Unusual aspects of allergic bronchopulmonary fungal disease: report of two cases due to Curvularia organisms associated with allergic fungal sinusitis.

We report two cases of allergic bronchopulmonary fungal disease (ABPFD) caused by Curvularia sp and associated with allergic fungal sinusitis (AFS). Curvularia lunata was cultured in one case and Curvularia senegalensis was cultured in the other. Based on these cases and a review of the literature, we discuss unusual clinical and pathologic features that can occur in ABPFD. Unusual clinical aspects of ABPFD include associated AFS, absence of asthma, progression to Churg-Strauss angiitis and granulomatosis, concomitant hypersensitivity pneumonitis, and underlying cystic fibrosis. Atypical pathologic features that may occur in ABPFD include follicular bronchiolitis, xanthomatous bronchiolitis, limited tissue invasion, fungus balls, and association with unusual fungi. Prominent follicular bronchiolitis and xanthomatous bronchiolitis were misleading histologic features in one of our cases and led to a delay in recognition of the diagnosis. Both patients presented primarily with AFS; ABPFD was detected subsequently. This suggests that a small subset of patients with AFS may be at risk for ABPFD. The goal of this review is to increase awareness of unusual clinical and pathologic manifestations of ABPFD. It is hoped that this will result in accurate diagnosis and proper therapy, especially for patients who present with atypical features. Unusual fungal species should be considered in patients who have clinical findings compatible with ABPFD but who do not demonstrate immunologic reactivity to Aspergillus sp, especially Aspergillus fumigatus. In addition, ABPFD should be considered in patients with AFS who develop new pulmonary lesions.     

The spectrum of allergic fungal diseases of the upper and lower airways

Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient’s risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient’s asthma should be sought to decrease worsening progression of the disease.     

Concomitant allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis: a review of an uncommon association*

BACKGROUND: Although thought to have common immunopathological processes, concomitant occurrence of allergic bronchopulmonary aspergillosis (ABPA) and allergic Aspergillus sinusitis (AAS) appears to be rarely reported as to date only five detailed case reports are available. OBJECTIVE: To present a review of seven cases of concomitant ABPA and AAS, three of whom were earlier reported for their unusual presentations. METHODS: Patients with ABPA with nasal symptoms were evaluated radiologically. Consent was taken for antral wash and/or Caldwell-Luc operation in those with radiological evidence of sinusitis and the material was sent for histopathological and mycological studies. RESULTS: Of the 95 patients with ABPA, 22 had radiological evidence of sinusitis. Nine consented to surgery, seven of whom were diagnosed as concomitant AAS. Nasal symptoms preceded chest symptoms in two patients, vice versa in one and occurred simultaneously in four. Familial occurrence of ABPA, middle lobe syndrome and collapse with effusion along with an operated aspergilloma were seen in one patient each. Transient pulmonary infiltrates and central bronchiectasis were seen in all patients. Computed tomography of the paranasal sinuses, carried out in six patients, revealed mucosal thickening with hyperdense lesions, without any bony erosion or destruction. All patients had positive skin tests, positive precipitin study and raised total and specific IgE. Allergic mucin was seen in all patients, fungal hyphae in five, and culture grew Aspergillus spp. in four. All patients responded favourably to oral prednisolone. CONCLUSION: Concomitant occurrence of ABPA and AAS seems to be infrequently recognized. Since asthma and sinusitis are often seen by two different specialities, the occurrence of AAS in ABPA and ABPA in AAS may easily be overlooked.     

变应性真菌性鼻窦炎临床病理分析

目的 探讨变应性真菌性鼻窦炎(AFS)的临床病理特征,提高对AFS的认识和病理诊断水平.方法 回顾并分析首都医科大学附属北京同仁医院2002-2006年36例AFS的临床病理和影像学资料,应用阿尔辛蓝-过碘酸雪夫(AB-PAS)、环六亚甲基四胺银(GMS)特殊染色及黏蛋白5B(MUC5B)免疫组织化学(SP法)染色标记真菌,同时选取AFS新鲜活检组织lO例进行透射电镜观察.结果 36例AFS中,男21例,女15例,发病年龄11～53岁.多具有变应性疾病病史.CT平扫示受累的鼻窦充满软组织影,伴斑片状高密度影,窦壁骨质可出现压力性骨破坏.实验室检查:一种或多种真菌抗原皮试阳性(31/36);血清学检查总IgE和(或)真菌特异性lgE增高(20/36);外周血嗜酸性粒细胞数增多(23/36).真菌培养10例阳性.组织病理学:大体典型病变为黏稠的"油灰样"分泌物,镜下为特征性的"嗜酸性黏蛋白",AB-PAS及GMS染色、MUC5B免疫组织化学染色真菌均着色.透射电镜可见嗜酸性粒细胞脱颗粒现象.结论 "嗜酸性黏蛋白"是AFS最具特征性的病理学表现,建议采用AB-PAS、GMS特殊染色及MUCSB免疫组织化学染色等多种方法 联合标记真菌;需对临床症状、影像学特点、实验室检查及病理学表现等多个方面进行综合判断以得出正确诊断.     

Fungi and allergic lower respiratory tract diseases

Asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the United States. In patients with moderate and severe persistent asthma, there is significantly increased morbidity, use of health care support, and health care costs. Epidemiologic studies in the United States and Europe have associated mold sensitivity, particularly to Alternaria alternata and Cladosporium herbarum, with the development, persistence, and severity of asthma. In addition, sensitivity to Aspergillus fumigatus has been associated with severe persistent asthma in adults. Allergic bronchopulmonary aspergillosis (ABPA) is caused by A fumigatus and is characterized by exacerbations of asthma, recurrent transient chest radiographic infiltrates, coughing up thick mucus plugs, peripheral and pulmonary eosinophilia, and increased total serum IgE and fungus-specific IgE levels, especially during exacerbation. The airways appear to be chronically or intermittently colonized by A fumigatus in patients with ABPA. ABPA is the most common form of allergic bronchopulmonary mycosis (ABPM); other fungi, including Candida, Penicillium, and Curvularia species, are implicated. The characteristics of ABPM include severe asthma, eosinophilia, markedly increased total IgE and specific IgE levels, bronchiectasis, and mold colonization of the airways. The term severe asthma associated with fungal sensitization (SAFS) has been coined to illustrate the high rate of fungal sensitivity in patients with persistent severe asthma and improvement with antifungal treatment. The immunopathology of ABPA, ABPM, and SAFS is incompletely understood. Genetic risks identified in patients with ABPA include HLA association and certain T(H)2-prominent and cystic fibrosis variants, but these have not been studied in patients with ABPM and SAFS. Oral corticosteroid and antifungal therapies appear to be partially successful in patients with ABPA. However, the role of antifungal and immunomodulating therapies in patients with ABPA, ABPM, and SAFS requires additional larger studies.     

Medical treatment of allergic fungal sinusitis.

LEARNING OBJECTIVES: This review of allergic fungal sinusitis (AFS) will enable the reader to (1) differentiate AFS from the other forms of fungal sinusitis, (2) understand AFS pathophysiology, (3) recognize AFS clinical presentation, (4) prepare an effective treatment and follow-up strategy, and (5) avoid diagnostic and treatment pitfalls. DATA SOURCES: All English language MEDLINE articles that cross-referenced allergy, fungal, and sinusitis from 1983-present. Other MESH words referenced included: antibodies, fungal; fungus diseases; IgE; spores, fungal; rhinosinusitis. Additional referenced articles, published abstracts, and conference proceedings were also utilized. STUDY SELECTION: All case reports, studies, and review articles. RESULTS: Allergic fungal sinusitis is a distinct form of non-invasive fungal sinusitis. It is under-diagnosed, and incidence varies by region. Dematiaceous fungi predominate. In the southwestern United States, Bipolaris spicifera is the most common cause. Patients present with nasal polyps, rhinosinusitis, and occasionally proptosis. CT scans show hypertrophic sinusitis and often hyperattenuating allergic mucin within the sinus cavities. Extra-sinus extension of disease is common. Surgical histopathology shows eosinophilic-lymphocytic mucosal inflammation and inspissated allergic mucin containing non-invasive fungal hyphae. All patients are atopic and have positive allergy skin tests to the AFS organism. Total serum IgE levels are usually elevated. AFS immunopathophysiology is analogous to allergic bronchopulmonary aspergillosis. Treatment requires surgery, postoperative oral corticosteroids (OCS), and aggressive allergy management including allergen immunotherapy. Oral corticosteroids reduce disease activity and forestall the need for recurrent sinus surgery. Postoperative changes in total serum IgE mirror the clinical status and may predict disease recurrence. Patients should be cooperatively followed by the medical specialist and surgeon because early sinus surgery for recurrence, together with aggressive medical management, gives the best outcome. CONCLUSIONS: Allergic fungal sinusitis is a new allergic disorder with recognizable clinical and histopathologic findings. Treatment requires aggressive allergy management, postoperative OCS, monitoring of total serum IgE, and medical/surgical co-management.     

Aspergillus fumigatus: Identification of 16, 18, and 45 kd antigens recognized by human IgG and IgE antibodies and murine monoclonal antibodies

The immunochemical properties of antigens produced by Aspergillus fumigatus were investigated with biochemical purification techniques in conjunction with the production of murine monoclonal antibodies (MAbs) and binding studies with human IgG and IgE antibodies. A. fumigatus antigens were partially purified by gel filtration and hydrophobic interaction chromatography on phenyl-Sepharose. Two fractions that eluted with either 2 mol/L or 0.15 mol/L of NaCl demonstrated strong binding to human IgG and IgE antibodies. Immunoprecipitation analysis with IgG antibodies from six patients with different Aspergillus-related diseases demonstrated that the 2M and 0.15M fractions contained major antigens of molecular weight 18 kd (Asp f I) and 45 kd, respectively. The ¹²⁵I-labeled 2M fraction was used to compare IgG antibodies to A. fumigatus in sera from 25 patients with Aspergillus-related diseases. IgG antibodies were significantly higher in patients with allergic bronchopulmonary aspergillosis (geometric mean, 437 U/ml) than in patients with asthma (geometric mean, 14 U/ml; p < 0.001), but undetectable (<5 U/ml) in 43148 control subjects. A good correlation was found between levels of IgG antibodies to the ¹²⁵I-labeled 0.15M fraction and the ¹²⁵I-labeled 2M fraction in sera from 106 patients with cystic fibrosis (r = 0.77; p < 0.001). Five murine IgG MAbs and two IgM MAbs were raised against the 2M fraction, and immunoprecipitation with the IgG MAb demonstrated two distinct antigens within the 2M fraction, Asp f I, and a 16 kd antigen. The results of a solid phase RIA with IgG MAb 4A6 demonstrated that ≈85% of A. fumigatus-allergic patients with allergic bonchopulmonary aspergillosis had IgE antibodies to Asp f 1. The three protein antigens defined in these studies are useful probes for investigating the immunopathogenesis of diseases associated with colonization by A. fumigatus.     

Allergenic cross-reactivity of Curvularia lunata with other airborne fungal species

BACKGROUND: Curvularia lunata is an important fungus for respiratory allergic disorders. Previous studies indicated cross-reactivity of Curvularia with other fungi. However, the cross-reactive allergenic component (s) were not identified. The present work was carried out to study the shared allergenic components of C. lunata and others. METHODS: Cross-reactivity studies were performed using pooled hypersensitive patient sera to C. lunata by ELISA, immunoblot, immunoblot inhibition and ELISA inhibition. RESULTS: Many C. lunata sensitive patients showed positive skin test to five other fungi. Alternaria alternata exhibited maximum (68%) whereas Cladosporium herbarum showed the least (17%) skin reactivity. Immunoblots of fungal extracts with pooled sera showed common proteins. Fusarium solani and C. herbarum showed negligible IgE binding. IgE ELISA inhibition with C. lunata showed 92% inhibition whereas A. alternata and E. nigrum showed 84% and 63%, respectively. Immunoblot inhibition with self protein showed complete loss of IgE-binding activity. Proteins of 26, 31, 38, 45 and 50 kDa of C. lunata were inhibited by A. alternata and E. nigrum, whereas A. fumigatus inhibited 26, 45 and 50 kDa proteins. CONCLUSIONS: Significant allergenic cross-reactivity exists among proteins of C. lunata, A. alternata and E. nigrum. Proteins of 26, 31, 38, 45 and 50 kDa are shared allergens in these fungi.     

Sensitization to recombinant Aspergillus fumigatus allergens in allergic fungal sinusitis.

BACKGROUND: Allergic bronchopulmonary mycosis is primarily caused by Aspergillus fumigatus. Despite similarities, allergic fungal sinusitis (AFS) is thought to be caused by various fungi. OBJECTIVE: Identify fungal elements in AFS allergic mucin and determine the prevalence of specific immunoglobulin (Ig)E to recombinant A. fumigatus allergens (rAsp) in AFS patients. METHODS: Allergic mucin from 17 definitive and 10 probable AFS patients were histologically examined for fungal elements. Sera from 18 definitive AFS patients, 10 probable AFS patients, 6 chronic sinusitis patients, and 5 A. fumigatus-allergic patients were tested for specific IgE to A. fumigatus and five rAsps. RESULTS: Ten of the 17 definitive cases had hyphae morphologically resembling Aspergillus or Fusarium spp. One probable AFS patient had similar findings. Of definitive patients, 94% (17 of 18) showed A. fumigatus-specific IgE (> or = 0.35 kUa/L), and 67% were positive to one or more rAsp. Four of 10 probable patients demonstrated A. fumigatus-specific IgE, and 2 had IgE to one or more rAsp. The definitive group had greater mean A. fumigatus IgE (P < 0.05) versus the probable and chronic sinusitis groups. The definitive group's rate of IgE to the rAsps was statistically greater. All definitive patients with Aspergillus or Fusarium spp. in situ had A. fumigatus-specific IgE, and 7 of 10 had IgE to at least one rAsp. CONCLUSIONS: Most definitive AFS patients have A. fumigatus-specific IgE and many have specific IgE to rAsps. Many also demonstrate Aspergillus spp. or Fusarium spp. in situ. Findings suggests that A. fumigatus is an important causative agent in AFS in the southeast United States.     

Allergic fungal sinusitis in children.

BACKGROUND: Allergic fungal sinusitis (AFS) has been characterized in adults presenting with chronic sinusitis. Rare reports allude to a similar disease in children. OBJECTIVE: To characterize the features of AFS in children. METHODS: Children referred to otolaryngology clinics at Arkansas and LeBonheur Children's Hospitals for chronic sinusitis during a 12-year period were studied. This retrospective analysis reviews the following: clinical presentation, laboratory evaluations, radiographic and pathologic findings, and surgical intervention. Twenty patients (age range, 7-18 years; mean age, 12.5 years; median age, 16 years) met previously published criteria for AFS. Thirteen patients were male and 7 were female. Thirteen were African American and 7 were white. RESULTS: Presentation at diagnosis included the following: atopy (n = 20), nasal symptoms (n = 20), recurrent sinusitis (n = 18), nasal polyps (n = 18), recurrent headaches (n = 12), asthma (n = 11), proptosis (n = 10), and ocular symptoms (n = 10). All had radiographic evidence of sinusitis and allergy to fungal organisms. IgE levels were elevated in 8 of 9 patients, and 10 of 15 patients had eosinophilia. Surgical specimens demonstrated allergic mucin (n = 11), Charcot-Leyden crystals (n = 2), hyphae or fungal debris (n = 9), and fungal growth (n = 17). All patients underwent endoscopic sinus surgery, with 11 requiring multiple surgical procedures. Postoperatively, 19 patients received intranasal and oral steroids, and all had nasal saline washes. Eleven patients (9 who had undergone multiple surgical procedures) were treated with immunotherapy. Relapse was seen in 55% of patients at 1 year of follow-up. CONCLUSION: AFS presents with a higher incidence of proptosis in children when compared with adults. Typically, AFS occurs in atopic children with refractory sinus disease, requiring a high index of suspicion for evaluation and aggressive treatment.     

Role of allergic reactions of peripheral blood leukocytes in the pathogenesis of experimental allergic (pertussis) encephalomyelitis

After sensitization of guinea pigs with an oily suspension ofBordetella pertussis cells, starting from the 14th day a persistent leukocytosis and lymphocytosis was observed in the peripheral blood of the animals. The leukocytic formula showed a shift to the left. On contact between the blood leukocytes and specific brain antigen bothin vivo andin vitro the leukocytolysis and allergic changes in the leukocytes observed in the late stages of sensitization (in the period of clinical manifestations of experimental allergic encephalomyelitis — EAE) took place mainly at the expense of the granulocytes. These changes are tentatively attributed to antibrain antibodies present in the blood in this period of EAE, i. e., to a combination of allergic reactions of immediate type and reactions of delayed type in a common mechanism of development of pertussis EAE.Laboratory of Allergy, I. I. Mechnikov Scientific-Research Institute of Vaccines and Sera, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. V. Shmidt.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 320–324, March, 1977.     

Molecular modulation of allergic responses

The pathophysiology of allergic diseases involves an intricate network of molecular and cellular interactions. Elevated levels of serum IgE– and T_H2 cytokine–associated eosinophilic inflammation characterize allergic diseases and provide potential targets for immunomodulation. Recent evidence that antigen-induced allergic responses can be modulated in rodents by mucosal transfer of T_H1 -cytokine genes or by immunization with plasmid DNAs encoding the sensitizing antigens suggests promising new prophylactic or therapeutic approaches. Innovative research in mapping the regulatory pathways that typify the atopy network will provide a deeper understanding of the molecular mechanisms underlying these diseases and facilitate the design of more specific and efficacious modulation strategies. (J Allergy Clin Immunol 1998;102:887-92.)     

Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis

Background: Intranasal corticosteroids, such as budesonide and fluticasone propionate, are widely prescribed in the treatment of perennial allergic rhinitis. Once daily budesonide dry powder and fluticasone propionate aqueous suspension have been found to provide similar efficacy in controlling symptoms of perennial allergic rhinitis. Objective: The purpose of this study was to assess the efficacy and safety of treatment with once daily budesonide aqueous nasal spray. Methods: This study involved a multicenter, blinded, randomized, parallel-group, placebo-controlled trial of adults with perrenial allergic rhinitis. Patients (n = 273) recorded daily nasal symptoms for 8 to 14 days (baseline) and 6 weeks (treatment). Results: Budesonide decreased combined symptoms to a significantly greater extent than did fluticasone (P = .03); both treatments significantly decreased mean combined nasal symptoms scores compared with placebo. Of the 3 nasal symptoms assessed (ie, nasal blockage, runny nose, and sneezing), nasal blockage was significantly (P = .009) more decreased with budesonide compared with fluticasone. Both treatments also significantly improved runny nose and sneezing compared with placebo. Improvement in combined nasal symptom scores of the budesonide-treated group reached statistical significance within 36 hours compared with placebo (P = .01); in those patients treated with fluticasone, significant improvement compared with placebo was first observed within 60 hours. Adverse events were mild and transient. Conclusions: Once daily budesonide aqueous nasal spray, 256 μg, was significantly better in controlling the symptoms of perrenial allergic rhinitis than once daily fluticasone propionate, 200 μg, especially nasal blockage. Both treatments were superior to placebo. Budesonide may have a faster onset of action than fluticasone. (J Allergy Clin Immunol 1998;102:902-8.)     

Allergic fungal sinusitis due to Curvularia lunata

The clinical and pathologic features of allergic fungal sinusitis caused by Curvularia lunata, as seen in two patients, are described. The findings are identical to those of allergic aspergillus sinusitis. Patients have allergies, nasal polyposis, and, occasionally, eosinophilia. Radiographs show opacification of multiple sinuses without bone destruction. Surgical specimens consist of polyps and inspissated, mucoid material. Diagnostic microscopic features, termed "allergic mucin," include eosinophils, numerous Charcot-Leyden crystals, and hyphae embedded in pools of mucus. The recognition of allergic mucin may be impeded by extensive degranulation and fragmentation of the eosinophils. In addition, the fragments of mucin exhibit large, poorly stained central areas, probably due to incomplete penetration by the fixative. Eosinophils are easier to recognize in well-fixed areas. Electron microscopy, though not of diagnostic necessity, confirms the eosinophilic nature of the infiltrate. It is important that surgical pathologists recognize this distinctive clinicopathologic entity and recommend appropriate cultures.     

A familial predisposition in bronchial hyperresponsiveness among patients with allergic rhinitis

Background: Nonasthmatic subjects with allergic rhinitis often have bronchial hyperresponsiveness (BHR). The mechanisms responsible for BHR in asthma include genetic predisposition and airway inflammation, but the causes of BHR in allergic rhinitis are poorly understood. Objective: The aim of this study was to investigate whether there is a familial predisposition in allergic rhinitis–associated BHR. Methods: One hundred fifteen children with allergic rhinitis (probands) and their family members underwent methacholine bronchial challenge and skin prick tests with airborne allergens. The probands were divided into 2 groups: BHR(+) (methacholine PC₂₀ <18 mg/mL determined by the dosimeter method; n = 42) and BHR(–) (n = 73). Results: The overall prevalence of BHR was higher in family members of BHR(+) probands than in those of BHR(–) probands (23.3% [27 of 116] vs 10.5% [21 of 200], P < .01). In mothers, this difference was marked (21.4% vs 8.2%, P < .05); a similar trend was observed in fathers (16.7% vs 6.8%) and siblings (34.4% vs 18.5%), although the differences did not reach significance (.05 < P < .1). The bronchial responsiveness index (BR index), a continuous variable derived from the results of methacholine challenge, was significantly higher among family members of the BHR(+) group than those of the BHR(–) group. Furthermore, even when only family members without BHR were considered, the BR index was significantly higher among those (n = 89) of the BHR(+) group than those (n = 179) of the BHR(–) group. There was no difference in atopic status as assessed by the prevalence of atopy (or atopy index) between family members of the BHR(+) group and the BHR(–) group. Conclusion: Our results indicated that there is a significant familial predisposition for BHR among patients with allergic rhinitis. Further studies are needed to elucidate whether genetic factors play a role in allergic rhinitis–associated BHR. (J Allergy Clin Immunol 1998;102:921-6.)     

Aspergillus fumigatus components distinguish IgE but not IgG4 profiles between fungal sensitization and allergic broncho‐pulmonary aspergillosis

Aspergillus fumigatus is the causative agent of allergic broncho‐pulmonary aspergillosis. Prompt and accurate diagnosis may be difficult to achieve with current clinical and laboratory scores, which do not include immune responses to recombinant A. fumigatus allergens. We measured specific immunoglobulin E and G4 directed to recombinant A. fumigatus allergens in 55 cystic fibrosis patients without allergic broncho‐pulmonary aspergillosis but sensitized to A. fumigatus and in nine patients with allergic broncho‐pulmonary aspergillosis (two with cystic fibrosis and seven with asthma). IgG4 responses to recombinant A. fumigatus allergens were detected in all patients, but neither prevalence nor levels were different between the two patient groups. On the other hand, both prevalence and levels of IgE responses to Asp f 3, Asp f 4, and Asp f 6 helped distinguish allergic broncho‐pulmonary aspergillosis from A. fumigatus sensitization with good negative and positive predictive values.     

A case of allergic fungal sinusitis caused by Bipolaris spicifera]

We describe a case of allergic fungal sinusitis (AFS) caused by Bipolaris spicifera, the first case reported in Japan. A 70-year-old man was admitted to our hospital because of diplopia following bilateral nasal obstruction and discharge. Radiological studies using computed tomographic scan showed a large soft tissue mass occupying the right frontal, bilateral ethmoid and sphenoid sinuses. He underwent drainage surgery and histopathological examination of the contents of the paranasal sinuses revealed scattered fungal hyphae within "allergic mucin". By cytological examination, these hyphae showed septation at irregular intervals, and were swollen to various sizes. Microbiological studies identified the fungus as Bipolaris spicifera. The presence of allergic mucin and scattered fungal hyphae were very important findings in making a diagnosis of AFS histopathologically, so squash cytology of the contents of the paranasal sinuses was quite useful to observe fungal elements and identify the strain in this case.     

Allergic Aspergillus sinusitis: a newly recognized form of sinusitis

The clinical and pathologic features of seven cases of a newly recognized form of chronic sinusitis are described. Most patients were young adults with a history of asthma, and all had chronic nasal polyps. Radiographically, there was opacification of multiple sinuses. Recurrent sinusitis was common, and several patients underwent numerous surgical drainage procedures. Histologically, a distinct mucinous material containing eosinophils, Charcot-Leyden crystals, and fungal hyphae was found in tissue resected from the sinuses. We believe that these findings constitute a distinct clinicopathologic entity that we term allergic Aspergillus sinusitis. This condition shares similar histopathologic features with allergic bronchopulmonary aspergillosis (ABPA) but affects the paranasal sinuses rather than the lung. Implications for therapy of this form of sinusitis and its possible relationship to allergic lung diseases are discussed.     

Curvularia—favorable response to oral itraconazole therapy in two patients with locally invasive phaeohyphomycosis

Curvularia species are ubiquitous and occasionally lead to infections in humans. In immunosuppressed patients, infections are often serious, and systemic dissemination is not uncommon. The optimal antifungal therapy is unclear. I here present two cases, a healthy man with locally invasive, mulicentric paranasal fungal sinusitis, and a case of progressive verrucal distal onychomycosis that developed while the patient was undergoing accelerated chemotherapy for non-Hodgkin's lymphoma. Both patients showed excellent responses to treatment with itraconazole suspension. Oral itraconazole may provide a safe and effective alternative for patients with locally invasive non-disseminated mycoses due to Curvularia species.     

Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis

A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus‐related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%‐10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host‐pathogen interactions in A. fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.