Efficacy and safety of allergen immunotherapy in patients with allergy to molds: A systematic review.
Topic: Immunotherapy

Allergen immunotherapy (AIT) with mould extracts has been performed for many years but the final demonstration of its clinical efficacy is still missing, due to the small number of studies and their inconsistent results.

PICO
Population: Patients with allergy to molds
Intervention: Allergen immunotherapy with mould extracts
Comparison: Placebo or alternative treatment
Outcomes: Clinical efficacy and safety of allergen immunotherapy

Included studies:
title: Efficacy and safety of immunotherapy for allergies to Alternaria alternata in children.
abstract: The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents.
title: Alternaria allergy: a three-year controlled study in children treated with immunotherapy.
abstract: In this prospective controlled study, 39 children with Alternaria-induced asthma and/or rhinitis were followed-up over a 3-year period. Skin tests and RAST were positive to Alternaria tenuis only. All children were treated with specific Alternaria immunotherapy. The long-term results have shown that immunotherapy was successful in 80% of the children given more than 80.000 PNU. By contrast, the outcome of 40 selected controls also followed during the same period who did not receive immunotherapy was almost exactly the opposite. In addition to demonstrating the clinical effectivity of specific Alternaria immunotherapy, the authors stress the relationship between successful results, highest tolerated doses, and larger cumulative dosage, which is irrespective of the duration of the therapy.
title: Injective versus sublingual immunotherapy in Alternaria tenuis allergic patients.
abstract: Little knowledge is available on molds either from the environmental or clinical points of view. The latter is mainly due to the lack, until recent times, of purified and standardized extracts. Injective immunotherapy, largely used for patients allergic to mites and pollens, is regarded with some concern for molds. On the other hand, mold-related allergic symptoms (i.e.,from Alternaria tenuis) have in Italy an incidence of about 5 percent, mainly in young patients. We have therefore run a pilot study comparing the efficacy and safety of injective (SIT) and sublingual (SLIT) immunotherapy by administering the same purified and standardized extract of Alternaria tenuis to a total of 23 patients for two years, according to an open experimental plan. Excellent tolerance was shown to SLIT while four (two medium-grade) side effects appeared with SIT. Clinical improvement, subjectively stated comparing symptoms (mainly rhinitis) and drug consumption before and after the therapy, confirmed by an increase in the Specific Nasal Provocation threshold, was obtained with both therapies, but with a statistically significant difference in favour of SLIT. Skin reactivity and blood Alternaria tenuis specific IgE, total IgG and IgG changed in the SIT-treated group, while no statistically significant change was shown in the SLIT-treated group. These results are in good agreement with previous reports on SIT and SLIT with other inhalant allergens (mites, grasses), and suggest the potential use of SLIT for Alternaria allergy, mainly in young patients, when there are concerns about the safety of and compliance with the traditional injective therapy.
title: Diagnosis and immunotherapy of mould allergy. V. Clinical efficacy and side effects of immunotherapy with Cladosporium herbarum.
abstract: A placebo-controlled, double-blind study of immunotherapy with the mould species Cladosporium was performed in 22 adult asthmatics. The diagnosis of Cladosporium allergy was based on a combination of bronchial provocation test and daily symptom score in the Cladosporium season. An aqueous preparation of a potent, biologically standardized and purified extract was used in a clustered dose-increase regimen. The clinical efficacy was evaluated by a combination of symptoms (asthma score + peak flow) and consumption of antiasthmatic medication. The mean changes in symptoms and medication consumption over a 10-week registration period (peak Cladosporium season) in 1982 after 5-7 months of immunotherapy were compared with the corresponding 1981 pretreatment 10-week period. A significant (P = 0.03) difference in terms of "improved", "unchanged" and "deteriorated" patients in favour of Cladosporium treatment was found. Approximately 80% in the Cladosporium group showed improved/unchanged symptoms contrary to 30% of the placebo treated. Side effects were observed frequently but only in the Cladosporium-treated. About 70% experienced a large local reaction and 100% had episodes of asthma during dose-increase phase. Only a few severe systemic reactions occurred. Based on the clinical efficacy of the treatment we consider immunotherapy with Cladosporium feasible for highly specialized clinics.
title: A double-blind, multicenter immunotherapy trial in children, using a purified and standardized Cladosporium herbarum preparation. I. Clinical results.
abstract: A double-blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and standardized Cladosporium herbarum allergen preparation. Thirty children with a clinical history suggesting mould-induced asthma and/or rhinoconjunctivitis were included. The diagnosis was confirmed by positive skin prick test and Phadebas RAST as well as positive bronchial and/or conjunctival provocation test to Cladosporium herbarum. Immunotherapy was given for 10 months in a double-blind manner to randomized groups with either Pharmalgen/Cladosporium herbarum preparation or histamine placebo. Allergic side effects to injections were common, especially during the peak of the mould season (July-September in Scandinavia). In the active group, 13/16 patients experienced general reactions during the first 10 months of treatment. After 6 months of treatment, eye, nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups, maybe because most of the children were also sensitive to many other allergens, including Alternaria alternata. However, medication scores were significantly lower in the treated group (P less than 0.01). Bronchial (P less than 0.01) and conjunctival sensitivity (P = 0.01) were significantly reduced in the Cladosporium-treated group but not in the placebo group after 10 months of treatment. This is the first double-blind clinical trial showing the clinical efficacy of immunotherapy in children with mould-induced asthma.
title: [Immunotherapy with an oral Alternaria extract in childhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro parameters].
abstract: Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/micro g protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response.
title: Clinical evolution of patients with respiratory allergic disease due to sensitisation to Alternaria alternata being treated with subcutaneous immunotherapy.
abstract: Sensitisation to Alternaria is a cause of respiratory disease in Spain, particularly in childhood, but it is also a significant marker of the severity of this disease. Therefore, the use of an aetiological treatment (allergen specific immunotherapy) is essential, and both subjective and objective clinical parameters should be used to follow up this treatment.
title: Double-blind, placebo-controlled study of Alternaria alternata immunotherapy: clinical efficacy and safety.
abstract: Allergen-specific immunotherapy (ASIT) with fungal extracts has been beset by safety and efficacy problems, which result mainly from qualitative and quantitative variations. Little has been published on the safety and efficacy of these extracts. The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract. A total of 28 patients were selected with rhinitis and/or bronchial asthma because of Alternaria allergy and monosensitization to molds. The patients were randomized to an active ASIT or placebo group, both groups on a conventional immunotherapy schedule (increasing weekly doses until maintenance dose and then monthly doses). Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system. Clinical efficacy was analyzed for a year with symptom/medication diary cards, peak expiratory flow (PEF) measures, clinical severity score, severity of symptoms (visual analog scale), subjective evaluation of treatment by the patient and the physician, and a quality of life questionnaire. Twenty-three patients completed the study; all reached the established maintenance dose with only two mild adverse reactions in the whole sample. Significant improvements were found after 6 months in respiratory symptoms in the active treatment group, and in all symptoms in both groups. PEF increased significantly in the active treatment group but not in the placebo group. The severity of asthma decreased in the active treatment group, and the severity of rhinitis decreased in both groups. Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group, but only after 12 months in the placebo group. Physicians judged the disease course as significantly better in the active treatment group. ASIT with the A. alternata extract was safe, with clinical improvements after one year of treatment.
title: Sublingual immunotherapy for Alternaria-induced allergic rhinitis: a randomized placebo-controlled trial.
abstract: Respiratory allergy due to Alternaria is a relevant clinical problem, and specific immunotherapy may represent a viable treatment option. Sublingual immunotherapy (SLIT) is safe and effective, but data for Alternaria are lacking.
title: Multicenter double-blind comparative study of terfenadine and cetirizine in hay fever.
abstract: The efficacy and safety of terfenadine in the management of hay fever were compared with those of cetirizine in a multicenter, double-blind, parallel-group study, carried out during the 1990 spring pollen season. The patients were randomly assigned to one of two groups of treatment, 70 patients being given terfenadine 120 mg, and 72 patients cetirizine 10 mg, once daily for 7 days. The severity of the main symptoms was evaluated at baseline and after treatment by a 4-point rating scale. In addition, the overall symptom severity was recorded daily by the patient on a diary card. Both terfenadine and cetirizine produced significant relief of symptoms by the end of treatment, with a decrease in symptom severity ranging from 46 to 69% for terfenadine and from 40 to 55% for cetirizine. Adverse effects experienced by terfenadine- and cetirizine-treated patients were mainly drowsiness, with minor differences between the two groups. The results of this study confirmed previous experiences, showing that both terfenadine and cetirizine once daily should be regarded as effective drugs for the management of hay fever.
title: Efficacy of sublingual specific immunotherapy in patients with respiratory allergy to Alternaria alternata: a randomised, assessor-blinded, patient-reported outcome, controlled 3-year trial.
abstract: Alternaria alternata (AA) sensitisation is a common cause of respiratory allergies such as rhinitis and asthma. So far there are no controlled double-blind trials evaluating the efficacy and safety of specific sublingual immunotherapy (SLIT) in AA allergies.