Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units.

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results.

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting β2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-γ], and tumor necrosis factor [TNF-α]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-γ, and TNF-α (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results (AU)

Se ha llevado a cabo un estudio prospectivo y multicéntrico con el objetivo de valorar la tolerancia y posible efecto a corto plazo de las vacunas alergénicas administradas bajo pauta cluster en los meses inmediatamente anteriores al inicio de la estación polínica. El estudio se realizó en 8 centros, incluyéndose un total de 191 pacientes (niños y adultos) con enfermedad alérgica respiratoria por sensibilización a polen de olivo y/o gramíneas. De ellos, 34 actuaron como controles y a los pacientes restantes se les administró inmunoterapia bajo una pauta cluster, en la fase de iniciación, de 8 dosis administradas en 4 visitas. Tras 3 meses de tratamiento, se registraron diferencias significativas entre ambos grupos en el consumo de medicación (antihistamínicos en colirio y orales -p = 0,045 y p = 0,001 respectivamente- y ß2 de corta duración -p = 0,004-) así como en síntomas pulmonares (sibilancias y tos -p = 0,035 y 0,014 respectivamente-). Por otro lado, se determinó el perfil de citocinas (IL-4, 5, 10 y 2, IFN-gamma y TNF-a) de forma previa al inicio del tratamiento y al finalizar el seguimiento (4-5 meses). Se observaron descensos en los niveles de IL-4, 5 y 10 (perfil TH2) y aumento en los valores de IL-2, IFN-gamma y TNF-a (perfil TH1), más marcados en el grupo activo que en el control, sin alcanzar significación estadística. No se registraron efectos adversos severos. Por tanto, podemos observar que la pauta ensayada mostró un adecuado perfil de tolerancia, y tras pocos meses de tratamiento se registraron cambios significativos en la puntuación de síntomas y medicación, siendo necesaria la realización de un estudio con un diseño doble ciego frente a placebo para confirmar los resultados obtenidos (AU)

Reacción adversa a isonixina con Buena tolerancia a otros AINE / Selective adverse reaction to Isonixine with good tolerance to other NSAIDs

Introducción: Los derivados del ácido antranílico son un grupo de antinflamatorios no esteroideos entre los que se encuentran isonixina, ácido mefenámico y ácido meclofenámico. Caso clínico: Presentamos el caso de un varón de 19 años de edad que presentó un cuadro de urticaria, angioedema facial y disnea tras tomar la primera dosis de isonixina (Nixyn®) y de amoxicilina-clavulánico (Augmentine®) por una infección dental. Precisó tratamiento en el servicio de urgencias con salbutamol y corticoides por vía parentera1 que hicieron desaparecer el cuadro. Se descartó alergia a amoxicilina-clavulánico mediante pruebas cutáneas, determinación de IgE específica y prueba de tolerancia oral. Se realizaron pruebas cutáneas con isonixina, ácido mefenámico y ácido meclofenámico que fueron negativas. La provocación oral con isonixina fue positiva tras administrar 100 mg. El paciente toleró in problemas dosis terapéuticas de ácido mefenámico, ácido meclofenámico y Aspirina®. Discusión: Éste es el primer caso de un paciente con una reacción adversa inmediata selectiva a isonixina que toleraba otros derivado del ácido antranílico y Aspirina® (AU)

Background: The anthranylic acid derivatives represent a non-steroidal anti-inflammatory drug (NSAID) group that includes isonixine and the mefenamic and meclofenamic acid salts. Case report: We report the case of a 19-year-old male who developed urticaria facial angioedema and dyspnoea after the ingestion of the first dose of Isonixine (Nixyn®) and Amoxycillin – Clavulanate (Augmentine®) because of an odontological infection. The patient required emergency management at the Outpatient emergency Ward with parenteral salbutamol and corticosteroid, leading to full remission of the clinical picture. Allergic intolerance to the amoxycillin - clavulanate association was ruled out through kin test, specific lgE quantitation and oral challenge test. Skin tests were also performed with isonixine, mefenarnic acid and meclofenarnic acid, with negative results. The oral challenged test with isonixine was positive after the administration of a 100-mg dose. The patient tolerated with no untoward problem the administration of therapeutic doses of mefenamic, meclofenamic and acetylsalicylic acids. Discussion: This is to our knowledge the first reported case of immediate selective adverse reaction to isonixine with tolerance to other anthranylic acid derivatives and to acetylsalicylic acid (AU)

Occupational asthma from natural rubber latex. Specific inhalation challenge test and evolution.

BACKGROUND: Natural rubber latex (NRL) is the most frequent cause of occupational respiratory problems in hospital workers. OBJECTIVE: To describe the diagnostic methodology, including the specific inhalation challenge (SIC), used on patients diagnosed as having occupational asthma due to NRL in our Allergy Department during a 6-year period from 1989 to 1995. METHODS: In 19 patients diagnosed as having occupational asthma due to NRL, clinical severity was assessed with a combined score for symptoms and medication use. Skin prick tests with aeroallergens, latex, papain, kiwi and chestnut, total IgE, serum-specific latex IgE, respiratory function study, methacholine test, specific conjunctival test, and SIC test with latex were done. RESULTS: All but three patients worked in hospitals. All presented urticaria and rhinoconjunctivitis, and six also suffered anaphylaxis, usually preceded by asthma. Clinical fruit allergy was present in eight patients. The latency period was variable (0.25-27 years). The intensity of symptoms was low to moderate. Specific IgE, skin prick, and conjunctival tests to latex were positive in all cases. SICs were done in 12 patients. All of them presented isolated immediate reactions. No adverse reactions were observed. Duration of follow-up ranged from 1 to 7 years. Twenty-six percent of the patients kept their job, 26% changed jobs but remained in health care, and 48% switched to jobs unrelated to health care. Only 16% were free of symptoms without treatment, while 32% needed bronchodilators and 52% needed inhaled steroids. The specific bronchial challenge test was safe, but it did not predict the course of the illness. Duration of exposure and intensity of symptoms did correlate with prognosis, however. CONCLUSIONS: NRL acts as a common aerollergen. Minor symptoms often precede occupational asthma. The SIC test was safe in the hands of trained technicians. Occupational asthma due to NRL seems to have a poor prognosis.

[Asthma and allergy due to carmine dye]. / Asma y alergia por el colorante carmín.

Cochineal carmine, or simply carmine (E120), is a red colouring that is obtained from the dried bodies of the female insect Dactylopius coccus Costa (the cochineal insect). We have evaluated the prevalence of sensitization and asthma caused by carmine in a factory using natural colouring, following the diagnosis of two workers with occupational asthma. The accumulated incidence of sensitization and occupational asthma due to carmine in this factory are 48.1% and 18.5% respectively, figures that make the introduction of preventive measures obligatory. Occupational asthma caused by inhaling carmine should be considered as a further example of the capacity of certain protein particles of arthropods (in this case cochineal insects) to act as aeroallergens. Carmine should be added to the list of agents capable of producing occupational asthma, whose mechanism, according to our studies, would be immunological mediated by IgE antibodies in the face of diverse allergens of high molecular weight, which can vary from patient to patient. Nonetheless, given the existence of different components in carmine, it cannot be ruled out that substances of low molecular weight, such as carminic acid, might act as haptenes. Besides, since we are dealing with a colouring that is widely used as a food additive, as a pharmaceutical excipient and in the composition of numerous cosmetics, it is not surprising that allergic reactions can appear both through ingestion and through direct cutaneous contact. We find ourselves facing a new example of an allergen that can act through both inhalation and digestion, giving rise to an allergolical syndrome that can show itself clinically with expressions of both respiratory allergy and alimentary allergy.

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.

Asma y alergia por el colorante carmín / Asthma and allergy due to carmine dye

El carmín de cochinilla o simplemente carmín (E120) es un colorante rojo que se obtiene de las hembras desecadas del insecto Dactylopius coccus Costa (cochinilla).Hemos evaluado la prevalencia de sensibilización y asma por carmín en una fábrica de colorantes naturales tras diagnosticar dos de sus trabajadores de asma ocupacional. La incidencia acumulada de sensibilización y asma ocupacional por carmín en nuestra fábrica es de 48,1 por ciento y 18,5 por ciento respectivamente, datos que obligan a implantar medidas de prevención. El asma ocupacional causado por inhalación de carmín debe considerarse como un ejemplo más de la capacidad que tienen ciertas partículas proteicas de artrópodos (en este caso las cochinillas) de actuar como aeroalergenos . El carmín debe añadirse a la lista de agentes capaces de producir asma ocupacional, cuyo mecanismo, según nuestros estudios, sería inmunológico mediado por anticuerpos IgE frente a diversos alergenos de alto peso molecular, que pueden variar de un paciente a otro. No obstante, dada la existencia de diferentes componentes en el carmín, no puede descartarse la posibilidad de que sustancias de bajo peso molecular, como el ácido carmínico, puedan actuar como haptenos. Además, al tratarse de un colorante ampliamente utilizado como aditivo alimentario, como excipiente farmacéutico y en la composición de numerosos cosméticos, no es de extrañar que puedan aparecer reacciones alérgicas tanto por su ingestión como por el contacto cutáneo directo. Nos encontramos, ante un nuevo ejemplo de un alergeno que puede actuar tanto por vía inhalatoria como digestiva, dando lugar a un síndrome alergológico que puede presentarse clínicamente con manifestaciones tanto de alergia respiratoria como alimentaria (AU)

Identification of allergens involved in occupational asthma due to carmine dye.

BACKGROUND: Carmine has been implicated as an etiologic agent of occupational asthma, but the allergens involved have not been yet identified. OBJECTIVE: To identify the allergens involved in occupational asthma due to carmine dye. METHODS: An in vitro study based in SDS-PAGE and IgE immunoblotting with carmine and cochineal extracts was performed. Sera from three carmine dye workers diagnosed with occupational asthma induced by carmine dye and from seven nonatopic subjects were used. RESULTS: Three proteins of around 30, 28, and 17 kD in raw cochineal extract and another protein of 50 kD in the boiled one were demonstrated by SDS-PAGE. Two proteins of around 50 and 28 kD were observed in the carmine extract by the same technique. Specific IgE binding bands at 17 kD in cochineal raw extract, at 50 kD in the boiled one, and at 28 kD in carmine extract were demonstrated by IgE immunoblotting. CONCLUSIONS: We have identified three allergens of around 17, 28, and 50 kD implicated in occupational asthma of three carmine workers.

Effect of current exposure to Der p 1 on asthma symptoms, airway inflammation, and bronchial hyperresponsiveness in mite-allergic asthmatics.

The existence of a dose-response relationship between indoor allergen exposure and sensitization has been widely described, but the effect of allergen exposure on asthma activity (symptoms, bronchial hyperresponsiveness [BHR], and inflammation) is not clear. Our aim was to determine the existence of an association among current exposure to mite allergens and symptoms, BHR, and airway inflammation assessed in blood and sputum from asthmatic patients sensitized to Dermatophagoides pteronyssinus. We selected 31 mild and recently diagnosed (12-24 months) asthma patients sensitized to D. pteronyssinus. Allergenic exposure (Der p 1, Der 2) was assessed by a commercial assay based on monoclonal antibodies (mAb), carried out on the dust samples collected from patients' beds in a standardized way. Patients completed an asthma symptom questionnaire and underwent skin tests, methacholine bronchial challenge, and sputum induction. Sputum cell profile was analyzed and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin(IL)-5 levels were quantified in sputum supernatant. Total eosinophil numbers and ECP levels were measured in blood samples. Most patients were exposed to Der p 1 levels under 2 microg/g of dust. Der p 1 exposure was higher among the subjects with positive sputum tryptase detection (P = 0.020). Der p 1 levels showed a trend toward correlation with asthma symptoms (P = 0.066, r = 0.36) and correlated with sputum tryptase levels (P = 0.032, r = 0.42). No relationship between BHR, eosinophilic inflammation, and allergenic exposure was found. Our results suggest that asthma symptoms and lung mast-cell activation are at least partially dependent on current allergen exposure. The lack of correlation between mite exposure, eosinophilic inflammation, and BHR supports the role of other factors that enhance the immunologic response initiated by allergen, increasing the activity of asthma.

Dermatophagoides pteronyssinus cluster immunotherapy. A controlled trial of safety and clinical efficacy.

We designed a cluster schedule of immunotherapy for patients allergic to Dermatophagoides pteronyssinus to reach the maximal recommended dose in 7 weeks. We compared its safety and clinical efficacy with those of a conventional schedule in a controlled trial. Sixty-three patients were randomized as follows: 29 were treated with the cluster schedule, 15 with a conventional schedule and 19 without immunotherapy. A standardized extract was used. Clinical efficacy was measured by visual analog scale, clinical severity score, symptom/medication diary cards and control of peak expiratory flow (PEF) in asthmatic patients, before immunotherapy (T0), on reaching the maintenance phase (T1), and after 6 (T2), 12 (T3) and 18 months of maintenance (T4). The safety of immunotherapy was found to be good. Visual analog scale improved significantly at T4 in the cluster and conventional schedules, and clinical severity score also improved from T1 in these schedules. Diary cards improved from T1 in the cluster schedule and from T2 in the conventional schedule in asthmatic patients. Significant improvements in diary cards in rhinitis patients and PEF were found only in the cluster schedule. There were no changes in the group without immunotherapy. In conclusion, our cluster schedule showed as good tolerance and clinical efficacy as the conventional schedule in patients allergic to D. pteronyssinus. These clinical improvements did not appear in the group without immunotherapy.

Occupational asthma and food allergy due to carmine.

Carmine (E120), a natural red dye extracted from the dried females of the insect Dactylopius coccus var. Costa (cochineal), has been reported to cause hypersensitivity reactions. We report a case of occupational asthma and food allergy due to carmine in a worker not engaged in dye manufacturing. A 35-year-old nonatopic man, who had worked for 4 years in a spice warehouse, reported asthma and rhinoconjunctivitis for 5 months, related to carmine handling in his work. Two weeks before the visit, he reported one similar episode after the ingestion of a red-colored sweet containing carmine. Peak flow showed drops higher than 25% related to carmine exposure. Prick tests with the cochineal insect and carmine were positive, but negative to common aeroallergens, several mites, foods, and spices. The methacholine test was positive. Specific bronchial challenge test with a cochineal extract was positive with a dual pattern (20% and 24% fall in FEV1). Double-blind oral challenge with E120 was positive. The patient's sera contained specific IgE for various high-molecular-weight proteins from the cochineal extract, as shown by immunoblotting. Carmine proteins can induce IgE-mediated food allergy and occupational asthma in workers using products where its presence could be easily overlooked, as well as in dye manufacture workers.

Occupational allergic contact dermatitis due to airborne spiramycin.

We report the case of a man who worked in a feed factory. He developed allergic contact dermatitis due to airborne spiramycin, a commonly used antibiotic in veterinary medicine. The patient suffered recurrent outbreaks of eczematous lesions on uncovered areas during working periods. Diagnosis was made based on history, positive patch tests to spiramycin and to some feed compounds containing spiramycin, and on disappearance of lesions on leaving the work place.

Reactive airways dysfunction syndrome: two case reports.

Reactive airways dysfunction syndrome (RADS) is a type of asthma that develops in subjects without prior pulmonary disease, following single or multiple exposure to high levels of nonimmunogenic irritants. The main difference from classic occupational asthma is the absence of a latency period. Non-specific bronchial hyperresponsiveness is characteristic of the disease and usually persists after cessation of exposure. We report the cases of two subjects in whom RADS developed after occupational exposure to irritants.

[Sweet's syndrome. Presentation of six cases and review of the literature]. / Síndrome de Sweet. Presentacíon de 6 casos y revisión de literatura.

The acute febrile neutrophilic dermatosis or Sweet syndrome, initially described in 1964 by Robert Sweet (1). It is characterized fever, neutrophilic leucocytosis, abrupt appearance of erythematous, painful, cutaneous plaquets and dense dermal infiltrate consisting of mature neutrophils without vasculitis sings. Malignancy has been described in the 10-15% of the reported cases. We report our series of 6 patients diagnosticated of this illness in our department. One of this patients has Sweet syndrome associated with a malignancy disorder. All of them had diagnostic criteria of the described disease and had good response to corticotherapy. We also report a bibliographic review of this infrequent syndrome.

Indoor allergens and dwelling characteristics in two cities in Spain.

BACKGROUND: Indoor allergens are common causes of sensitization and asthma. Climatic and home conditions can modify their levels. OBJECTIVE: We studied the influence of climatic conditions and home characteristics on the exposure to indoor allergens of mite allergic asthmatic subjects in two Spanish cities with different climates (Las Palmas and Pamplona). METHODS: We included 65 subjects diagnosed with asthma caused by Dermatophagoides pteronyssinus. A questionnaire about their dwellings was completed. Home dust samples were collected. Mite (Der p1, Der f1, Der 2) and cat (Fel d1) allergens were measured by a monoclonal-antibodies based ELISA. RESULTS: Characteristics of dwellings were similar in both areas. Der p1 was the main allergen (0-44 micrograms/g). Der p1, Der f1 and Der 2 levels were higher in the homes in Las Palmas (p < 0.001, p < 0.01 and p < 0.001, respectively). Damp homes in Pamplona had higher Der p1 levels, similar to those detected in homes in Las Palmas. Fel d1 levels (0-78.90 micrograms/g) were only related to the presence of cats in the dwelling (p < 0.001). CONCLUSIONS: D. pteronyssinus allergen exposure was influenced by climatic conditions and dampness in homes in temperate regions. Humidity in homes can generate an ideal environment for mite growth despite unfavorable outdoor climatic conditions. Fel d1 levels were only related to the presence of a cat in the house.

Anaphylaxis from cow's milk casein.

The case of a 35-year-old woman who suffered anaphylaxis after the ingestion of milk or milk-containing products is presented. Symptoms also appeared after the patient used a cosmetic which contained casein. Skin prick tests, specific IgE measurement, and immunoblotting were carried out with cow's milk extract, and its purified proteins: casein, beta-lactoglobulin, and alpha-lactalbumin. Specific IgE to cow's milk casein was detected with the three tests. Immunoblotting revealed one band of 24 kDa approximately corresponding to the beta-fraction of casein. Negative results to beta-lactoglobulin and alpha-lactalbumin were obtained with the three methods. Symptoms were controlled by rigorous dietary and behavior measures.