[Cross-reactivity in allergic fungal sinusitis. Case report]. / Reactividad cruzada en sinusitis alérgica fúngica. Reporte de caso.

BACKGROUND: The presence of allergic mucin in allergic fungal sinusitis (AFS) is a manifestation that identifies it as a hypersensitivity process. AFS has a phenomenon of cross-reactivity to IgE-bound proteins having at least two shared epitopes. CLINICAL REPORT: A 13-year-old male with nasal obstructive symptoms of three years of evolution. An obstructive mass was identified in the sinuses through physical examination and CT. In endoscopic surgery, the left nostril polyp was identified with the macroscopic appearance of allergic mucin; the polyp was resected. Final histopathological examination using periodic acid-Schiff and Grocott's methenamine silver staining indicated Aspergillus. Two weeks after surgery, percutaneous tests showed sensitization to Alternaria, Helminthosporium sativum, and Deramatophagoides farianae with negativity to Aspergillus fumigatus. CONCLUSIONS: The absence of significant titers of specific IgE antibodies to Aspergillus fumigatus was the evidence that the hypersensitivity response was triggered by a pathogen other than that isolated in histopathological study, which coupled with positive tests for other fungi may be explained by the cross-reactivity phenomenon in a phenomenon of likely hypersensitivity.

Antecedentes: La presencia de mucina alérgica en la rinosinusitis alérgica fúngica (RAF) es una manifestación que la identifica como un proceso de hipersensibilidad. En la RAF existe un fenómeno de reactividad cruzada entre proteínas unidas a IgE que tienen al menos dos epítopes compartidos. Caso clínico: Varón de 13 años de edad con síntomas obstructivos nasales de tres años de evolución. Por exploración física y tomografía se identificó masa obstructiva en los senos paranasales. En la cirugía endoscópica, en la fosa nasal izquierda se identificó pólipo con aspecto macroscópico de mucina alérgica; el pólipo fue resecado. El examen histopatológico final mediante tinciones con ácido peryódico de Schiff y metenamina plata de Grocott indicó Aspergillus. Dos semanas después de la cirugía, las pruebas percutáneas mostraron sensibilización a Alternaria alternata, Helminthosporium sativum y Deramatophagoides farianae, con negatividad a Aspergillus fumigatus. Conclusiones: La ausencia de títulos significativos de anticuerpos IgE específicos para Aspergillus fumigatus constituyó la evidencia de que la respuesta de hipersensibilidad fue desencadenada por un patógeno distinto del aislado en el estudio histopatológico, que aunada a las pruebas positivas para otros hongos puede explicarse por el fenómeno de reactividad cruzada en un probable fenómeno de hipersensibilidad.

Fungi allergens produced by solid-state fermentation process: optimization and allergen characterization.

Allergenic extracts were produced from Drechslera (Helminthosporium) monoceras biomass cultured by solid-state fermentation using wheat bran as the substrate. The main fermentation variables were selected by statistical design, and the optimized biomass yield (1.43 mg/[g of dry substrate d]) was obtained at pH 9.5 and 45.8% moisture. The allergenic extracts were produced from crude extract by protein precipitation and polyphenol removal. Proteins in the range of 16-160 kDa were identified in the extracts. Their reactions in patients were characterized by in vivo cutaneous tests (positive in 40% of the atopic patients) and by dot-blotting assays.

Sensitivity to fungal allergens is a risk factor for life-threatening asthma.

BACKGROUND: Previous studies have suggested that sensitivity to Alternaria and Cladosporium may be risk factors for life-threatening asthma. We have investigated this by studying the relationship between skin tests for fungal spores and admission to an intensive care unit (ICU) for asthma. METHODS: Skin prick tests for fungal spores (Alternaria tenuis, Cladosporium cladosporoides, Helminthosporium maydis, and Epicoccum nigrum), cat dander, house-dust mite (Dermatophagoides pteronyssinus), and a seven-grass mix were performed in three groups of patients: patients admitted to an ICU with an attack of asthma; those who had received emergency treatment for asthma but had not been admitted to an ICU, and those who had never required emergency treatment for their asthma. RESULTS: Twenty of 37 patients (54%) admitted to the ICU had a positive skin test for one or more fungal allergens compared with 15/50 patients (30%) in each of the other groups (P=0.005). The ICU patients were no more likely to have positive skin tests for the grass mix, cat dander, or house-dust mite than the other patients. CONCLUSIONS: A positive skin test for fungal allergens is a risk factor for admission to an ICU with an acute attack of asthma.

Outcomes after discontinuing immunotherapy for allergic fungal sinusitis.

Although the treatment of allergic fungal sinusitis with specific immunotherapy after surgical intervention has proved successful, the question of what happens when such injections are discontinued remains unanswered. In this initial, admittedly small series, no recurrence has been noted in follow-up of 7 to 17 months.

Immunotherapy for allergic fungal sinusitis: three years' experience.

Since August 1994, we have treated patients with histologically proven allergic fungal sinusitis with surgery followed by immunotherapy, employing fungal and nonfungal antigens to which hypersensitivity has been demonstrated. Our results continue to be encouraging. Not only have we encountered no indication that fungal immunotherapy has worsened these patients' condition or caused a recurrence of disease, we have confirmed dramatic improvement in these patients compared with the generally accepted course of this disease. Of 11 patients who have received immunotherapy for 1 to 3 years (mean 28 months), none has required regular or frequent treatment with a single brief course of systemic steroids, and only three are receiving topical nasal steroids. No repeat surgeries for recurrent allergic fungal sinusitis have been required in the treatment group. This combination of surgery and immunotherapy has continued to prove beneficial, and we urge others to consider this approach to therapy.

Prevalence of mold-specific immunoglobulins in a Midwestern allergy practice.

Mold allergy surveys are an important part of the correct identification and treatment of mold allergies. This study included 100 patients who were referred to a Midwestern allergy clinic for the evaluation of rhinitis, suspected to be of allergic origin. An in vitro screening test for allergen-specific IgE (ImmunoCAP) comprised of 10 allergens, including Candida, Aspergillus, Helminthosporium, and Alternaria, was used. To assess the seasonal distribution of mold allergies, we randomly selected 8 patients out of the 100 from each season during which the clinical contact occurred, and we tested them for 14 varieties of mold. The overall incidence of mold allergy in atopic subjects was 44%. The most common molds were (in descending order of frequency) Alternaria, Helminthosporium, Aspergillus, Candida, and Curvularia. Mold allergy was diagnosed most frequently in the winter; the second highest period was the fall. Population surveys of IgE antibody sensitization by in vitro techniques can provide useful information about fungal allergy.

Biochemical, antigenic and allergenic characterization of crude extracts of Drechslera (Helminthosporium) monoceras.

In a previous study with airborne mould extracts we verified that Drechslera (Helminthosporium) monoceras presented stronger reactions than those presented by 42 other moulds isolated in São Paulo city. In the present study, we evaluated the biochemical composition and the antigenicity of crude extracts obtained from vegetative and conidial stage of D. monoceras using Czapeck broth (CB) modified and tris-HCl for extraction. The maximum values of total proteins and lipids were verified in the crude extract obtained in the 28th day of growth, and maximum values of carbohydrates were observed in the extracts of the 16th, 22nd and 26th days. The fractionated proteins by SDS-PAGE presented bands with molecular weights between 14.4 to 67 Kd; the 28th day extract showed a larger number of bands. The carbohydrates and amino acids were characterized by thin-layer chromatography. The antigenicity of the crude extracts was verified by immunodiffusion reaction in agar against rabbit hyperimmune sera. Precipitation lines were observed in all studied extracts and common antigenic molecular populations. Based on the above results, the 28th day extract was selected to verify the induction of IgE antibody responses in immunizations of Balb/c and cAF-1 mice, and titer by passive cutaneous anaphylaxis test using Wistar rats. The maximum titers obtained were 160 in cAF-1 mice and 1.280 in Balb/c mice. The results suggest that the 28th day extract contains allergenic fractions and should be chosen for future studies related to fractionation, characterization and standardization in diagnostic methods and immunotherapy.

Effect of mixing allergenic extracts containing Helminthosporium, D. farinae, and cockroach with perennial ryegrass.

Allergenic extracts used for immunotherapy often contain mixes of different allergens. Studies have shown that certain allergenic extracts contain enzymes that can cause a decrease in grass pollen allergenicity when mixed with grass extracts. Glycerin and buffered saline with phenol (BSP) extracts containing Helminthosporium interseminatum, D. farinae, and cockroach were mixed with perennial ryegrass extracts and analyzed 7, 30, 60, and 90 days after mixing to determine the mixing effect of these extracts on the ryegrass pollen potency. Analysis was performed using RAST inhibition, SDS-PAGE and, to determine biologic potency, a quantitative intradermal skin test technique. All tests showed significant decreases in ryegrass potency when mixed with Helminthosporium and cockroach. This decrease was not seen with the D. farinae mix. Glycerin seemed to have some protective effect. Even in the situation showing the most decrease in ryegrass potency (Helminthosporium mixed with ryegrass in a BSP extract), the resulting extract still contained an estimated biologic potency of 10,000 AU/mL. This may explain why such mixes, which have been used clinically for many years, appear to give adequate therapeutic results. The study also suggest that clinicians may be well advised not to mix grass pollen extracts with extracts that may contain proteolytic enzymes.

Evidence of IgE-mediated hypersensitivity in allergic fungal sinusitis.

Despite documentation of specific immunologic hypersensitivity in a few case reports, controversy continues as to the role of allergy versus true infection in the clinical entity of allergic fungal sinusitis (AFS). Using a modified radioallergosorbent test (RAST) to multiple fungal antigens, 16 patients meeting the histologic criteria of AFS and with positive fungal cultures were compared to 5 control patients with similar preoperative clinical findings but without histologic or culture evidence of AFS. All patients were immunocompetent and none demonstrated histologic evidence of tissue invasion. All AFS patients were RAST-positive to at least one fungal antigen in the family of their cultured organism with positive defined as class 2 or greater. No control patient was RAST-positive to either dematiaceous or Aspergillus fungal antigens. Thus, modified RAST testing can aid in the routine clinical diagnosis of AFS, and it provides further serologic evidence for a type I hypersensitivity in the pathogenesis of AFS.

Clinical significance of molds newly available for radioallergosorbent testing.

Three years of weekly Rotorod airborne allergen reports from Corpus Christi, Texas, were reviewed. Five of 10 newly available airborne molds for radioallergosorbent testing (RAST) were present in significant numbers. Three hundred seventy-five mold RAST evaluations were expanded to include the five old and these five new molds. Except for Alternaria, the frequency of and allegenic response to the new molds were generally greater than those for the five old molds. The usual Alternaria-Cladosporium mold screen proved less satisfactory when these five new molds were added to the mold battery; however, the addition of Helminthosporium to the screen corrected this deficiency. Cross-reactivity production of false-positive responses seems unlikely because of frequent significant variance in RAST scores from mold to mold in the same patient.

Evaluation of the cause of nasal and ocular symptoms associated with lawn mowing.

A number of individuals with perennial or seasonal rhinoconjunctivitis state that their symptoms may suddenly worsen on exposure to lawn mowing. Many allergists have believed that this was related to the agitation of molds deposited on the grass. We studied 50 consecutive new patients with rhinitis using history, skin testing, total and specific IgE assays, and nasal smears. Twenty-five patients gave histories of minimal or no change in their nasal symptoms with exposure to lawn mowing, whereas 11 patients had definite, but mild, symptoms, and 14 patients had severe symptoms. Positive skin tests to grasses, trees, and weed pollens were more frequent in those patients with symptoms exacerbated by lawn mowing (p less than 0.03). Symptomatic patients also had higher serum concentrations of total IgE (p less than 0.008) and grass-pollen specific IgE (p = 0.0004). The frequencies of positive skin tests to ragweed pollens, house dust, molds, and grass leaves, as well as the percentage of nasal eosinophils, were not different in the symptomatic and asymptomatic groups. No significant association was found between symptoms and IgE antibodies to molds or grass-leaf extract. We believe that the increased nasal and ocular symptoms coincident with lawn mowing are allergic phenomena significantly associated with skin test sensitivity and specific IgE antibodies to grass pollens but not with sensitivity or specific IgE to molds or grass-leaf extract.

Incidence of fungal spores at the homes of allergic patients in an agricultural community. II. Correlations of skin tests with mold frequency.

A mold survey in and out of the homes of 145 allergy patients was conducted over the course of a year and frequency of mold recovery was correlated with skin test reactivity in 131 of these patients. The highest percentage correlation with positive skin test and finding mold in the home was with Cladosporium. Penicillium and Alternaria, while Helminthosporium, Fusarium, Aureobasidium (Pullularia) and Mucor each had correlations of one percent or less. The 0-10 age group was the most skin test reactive to molds in general while the over-50 age group was the least reactive. The percentage of patients sensitive to Alternaria also responding to other mold antigens was the highest with Helminthosporium. Since Helminthosporium was rarely recovered in this survey the data suggest that cross reactivity and not dual reactivity between Alternaria and Helminthosporium is occurring.