBJECTIVE: The aim of this work was to discover the natural history of Apis specific IgG (IgG-ap) and IgG4 (IgG4-ap) levels in beekeepers from the Canary Islands. METHODS: We studied 242 beekeepers (Bks). We used a questionnaire and measured total IgE and seric Apis specific IgE (IgE-ap), IgG-ap and IgG4-ap against Apis mellifera venom. RESULTS: All Bks had IgG-ap and IgG4-ap. IgE-ap was positive in 160 Bks (65.6%), but only 92 (37.6%) Bks were considered sensitized. IgG-ap and IgG4-ap showed significant correlation (r = 0.84); IgE did not correlate with IgG-ap or IgG4-ap. There was no seasonal variation in IgG-ap or IgG4-ap. The group of sensitized Bks had significantly lower IgG-ap and IgG4-ap levels (P < 0.05). The groups with longer beekeeping activity showed significantly higher levels of IgG-ap and IgG4-ap (P < 0.001). Bks with locals reactions had significantly higher IgG-ap and IgG4-ap than Bks who reported systemic reactions (P < 0.05). CONCLUSION: Our study showed that IgG-ap and IgG4-ap appear to increase in Bks, either according to their beekeeping experience or in subjects with local reactions after bee stings.

Sensitization to Blomia kulagini in a general population of a subtropical region of Spain (Canary Islands).

The Blomia genus has been described as allergenic in man. The present study aimed to assess the prevalence of B. kulagini sensitization in a large population of allergic subjects without occupational exposure in a subtropical region (Canary Islands, Spain). Secondarily, a new standardized B. kulagini extract was evaluated. The study population comprised 207 patients. RAST for B. kulagini was positive in 76.2% of patients, and 47 of them were selected for the biologic standardization. When the prick test was performed with the nonstandardized extracts, results were positive in 76.6%, whereas when the test was repeated with the standardized extract, sensitivity rose to 95.7%. The conjunctival provocation test was positive in 78.3% of 46 evaluated patients. The bronchial provocation test was positive in 18 sensitized patients and negative in five controls. In conclusion, B. kulagini is an important cause of sensitization among the occupationally unexposed population of the studied area and should be included in allergy diagnostic tests. For reliable prick tests, the use of standardized extracts is mandatory.

Hyper-IgE syndrome. Presentation of three cases.

Three cases of Hyper-IgE syndrome are herein described, corresponding to patients aged six, twelve and 4 years, who from infancy, had suffered a variety of recurrent pulmonary infections, staphylococcal cold abscesses and chronic dermatitis. IgE counts were superior to 2.000 u/ml and eosinophilia surpassed 0.6 x 10(9) cells/l in all three cases. Deficits in the mytogen and chemotaxis responses were also seen. These patients were treated with I.V. gammaglobulin, anti-biotherapy and ascorbic acid. The possible physiopathology of this syndrome and its association with different alterations to pulmonary immunity are discussed in this paper. Hyper-IgE Syndrome is characterized by recurrent dermal and pulmonary infections (pneumonia and abscesses), dominated by elevated IgE levels, and in 1974, this Syndrome was included within the "immunodeficiencies" group, and Hill and Quie described this as a process involving recurrent bacterial infections and eczemas accompanied by elevated IgE levels, together with a defect in the mobility of neutrophils. Previously, in 1966, Job described this Syndrome in fair-skinned, red-headed young girls, suffering from eczemas and recurrent cold abscesses of staphylococcal ethiology, found on the skin, in subcutaneous tissue cells and lymph nodes. Later, Dr. Buckley defined this Syndrome by an increase in serum IgE levels, chronic dermatitis and severe repetitive infections. This Syndrome today, is still an immunological mystery, defined by two clinically compatible criteria and an increase in IgE. Other analytical abnormalities, including neutrophilic mobility, the appearance of IgE antibodies anti-Candida or staphylococcus, are non-constant findings.

The capturing of pollens in the atmosphere of La Laguna City, Tenerife, Canary Islands 1990-1995.

This paper forms part of a Doctorate Thesis, carried out in the Allergy and Immunology Department of the Nuestra Señora de la Candelaria Hospital, Tenerife, entitled "Epidemiology of Pollens on the Island of Tenerife. Allergy to Pollen". This paper deals with the capturing of pollen in the atmosphere of the city of La Laguna, Tenerife, during the period 1990-1995, and demonstrates that the Occidental Islands of the Canarian Archipelago are similar to a miniature continent with a special microclimate and a large amount of vegetation, where all classes of pollen can be found given the large variety of plants and trees including native species. High concentrations of more than 50 grains of pollen per m3 can be found in the air of the Occidental Islands, above all wild grasses, cultivated grasses, weeds, Artemisa vulgaris, Parietaria officinalis and Plantago lanceolata, and in a lowe proportion, Cupressaceae, Pinaceas, Mercurialis and Rumex. We have pollen concentrations very similar to other parts of the continent.

A prospective and multicenter safety-monitoring study of a short up-dosing schedule of immunotherapy with a mass-units-standardized extract of mites.

A prospective, multicenter pharmacovigilance study was carried out to evaluate the safety of a new 7-dose treatment schedule of subcutaneous immunotherapy as opposed to the conventional 13 doses normally recommended. The study was carried out in 14 centers and included 261 patients (children and adults) with respiratory allergic disease due to sensitization to mites (Dermatophagoides pteronyssinus and/or farinae). A total of 2290 doses were administered under the direct supervision of the participating specialists. One hundred and ten reactions in 63 patients (24.1%) were recorded, representing 4.8% of the total doses administered. Most of the reactions (98) were local. Only 12 were systemic (0.5% of the administered doses) and occurred in 10 patients (3.8% of the sample). Ten reactions reverted quickly with rescue medication. The maintenance dose had to be lowered in one patient and another patient was withdrawn from the study after suffering two asthmatic crises after two consecutive doses. In view of the results obtained, we can conclude that the new schedule shows an acceptable tolerance profile and does not present a greater risk of reactions than the conventional scheme of 13 doses using an identical extract. Moreover, the new schedule represents substantial savings in the number of doses and visits required to reach the maintenance dose.

House dust mites and Der p I in Tenerife (Canary Islands, Spain): the relative importance of other non Dermatophagoides spp mites.

BACKGROUND: House dust mites constitute the major etiologic factor causing sensitization and asthma its geographical distribution map is quite well known, although it is not yet complete. Home environments world-wide show mites that mainly belong to the Piroglyphidae family, the D. pteronyssinus specie being the predominant one. However others have also been considered of interest. OBJECTIVE: The aim of this work was to study the species and to determine the levels of Der p I, Der f I and group II of allergens of Dermatophagoides. Present in houses from Tenerife, Canary Islands (Spain). METHODS: Dust samples were collected in 130 houses. RESULTS: D. pteronyssinus was found in 121 (95.3%) homes, being the predominant species in 113 (89%). In 69 (55%) homes, Dermatophagoides spp. were found together with other species from other generus. Mean values for Der p I were 13.7 +/- 13.88 (mean +/- SD), for Der f 1 1.05 +/- 1.83 and for the Group I of allergens 7 +/- 6.77. CONCLUSION: Although D. pteronyssinus is the predominant species in our area, there are others that may be off importance and should be taken into consideration in the diagnostic, home disallergenization and later treatment of patients.