Itraconazole, an effective adjunctive treatment for allergic bronchopulmonary aspergillosis.

We report the case of a 21-year old man with a long-standing history of severe asthma and allergic rhinosinusitis who developed progressive worsening of dyspnea, wheezing, productive cough, and nasal obstruction, with little response to antibiotics and repeated short courses of oral corticosteroids. A diagnosis of allergic bronchopulmonary aspergillosis was made on the basis of a combination of clinical, laboratory and radiographic findings.Treatment with oral methylprednisolone and itraconazole resulted in an improvement in symptoms, lung function and computed tomography results, as well as in a decrease in total serum immunoglobulin E. This case report highlights the importance of a high degree of clinical suspicion in order to diagnose and treat allergic bronchopulmonary aspergillosis in patients with a long-standing history of severe asthma as early as possible as this has a major impact on prognosis. It also highlights the effectiveness of itraconazole as adjunctive therapy to systemic corticosteroids in this condition.

Thoracic high resolution computed tomography (HRCT) in asthma.

INTRODUCTION: High-resolution computed tomography (HRCT) is a widespread medical imaging method for the study of thoracic diseases. In asthma it is very useful particularly when it is difficult to achieve an effective control of disease, and in severe deterioration. AIM: It was intended to evaluate the imaging changes by HRCT in asthmatic patients and to assess the expression according to the symptoms and duration of disease. MATERIAL AND METHODS: Thirty three patients from the Outpatient Department, with asthma classified in the different clinical severity stages according to GINA, were randomly included. They were submitted to HRCT (Somaton Plus-4, Siemens). The lesions were classified in reversible (mucoid impaction, acinar pattern centrilobular nodules and lobar collapse) and irreversible (bronchiectasis, bronchial wall-thickening, sequellar line shadows and emphysema). RESULTS: The 33 asthmatic patients (20 female) had an average age of 44.76 +/- 16.98 years and a mean disease evolution time of 23.39 +/-14.83 years. 30% had mild persistent asthma, 43% moderate persistent asthma and 27% severe persistent asthma. All the patients were under inhaled corticotherapy. Only 6 patients had normal HRCT 4 with mild persistent asthma (4 to 25 years of duration of disease) and 2 with moderate persistent (10 to 48 years of duration of disease). 81.81% of the patients had changes in HRCT, being the irreversible lesions the most frequent. The most important irreversible lesions were observed in severe asthma patients with longer duration of disease. All the patients with reversible lesions had also irreversible changes. Most of the bronchiectasis were centrally located and were found in severe asthma patients. Irreversible changes were identified in 3 patients with mild asthma and a maximum of 6 years of duration of disease. DISCUSSION: HRCT findings were related with asthma severity and long lasting disease but there are some asthmatics that also present early abnormalities, even in milder forms. All the groups of asthmatic patients presented all types of imaging changes, including the irreversible ones. In asthma these changes can be the result of individual patterns of response to frequent exacerbations, leading to a persistent chronic inflammatory process that will determine airway remodelling, even in early stages of disease and/or mild asthma.

Body mass index and airway hyper-responsiveness in individuals without respiratory disease.

BACKGROUND: Overweight and obesity are major health issues in Western societies. They are related with a higher risk of different co-morbidities but their relationship with airway hyperresponsiveness (AHR) is still under discussion. Nevertheless, they are related to higher severity in asthma and other respiratory diseases. The aim of the study was to analyze the AHR in individuals with normal lung function without respiratory disorders, according to body mass index (BMI) calculation. METHODS: We performed clinical observation and basal lung function tests (LFT) in 595 consecutive individuals in order to exclude respiratory disease. 377 individuals fulfilled the criteria of normal values according international guidelines. They were submitted to standardized treadmill exercise test followed by bronchodilator test. FVC, FEV1, FEF 25/75, RV and Raw were obtained at different conditions according to BMI groups (I: lean; II: normal; III: overweight; IV obese). RESULTS: 55.2% of the sample was overweight or obese, and a signficant relationship was found with female gender and older ages (p=0.0046 and p<0.0001 respectively). The positive response to exercise test or bronchodilator beta2 agonists was not significantly frequent compared with the other groups. In obese individuals the exercise markedly reduced basal Raw and increased FEF 25/75. Lean individuals showed higher basal values of RV that was reduced upon exercise. Response to 12 agonists showed no differences according to weight biotypes. CONCLUSION: BMI hampers lung function in normal individuals, and seems not to be related to AHR. Regular exercise should be encouraged in overweight and obese individuals, since it increases their bronchial permeability as shown in lower frequency of positive exercise tests. The same is advisable for lean individuals for different reasons. Their increased basal RV and Raw improve upon exercise. Despite overweight and obesity are being related to a low-grade of basal systemic inflammation, there was no association with a higher basal bronchial hyperresponsiveness in these individuals.

Goat's milk allergy.

BACKGROUND: Goat's milk (GM) allergy not associated with allergy to cow's milk (CM) is a rare disorder. Caseins have been implicated has the major allergens eliciting symptoms. METHODS: We report the case of a 27 years-old female patient that experienced two episodes of urticaria related to ingestion of goat's cheese (GC). She tolerated CM, dairy products and sheep cheese. Skin prick tests were performed with GM, CM, bovine casein and alpha -lactalbumin and fresh milk and GC. Serum specific IgE to GM, CM and its fractions, and GM and CM immunobloting assays with inhibition were also evaluated. RESULTS: Skin tests were positive to GM and GC and negative to CM. GM immunoblot showed an IgE-binding 14 kDa band that was totally inhibited after serum pre-incubation with GM. CONCLUSIONS: Allergens other than casein can be involved in allergy to GM. Even small quantities of protein can elicit symptoms.

Goat's milk allergy / Alergia a leche de cabra

Background: Goat's milk (GM) allergy not associated with allergy to cow's milk (CM) is a rare disorder. Caseins have been implicated has the major allergens eliciting symptoms. Methods: We report the case of a 27 years-old female patient that experienced two episodes of urticaria related to ingestion of goat's cheese (GC). She tolerated CM, dairy products and sheep cheese. Skin prick tests were performed with GM, CM, bovine casein and a -lactalbumin and fresh milk and GC. Serum specific IgE to GM, CM and its fractions, and GM and CM immunobloting assays with inhibition were also evaluated. Results: Skin tests were positive to GM and GC and negative to CM. GM immunoblot showed an IgE-binding 14 kDa band that was totally inhibited after serum pre-incubation with GM. Conclusions: Allergens other than casein can be involved in allergy to GM. Even small quantities of protein can elicit symptoms

Introducción: La alergia a leche de cabra sin asociación a alergia a leche de vaca es una situación muy poco frecuente. Del conjunto de alergenos mayores, las caseínas son las más involucradas en los síntomas. Métodos: Se presenta lo caso de una paciente de 27 anos de edad, que describe desde hace 3 años dos episodios de urticaria tras ingestión de queso de cabra. Tolera leche de vaca y oveja, así como sus derivados. Se realizaron pruebas cutáneas (prick) con leche de cabra (LC), leche de vaca (LV), caseína y a-lactoalbumina bovinas y también con leche fresca y queso de cabra. Adicionalmente se procedió a determinación de los niveles de IgE sérica especifica a LC, LV y fracciones así como ensayos de immunobloting de LC y LV con inhibición. Resultados: Las pruebas cutáneas fueran positivas a leche y queso de cabra y negativas a LV. El immunoblot con LC demostró una banda de 14 kDa de ligación a IgE, que ha sido totalmente inhibida tras la incubación previa con LC. Conclusiones: Otros alergenos además de caseína pueden estar involucrados en la alergia a LC. También pequeñas cantidades de proteína pueden desencadenar síntomas

Low-dose intravenous gammaglobulin in the treatment of severe autoimmune urticaria.

BACKGROUND: An autoimmune pathogenic mechanism is implicated in about one-third of patients with chronic urticaria (CU), involving circulating functional autoantibodies to either the high affinity IgE receptor (LgG1/IgG3 anti-FcARI) or to IgE, with histamine releasing activity. New therapeutic approaches had been developed for patients with severe or unresponsive to treatment symptoms, including the use of intravenous immunoglobulins (IVIG) as immunomodulators. AIM: To assess the efficacy of IVIG treatment in patients with evidence of autoimmune CU. METHODS: A group of 29 patients (F = 20, M = 9) with the diagnosis of autoimmune CU were selected from the outpatient department. All the patients showed daily symptoms of urticaria and/or angioedema, with unsatisfactory response to conventional therapy and a positive intradermal autologous serum test (AST). They were submitted to low dose of IVIG treatment each 4 weeks (0.15 g/kg), for a minimum of 6 months and a maximum of 51 months. They were evaluated for clinical scores, need of oral medication and AST results, before and after treatment. RESULTS: A clinical improvement was observed in 26 patients, with reduction of urticaria or angioedema complaints (p < 0.0001) and decreasing need for oral antihistamine medication (p = 0.002). 3 patients drop-out the treatment: one depending of severe adverse event and the other 2 with no response after the 5th treatment. 19:26 patients achieved complete remission of symptoms. A reduction of histamine-releasing activity was found in the majority of the patients, documented by the decrea, se of reactivity in AST at the end of the treatment (p = 0.002). 20 patients remained without symptoms during 12 months after. the active treatment, and the other 6 only reported non-severe complaints. CONCLUSION: IVIG is an effective therapeutic option in patients suffering from severe CU refractory to conventional treatment, in which autoimmune mechanism is involved. The efficacy persists for at least 12 months after treatment. However, the number of infusions needed to achieve clinical control, showed great range between patients.

Aeroallergens sensitization in an allergic paediatric population of Cova da Beira, Portugal.

Cova da Beira is an interior central region of Portugal, with a population of 93,000 inhabitants. The first pollen counts performed in Portugal revealed the highest values of the country in this area. The aim of this study was to assess the aeroallergens sensitization in an allergic population, according to the age groups. In a 5 year period (1995-2000) 1790 consecutive outpatients were observed for suspected allergic symptoms. We included in this study all the 557 paediatric (< or = 15 years old) observed patients (317 male (57%) and 240 female (43%) with an average age of 7.6 < or = 4.2 years old). They were divided in three age groups (Group I: < or = 5 yr; Group II: 6-10 yr; Group III: 11-15 yr). 371 patients were submitted to skin prick tests to aeroallergens. 86.5% of these patients were sensitised to at least one allergen extract. The most representative aeroallergens sensitization were grasses mixture (44.9%), D. pteronyssinus (32.5%), D. farinae (29.1%), Olea europea (27.5%), Parietaria judaica (23.4%), cat dander (16.1%), Artemisia vulgaris (17.6%), Robinia pseudoacacia (12.2%), Platanus acerifolia (11.4%), Tilia cordata (11.4%) moulds mixture (11.2%), Plantago lanceolata (10.6%), dog dander (10.4%), and Pinus radiata (7.5%). The sensitisation to indoor aeroallergens, was similar in all age groups and it was less important than that of pollens. The prevalence of sensitisation to grasses was the greatest in all ages and the house dust mites sensitization was the second most prevalent. The highest pollens counts in this region could explain the early sensitisation even in young children.

Aeroallergens sensitization in an allergic paediatric population of Cova da Beira, Portugal

Cova da Beira is an interior central region of Portugal, with a population of 93 000 inhabitants. The first pollen counts performed in Portugal revealed the highest values of the country in this area. The aim of this study was to assess the aeroallergens sensitization in an allergic population, according to the age groups. In a 5 year period (1995-2000) 1790 consecutive outpatients were observed for suspected allergic symptoms. We included in this study all the 557 paediatric (<= 15 years old) observed patients (317 male (57 %) and 240 female (43 %) with an average age of 7.6 <= 4.2 years old). They were divided in three age groups (Group I: <= 5yr; Group II: 6-10yr; Group III: 11-15yr). 371 patients were submitted to skin prick tests to aeroallergens. 86.5 % of these patients were sensitised to at least one allergen extract. The most representative aeroallergens sensitization were grasses mixture (44.9 %), D. pteronyssinus (32.5 %), D. farinae (29.1 %), Olea europea (27.5 %), Parietaria judaica (23.4 %), cat dander (16.1 %), Artemisia vulgaris (17.6 %), Robinia pseudoacacia (12.2 %), Platanus acerifolia (11.4 %), Tilia cordata (11.4 %) moulds mixture (11.2 %), Plantago lanceolata (10.6 %), dog dander (10.4 %), and Pinus radiata (7.5 %). The sensitisation to indoor aeroallergens, was similar in all age groups and it was less important than that of pollens. The prevalence of sensitisation to grasses was the greatest in all ages and the house dust mites sensitization was the second most prevalent. The highest pollens counts in this region could explain the early sensitisation even in young children

Cova da Beira es una región interior del centro de Portugal con una población de 93.000 habitantes. Los primeros recuentos de polen realizados en Portugal revelaron que en esta zona se hallan los valores más elevados del país. El objetivo del presente estudio fue evaluar la sensibilización a los aeroalérgenos en una población alérgica según los grupos de edad. En un período de 5 años (1995-2000) se observaron 1.790 pacientes ambulatorios consecutivos con posibles síntomas alérgicos. En el estudio incluimos a los 557 pacientes pediátricos (de <= 15 años) observados (317 niños (57 %) y 240 niñas (43 %), con una edad media de 7,6 <= 4,2 años). Se dividieron en tres grupos de edad (grupo I: <= 5 años; grupo II: 6-10 años; grupo III: 11-15 años). Se sometieron 371 pacientes a pruebas cutáneas con aeroalérgenos. El 86,5 % de los mismos estaban sensibilizados como mínimo a un extracto de alergeno. Los alérgenos más significativos frente a los que se observó sensibilización fueron: mezcla de hierbas (44,9 %), D. pteronyssinus (32,5 %), D. farinae (29,1 %), Olea europea (27,5 %), Parietaria judaica (23,4 %), caspa de gato (16,1 %), Artemisia vulgaris (17,6 %), Robinia pseudoacacia (12,2 %), Platanus acerifolia (11,4 %), Tilia cordata (11,4 %), mezcla de mohos (11,2 %), Plantago lanceolata (10,6 %), caspa de perro (10,4 %) y Pinus radiata (7,5 %). La sensibilización a los aeroalérgenos domésticos fue similar en todos los grupos de edad y menos importante que la de los pólenes. La prevalencia de la sensibilización a las hierbas fue la principal en todos los grupos de edad, siendo la segunda en prevalencia la sensibilización a los ácaros domésticos. Los elevados niveles de polen de la región podrían explicar la sensibilización precoz incluso en niños de muy corta edad

Development of new IgE specificities to hymenoptera allergens during venom-specific immunotherapy.

BACKGROUND: Despite the benefits of specific immunotherapy (SIT) being clinically well documented for allergic diseases, new IgE specificities to SIT extract allergens could be induced during the treatment. The authors evaluated these changes in patients allergic to Hymenoptera. METHODS: Six patients allergic to Hymenoptera venom were included in the study. Specific IgE (sIgE) levels determination and IgE immunoblots to Apis mellifera, Vespula spp. and Polistes spp. venom were performed before and after one year of SIT. RESULTS: All patients had sIgE levels reduction, after the first year of treatment, except one in whom there was an increase in sIgE levels to Apis mellifera venom, and two patients that maintained a similar value for Vespula spp. venom sIgE before and after one year of treatment. The immunoblot analysis revealed that most of the bands detected before beginning SIT, decreased in intensity or disappeared after one year of treatment. 3/6 patients developed new IgE specificities to venom extracts: one patient to the venom allergens in the treatment, other patient to allergens in other venom and another patient to both. After one year of treatment one of these patients tolerated a field sting by the corresponding insect. The newly recognised proteins were all minor allergens. CONCLUSION: These results confirm that sIgE levels tend to reduce during SIT, and the bands identifying some allergens in the blot tend to decrease or disappear. Nonetheless venom SIT can be responsible for the induction of new sensitisations to other venom allergens, apparently without clinical relevance.

Urban versus rural environment--any differences in aeroallergens sensitization in an allergic population of Cova da Beira, Portugal?

Cova da Beira is an interior central region of Portugal, with a population of 93000 inhabitants divided in urban and rural living areas. The aim of this study was to access the prevalence of aeroallergens sensitisation in an allergic population, according to the urban and the rural environmental exposure and according to age. 1096 patients observed for suspected allergic symptoms, for a five-year period (1995-2000) were submitted to skin prick tests and were included in this study. They were divided in two environmental exposure groups (A: urban; B: rural) and in to four age subgroups (subgroup I: < or = 10yr; subgroup II: 11-20yr; subgroup III: 21-40yr; subgroup IV: >40yr). The total population included 444 male (40.5%) and 652 female (59.4%) with an average age of 26.5 +/- 17.2 yr. 83% of the 1096 performed SPT were positive. The frequency of aeroallergens sensitisation, comparing the urban versus the rural environment, was respectively: D. pteronyssinus 32% and 34.7%, D. farinae 28.5% and 30.7%, moulds mixture 15.3% and 12%, cat dander 17.1% and 15.2%, dog dander 11% and 10%, grasses mixture 51.3% and 36.4%, Parietaria judaica 29.4% and 14%, Olea europea 30.2% and 23.3%. The sensitisation to indoor aeroallergens, was similar in all the age subgroups and it was lower than that to pollens. There were important differences concerning the pollen sensitisation, when comparing the urban and the rural environmental exposure. We admit that pollution could enhance the sensitisation to pollens in the urban environment.

Kinetics and dynamic evaluation of specific immunotherapy.

UNLABELLED: Specific immunotherapy (SIT) is frequently used in the treatment of allergic diseases. However, the mechanisms by which SIT achieves clinical improvement remained unclear. We decided to study the in vivo kinetics of this therapy, using a nuclear medicine approach (leukocytes labelled with 99mTc-HMPAO) in patients on maintenance doses of specific immunotherapy with confirmed clinical efficacy. MATERIAL AND METHODS: We studied 13 allergic patients grouped according to different treatment schedules: subcutaneous aqueous allergenic extract (3 latex and 2 hymenoptera venom), subcutaneous depot extract (2 house dust mite and 2 pollens), subcutaneous modified allergens (2 pollens), sublingual extract (2 house dust mites). The control group included two allergic patients submitted to subcutaneous injections of bacterial extract (1 patient--positive control), and aqueous solution (1 patient). At the same time that the therapeutic allergen was administered subcutaneously, the autologous labelled white cells were injected intravenously in a peripheral vein in the contralateral arm. A thoracic dynamic acquisition of 60 mins, 64x64 matrix, 2 frame/min, in anterior view was performed. Static acquisition for 256x256 matrix, during 5 mins each at 60, 90, 120, 180, 240, 300 and 360 mins after the administration of the radiolabelled leukocytes, in thoracic (anterior and posterior), and abdominal view were performed. During the examination, the local erythema was monitored. A similar procedure was undertaken for Sublingual administration of immunotherapy. RESULTS: The inflammatory activity at the site of SIT injection (aqueous depot extract) started in the first hour and the increase was time related. For modified allergen extract and sublingual SIT the activity was present since the beginning of the administration. The ascendant lymphatic drainage, which was directed to the homolateral axillary region, to the lymphoid tissue of the upper mediastinum and to the anterior region of the neck began earlier. Thoracic focalisations were present for all the patients, whereas bowel focalisations were only observed for the subcutaneous route of administration. Sublingual SIT did not induce axillary or intestinal inflammatory focalisations, even though the patients had swallowed the allergenic extract. The uptake coefficient in individualized areas corrected to the uptake coefficient background was also studied. CONCLUSIONS: For the subcutaneous route of administration, except for glutaraldehyde-modified allergen, the local inflammatory activity at the allergenic injection site was significantly higher in depth and was time dependent, maintaining activity even after complete disappearance of the erythema and/or wheal. These results express a prompt inflammatory involvement of the immune system with this allergenic therapy, which was unexpected until now. We also observed differences concerning allergic diseases, the type of allergenic extracts and routes of administration.

Specific immunotherapy for severe latex allergy.

We studied 4 patients (3 adult females + 13y old boy) with latex allergy. All patients had anaphylaxis related with latex and oral-latex-fruit syndrome. All 3 females had severe symptoms in the workplace. The boy had spina bifida with 9 previous surgeries and needed further surgical interventions. Positive skin prick tests (SPT), the presence of serum latex specific IgE (CAP-RAST, Pharmacia-Upjohn, Sweden- class 3 in the 3 females and class 4 in the boy) demonstrated the sensitisation. All 4 patients were treated with specific immunotherapy (SIT) with aqueous extract (ALK-ALK-ABELLO SA, Spain) administered subcutaneously at the hospital, by a modified rush schedule. A maintenance dose (MD) of 0.35_g protein was established according to the magnitude of local reactions (LRs). In one patient a higher dose induced the appearance of a systemic reaction (SR) 40 min after administration, which promptly remitted with treatment. After reaching MD, all 3 females remained assymptomatic at workplace. A challenge test with latex gloves was performed. Two months after MD was reached 2 females had no symptoms and one other had mild symptoms of rhinoconjunctivitis. The boy was subjected to a surgical intervention with no allergic reaction. We also observed a reduction on skin reactivity to latex in all patients by prick tests. We consider SIT with latex to be highly effective, safe and well tolerated provided we use this dose of the allergenic extract.

Síndrome de Wells. A propósito de dos casos / Well's syndrome

El síndrome de Wells o celulitis eosinofílica es una dermatosis inflamatoria caracterizada por placas edematosas, eritema-violáceas, infiltradas y discretamente pruriginosas. Con carácter autolimitado, desaparecen sin dejar secuelas en semanas o meses, y habitualmente presentan un curso recurrente. En ocasiones, se acompañan de manifestaciones sistémicas como fiebre o poliartralgias, siendo muy raro el compromiso simultáneo de otros órganos internos. En el 50 por ciento de los casos se acompañan de eosinofilia periférica, dato común pero no indispensable para el diagnóstico. La "figura en llama", cuadro histológico característico de este síndrome, no es patognomónico, ya que también está presente en diversas entidades que deben ser colocadas como diagnósticos diferenciales. Por tanto, la presencia concomitante de un cuadro clínico característico y hallazgos histopatológicos típicos es fundamental para el diagnóstico de celulitis eosinofílica. Se describen dos casos, en los que la realización de una historia clínica pormenorizada, con descripción detallada de las lesiones, complementada con el estudio histológico cutáneo, fue crucial para el diagnóstico de síndrome de Wells (AU)

Double-blind comparison of levocabastine nasal spray with sodium cromoglycate nasal spray in the treatment of seasonal allergic rhinitis.

Nasal levocabastine (0.5 mg/mL) was evaluated for efficacy and tolerance against sodium cromoglycate (20 mg/mL) in a 2-week double-blind trial in 27 and 29 patients with seasonal allergic rhinitis. Globally at 2 weeks, the investigators found a 74% response rate in the levocabastine patients versus a 50% response rate in the cromoglycate patients (P less than .10). Sneezing responded better to levocabastine than to cromoglycate according to three efficacy indicators derived from patient diary ratings of symptom severity: sum of severity scores over the total treatment period as a percentage of the theoretical maximum sum of severity scores (median: 19% versus 41%, P = .01); percentage of symptom-free days (median: 46% versus 22%, P less than .07); percentage of days with moderate or severe symptoms (median: 0% versus 29%, P = .004). Further, the percentage of days with moderate or severe runny nose was lower than in cromoglycate patients (median: 0% versus 25%, P = .09). Although no significant differences were found for itchy nose, blocked nose, and ocular symptoms, severities tended to be generally less under levocabastine than under sodium cromoglycate. Adverse experiences were low level and of similar incidence in the two groups. It is concluded that in a q.i.d. schedule, levocabastine nasal spray is more efficacious than sodium cromoglycate in relieving sneezing and that it is equally well tolerated.