Steps towards clarifying the clinical relevance of minor olive allergens in areas with extremely high levels of olive pollen

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Challenge-based clinical patterns of 223 Spanish patients with nonsteroidal anti-inflammatory-drug-induced-reactions.

BACKGROUND: The single-blind, placebo controlled oral challenge (SBPCOC) is the definitive way to diagnosis nonsteroidal anti-inflammatory drug (NSAID)-induced reactions. OBJECTIVE: To evaluate 223 NSAID-sensitive patients by means of SBPCOC, and to describe the main clinical patterns found. METHODS: A prospective study was carried out, including 2 patient groups with case histories consistent with NSAID-induced reactions. Of the 223 patients, 174 were diagnosed on the basis of a positive SBPCOC. The second group consisted of 49 patients who were referred because of a documented history of anaphylaxis after taking NSAIDs, and these underwent SBPCOC with potent cyclooxygenase (COX)-1/COX-2 inhibitors, except those reported as being responsible for the reaction. The type of SBPCOC reaction, the NSAID reactivity pattern, and the associated diseases were the main classification criteria. RESULTS: Two broad categories of NSAID-induced reactions were identified: the cross-reactive and selective syndromes. The 150 patients who showed cross-reactive syndromes included 3 types of diseases: type 1, patients with rhinitis and/or asthma who developed nasoocular and/or asthmatic reactions (n=40); type 2, patients with or without chronic urticaria who presented urticaria/angioedema (n=59); and type 3, atopic patients with isolated periorbital angioedema (n=51). In contrast, the selective syndromes, or type 4, included 50 patients who developed anaphylaxis, as well as 11 patients with urticaria during SBPCOC. Finally, a miscellaneous group of reactions not matching any of the above types was identified (n=1 2). CONCLUSIONS: NSAID-sensitive patients can be classified into 4 different groups of reactors, each with well-defined clinical characteristics. Thus, a clinical classification of this NSAID-induced reaction complex is proposed.

An occupational respiratory allergy caused by Sinapis alba pollen in olive farmers.

BACKGROUND: Sinapis alba (white mustard) is a entomophilic species included in the Brassicaceae family. To date it has not been related to allergic sensitization or clinical respiratory disease. METHODS: Twelve olive orchard workers had a history of rhinitis and/or bronchial asthma that occurred during control weed management and/or harvest, from January to March. They underwent skin prick tests (SPT) with S. alba pollen extract and a standard battery of aeroallergens. Sinapis alba pollen extract was prepared for performing quantitative skin tests, enzyme allergosorbent test and nasal challenge test (NCT). A portable monitoring station and an urban volumetric Hirst-type spore trap were used for the aerobiological study. RESULTS: Eleven patients suffered from rhinitis and bronchial asthma and one had only from rhinitis. All patients were sensitized to S. alba pollen extract, and they showed a positive NCT response. In the urban aerobiologic monitoring station the amount of S. alba pollen only exceptionally reached peaks of 21 grains/m(3), whereas in the work environment peaks of 1801 grains/m(3) were detected between 15 February and 7 April. CONCLUSIONS: We demonstrate the existence of a new occupational allergen for olive farmers: S. alba pollen. We point out the importance of perform aerobiological sampling within the occupational environment for the detection and quantification of the allergenic source.

Ole e 2 and Ole e 10: new clinical aspects and genetic restrictions in olive pollen allergy.

BACKGROUND: The clinical characteristics in olive pollen allergy are dependent on the antigenic load, the allergens profile, and the genetic restrictions. Our objective was to determine specific response pattern in Ole e 2 and Ole e 10 sensitization at those levels. METHODS: We studied 146 patients with seasonal rhinitis and/or asthma and positive prick test to Olea europaea pollen. IgE against Ole e 2 and Ole e 10 were detected by skin prick test and ELISA. HLA-DRB1 and HLA-DQB1 loci were typed by polymerase chain reaction sequence-specific primers method. RESULTS: A total of 102 (69.9%) and 79 (54.0%) patients showed significant IgE antibody response against Ole e 2 and Ole e 10, respectively. There was a significant association between Ole e 2 (OR 2.2, P = 0.04) and Ole e 10 reactivities (OR 2.8, P = 0.007) with asthma. In addition, total and specific IgE antibody levels significantly correlated with asthma (P < 0.05). Patients who reacted to both allergens reached the highest asthma risk factor (OR 4.3, P = 0.002). Phenotypic frequency of DR7 (OR 5.4, Pc = 0.003) and DQ2 (OR 3.6, Pc = 0.02) were increased in positive Ole e 2 patients compared with control subjects. DR2(15) phenotypic frequency was significantly increased (OR 5.6, Pc = 0.02) in positive Ole e 10 patients compared with control subjects. CONCLUSIONS: Our data suggest an association of Ole e 2 and Ole e 10 with bronchial asthma. Also, we found a genetic control of Ole e 2 and Ole e 10 IgE-specific responses that could be relevant to clinical disease in olive pollen allergy.

Alergia a alimentos de origen vegetal en una población adulta de la provincia de Jaén / Plant-derived food allergy in an adult population of Jaen

Antecedentes: El espectro clínico de la alergia a alimentos de origen vegetal engloba entidades que van desde el síndrome de alergia oral hasta la anafilaxia.Objetivo: Estudiar las características clínicas de una población de pacientes adultos con reacciones inducidas por alimentos de origen vegetal. Metodología: Se incluyeron 195 pacientes que cumplían los siguientes criterios: 1) Anamnesis sugestiva (urticaria/angioedema, síndrome alergia oral (SAO) o anafilaxia) inducida tras el consumo de alimentos vegetales y 2) pruebas cutáneas positivas a la fruta implicada en la anamnesis. Las variables principales analizadas fueron: la especie de vegetal, el tipo de reacción y la existencia de otras enfermedades atópicas, como la polinosis y la alergia al látex. Ese utilizó la prueba de X2 para detectar las diferencias significativas entre los subgrupos de pacientes.Resultados: Se incluyó en el estudio a 73 varones (37,4 por ciento) y 122 mujeres (62,6 por ciento) con edades comprendidas entre 14 y 67 años. Se estudiaron 527 episodios de reacciones a frutas pertenecientes a 25 especies diferentes. La familia Rosaceae ha sido la más implicada, especialmente el melocotón (51,2 por ciento), seguida de Cucurbitaceae (melón 29,2 por ciento) y Actinidiaceae (kiwi 28,2 por ciento). La reacción urticarial (41,5 por ciento), el síndrome de alergia oral (35,4 por ciento) y la anafilaxia (23,1 por ciento) fueron las manifestaciones clínicas más frecuentes. La anafilaxia se asoció significativamente (39 por ciento frente a 18,8 por ciento; X2 p<0,01) a pacientes no polínicos. El SAO se asoció significativamente (59,4 por ciento frente a 14,6 por ciento; X2 p<0,01) a la existencia de polinosis. Treinta y nueve pacientes (20 por ciento) presentaron alergia al látex. En este subgrupo se demostró una asociación significativa a la castaña (56 por ciento frente a 18,5 por ciento;X2 p<0,001), el plátano (46 por ciento frente a 21,1 por ciento; X2 p<0,001) y al aguacate (12,8 por ciento frente a 3,2 por ciento, X2 p <0,05). Por último, nueve alimentos (melón, pistacho, higo, semilla de girasol, melocotón, avellana y almendra) mostraron una asociación significativa a, al menos, una polinosis específica.Conclusión: La alergia a alimentos de origen vegetal en una población adulta tiene manifestaciones clínicas heterogéneas y las diferentes formas clínicas muestran asociaciones variables y muy definidas con diferentes polinosis (AU)

Olive allergen-specific IgE responses in patients with Olea europaea pollinosis.

BACKGROUND: Olive tree (Olea europaea) pollen is an important cause of pollinosis in the countries of the Mediterranean area. OBJECTIVE: This work aimed to study the IgE-binding frequency of Ole e 1, Ole e 2, Ole e 3, Ole e 6 and Ole e 7 from O. europaea pollen in a large population of olive pollen-allergic patients. METHODS: We studied: 119 consecutive patients with seasonal rhinitis and/or asthma and a positive skin prick test to O. europaea pollen extract; 10 atopic patients without history of pollinosis and a negative skin prick test to O. europaea; and 10 healthy controls. Allergens were purified from O. europaea pollen extract by reverse phase HPLC and characterized by N-terminal amino acid sequencing, MALDI analysis, and specific IgE immunodetection. Skin prick tests and ELISA titration against above mentioned purified olive pollen allergens were performed in all pollinic patients and controls. RESULTS: One-hundred and seven (90.7%) patients had a positive skin response to Ole e 1; 88 (74.6%) reacted to Ole e 2; 57 (47.9%) reacted to both Ole e 6 and Ole e 7; and 43 (37.8%) reacted to Ole e 3. The allergenic activity determined by ELISA to Ole e 1 was found in 84%; to Ole e 2 in 61.3%; to Ole e 3 in 31.9%; to Ole e 6 in 39.4%; and to Ole e 7 in 41.2% of patients. All patients had positive skin responses to at least one of the allergens tested, However, a combination of Ole e 1 and Ole e 2 together with a minor allergen Ole e 6 or Ole e 7, disclosed the same diagnostic value that was obtained with the use of crude olive pollen extract. The nonatopic and atopic control subjects did not react to any purified allergens on the skin prick test. CONCLUSIONS: These results indicate that Ole e 1 and Ole e 2 are major allergens in patients with O. europaea pollinosis in our population. A combination of a few olive pollen allergens can substitute the crude extract for in vivo as well as in vitro diagnostic purposes.

An allergen from Olea europaea pollen (Ole e 7) is associated with plant-derived food anaphylaxis.

BACKGROUND: Several cross-reacting proteins have been identified as responsible of the co-occurrence of pollinosis and plant-derived food allergy. This association has been mainly described in the birch-apple syndrome but other pollens such as Olea europaea and other fruits may also contain homologous proteins. OBJECTIVE: To evaluate the associations between sensitization to allergens of Olea europaea pollen and confirmed plant-derived food allergy, in addition to investigate if any pattern of clinical hypersensitivity of food allergy reaction (oral allergy syndrome (OAS) or anaphylaxis) and/or any fresh fruit or nut allergy, are associated to one or several Olea pollen allergen(s). METHODS: One-hundred and thirty-four consecutive patients diagnosed with pollinosis by Olea were studied. Of these patients only 40, reported adverse reaction to plant-derived food. Twenty-one (group A) were classified as OAS and 19 (group B) as anaphylaxis. Skin-tests with six Olea pollen allergens and several groups of fruits, were performed. Double-blind placebo-controlled food challenge (DBPCFC), confirmed the diagnostics of food allergy with the exception of patients who suffered previous anaphylactic reaction. RESULTS: All patients, showed a positive skin prick test (SPT), against one or more of Olea europaea allergens. Sensitization to Ole e 7, was more frequent (P = 0.02) in patients from group B. A total of 84 DBPCFC were performed with 44% positive results. Challenge confirmed at least the 50% of positive SPT in any case (peach: 68.42%; pear: 50%; melon: 71.42% and kiwi: 53.84%). In patients from group B, significant association with O. europaea pollen allergens were found between positive SPT to Rosaceae fruits and Ole e 3 (P = 0.045) and Ole e 7 (P = 0.03); Cucurbitaceae and Ole e 7 (P = 0.03) and Actinidiaceae with Ole e 3 (P = 0.04). CONCLUSIONS: The results of this study, establish a new spectrum of associations between pollens and plant-derived foods: sensitization to olive profilin (Ole e 2) is not more frequent in OAS patients. Patients with anaphylactic reaction after eating fruit are also sensitized to Ole e 7, a LTP present in Olea pollen, and suffer pollinic symptoms. Finally a polcalcin (Ole e 3) could be also associated to Olea pollen respiratory and food allergy.

Immunotherapy with an extract of Olea europaea quantified in mass units. Evaluation of the safety and efficacy after one year of treatment.

Sensitization to olive pollen is a frequent cause of rhinoconjunctivitis (RC) and bronchial asthma (BA) in the region of Jaén (southern Spain), where this allergen reaches atmospheric levels of almost 7000 grains/m3 during pollen season (May and June) and produces high morbidity. Specific immunotherapy (SIT) has proven very efficient in allergic RC and BA caused by grass pollen. Considering the availability of a biologically standardized extract of Olea europaea, with its major allergen quantified in mass units, we decided to investigate SIT with this extract in a group of rhinitic and/or asthmatic patients monosensitized to olive. We studied tolerance, safety, and efficacy by comparison of the active group (subjected to SIT) with a control group that did not receive SIT. A hyposensitizing dose of Olea europaea extract was administered preseasonally, establishing a maintenance dose 3.8 times higher than those administered in conventional treatments. Eighty-three percent of the patients reached the proposed maximal dose of 75 BU, equivalent to 45 micrograms Ole e 1, with a rate of 0.8% of systemic reactions. A significant decrease in cutaneous (p < 0.001) and bronchial (p < 0.001) reactivity was observed in the active group, but not in the control group. Also, a decrease in specific IgE and an increase in IgG1 and IgG4 were found in the group of patients treated with SIT. Regarding clinical evolution, the active group, but not the control group, experienced a clear statistically significant improvement both in nasal (p < 0.05) and bronchial (p < 0.05) symptoms, in addition to a significant decrease in the consumption of antihistamines (p < 0.05) and beta 2-agonists (p < 0.01). In conclusion, SIT with olive extract proved to be safe and efficacious for the treatment of asthma and rhinitis caused by this allergen.

Estudio clínico de 32 pacientes con reacciones inducidas por diclofenaco / Diclofenac-induced reactions: a clinical study of 32 patients

Fundamento: La provocación oral controlada con diclofenaco induce reacciones cutáneas y respiratorias en pacientes con reacciones a otros AINEs. El objetivo de este estudio es describir las manifestaciones clínicas de las provocaciones orales controladas con diclofenaco en 32 pacientes con reacciones inducidas por AINEs. Pacientes y Métodos: Se estudiaron 32 pacientes con historia sugestiva de reacciones inducidas por AINEs. Todos los pacientes fueron incluidos en un protocolo de provocación oral controlada simple ciego con placebo con AINEs (paracetamol, isonixina, salsalato, piroxicam, diclofenaco y aspirina). Una historia sugestiva de reacción anafilactoide por diclofenaco contraindicó el uso de este fármaco durante la provocación. Resultados: Veinticinco pacientes presentaron una respuesta positiva con diclofenaco. En 22 pacientes (68 por ciento) se observaron reacciones cutáneas (angioedema o urticaria) y en 3 (9 por ciento) se objetivaron recciones de tipo respiratorio (nasooculares y asmáticas). La mayoría (98 por ciento) de las reacciones cutáneas y todos los pacientes con reacciones respiratorias presentaron reactividad cruzada con otros AINEs no implicados en la reacción previa. En los 7 pacientes restantes con reacción anafilactoide (23 por ciento) por diclofenaco se comprobó la tolerancia al resto de AINEs incluidos en el protocolo de provocación. Conclusiones: En nuestra población los pacientes con reacciones inducidas por diclofenaco son un grupo clínicamente heterogéneo, que puede ser clasificado de acuerdo con el síndrome clínico asociado a la reacción y el patrón de reactividad cruzada con otros AINEs (AU)

Immunological activity of recombinant Ole e 1 in patients with Olea europaea pollinosis.

BACKGROUND: Recombinant allergens have potential advantages over conventional allergenic extracts. However, these recombinant allergens should be evaluated for their antigenic activity and compared with their natural counterparts before being used for clinical purposes. METHODS: We studied 33 patients with seasonal rhinitis and/or bronchial asthma and a positive skin prick test to Olea europaea pollen extract, 10 atopic patients with no history of pollinosis and a negative skin prick test to O. europaea extract and 10 healthy controls. Skin prick tests and determination by ELISA of specific IgE to natural Ole e 1 (nOle e 1) and recombinant Ole e 1 (rOle e 1) expressed in Pichia pastoris were performed in all patients and controls. Inhibition assays were performed between nOle e 1 and rOle e 1 by ELISA. RESULTS: All patients with O. europaea pollinosis had positive skin test responses to both commercial O. europaea extract and nOle e 1 allergen, and all reacted to rOle e 1 on the skin prick test. The nonatopic and atopic control subjects with negative olive pollen skin test results did not react to rOle e 1 on the skin prick test, even at the highest concentrations, confirming the specificity of this test. We found a weak correlation between the wheal surface area produced by the prick test with nOle e 1 and the wheal surface area produced by rOle e 1 at 10 microgram/ml (r = 0.42, p < 0.05). Comparison of specific IgE against both nOle e 1 and rOle e 1 in the patients did not reveal any significant difference. There was a strong correlation between the amount of specific IgE against nOle e 1 and rOle e 1 (r = 0.99, p < 0.01). The two proteins displayed the same extent of binding inhibition to IgE antibodies in ELISA inhibition experiments. CONCLUSIONS: These results confirm the immunological activity of rOle e 1 expressed in P. pastoris and indicate that Ole e 1 is one of the major allergens in O. europaea pollinosis as evaluated by skin prick test and serological methods. The correlation between rOle e 1 and nOle e 1 in skin test results and serologic data indicates the potential of recombinant allergens for clinical applications and diagnosis of O. europaea pollen allergy.

Sensitization to Olea europaea: geographical differences and discrepancies.

Thirty eight patients from two geographical areas of Spain, with great differences in Olea europaea pollen counts were studied to investigate their in vivo and in vitro immune response to this pollen as a consequence of their different environmental allergen exposure. They were distributed in two groups (13 from Madrid, and 25 from Jaén). Skin sensitivity was assessed by a prick-test dose-response bioassay using serial dilutions of a biologically standardized allergen extract of O. europaea. Serological immune response was evaluated measuring specific antibody levels (IgE, IgG, IgG1 and IgG4). The patients from Jaén, who have a higher exposure to olive pollen, had higher levels of specific antibodies but significantly smaller wheal sizes than a similar patient population form the Madrid area, where olive pollen is not so copious. There is a great discrepancy between the results of skin prick tests (low cutaneous reactivity associated with high allergenic environmental load) and the levels of specific IgE to the olive pollen. While the level of specific antibodies increases with the allergenic load, the capacity to release mediators seems to be decreased, at least in the skin. Further studies are needed to evaluate if these findings also occur in other target organs with appropriate challenge tests (conjunctival, nasal and bronchial). This pattern should be studied with other allergens in large patient populations.

Allergy to natural honeys and camomile tea.

Precipitation of food allergy reactions is well known in some patients with pollinosis when they consume natural food, such as honey or camomile tea. We present 9 patients with hay fever, with or without asthma, who experienced systemic allergic reactions after ingestion of natural honeys from two local areas (Andujar and Granada) and/or camomile tea. Pollen analysis showed a high level in sunflower pollen (23.6% of pollen grains) in the honey from Andujar but not in that from Granada. The diagnosis of food and respiratory allergy was based on history, skin prick tests and specific IgE activity against pollen from Compositae. Conjunctival challenge with camomile extract also gave positive results. The above allergological tests and the inhibition studies carried out, suggest that pollen of Compositae may be responsible for allergic reactions to certain natural foods and that the reactions are mediated by an IgE-related mechanism.

Hypersensitivity to ketoconazole.

We report a patient who experienced generalized urticaria and facial angioedema following oral administration of ketoconazole. Skin prick tests with ketoconazole and oral challenge were positive. Conjugates of ketoconazole with human serum albumin were used for the in vitro study, obtaining a positive result in the histamine release test. No significant levels of IgE antibodies to ketoconazole were found by RAST. Controls did not react to any of these tests. These results suggest that the patient developed a type I hypersensitivity reaction to ketoconazole. In this case, skin prick tests with ketoconazole and histamine release test with a conjugate of ketoconazole with human serum albumin were useful in ketoconazole hypersensitivity diagnosis. Finally, skin tests with other imidazole agents were carried out, including metronidazole, ornidazole, and fluconazole that were negative.

Anaphylactic shock by rupture of hydatid hepatic cyst. Follow-up by specific IgE serum antibodies.

Total and specific serum IgE antibodies were estimated in a 68-year-old woman with anaphylactic shock due to spontaneous rupture of hydatid cyst of the liver. After she had recovered, an abdominal ultrasonography showed a cyst, 10 x 15 cm, in the right hepatic lobe. The cyst was surgically removed. Antihydatid IgE in the acute phase and periodically after surgical intervention, determined by Phadezym RAST, Pharmacia, and Pharmacia CAP system (a new solid-phase immunoassay, fully automated, for the titration of specific IgE with greater sensitivity in the detection of low IgE antibody levels), showed decreasing antihydatid IgE antibodies on day 10 after surgical intervention and may thus serve to monitor the evolution of hydatid disease.