PROPOSED RE-CLASSIFICATION OF DISEASE CAUSED BY ASPERGILLUS SPP. INCLUDING DIAGNOSTIC CRITERIA

Hope WW 1 , Walsh TJ 2 , Denning DW 1

Author address: 

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Abstract: 

Disease manifestations associated with Aspergillus spp. are protean and dependent on a complex interaction between fungus and host making the derivation of a satisfactory classification system difficult. Certain aspects of disease associated with Aspergillus such as invasive pulmonary aspergillosis and allergic bronchopulmonary aspergillosis (ABPA) have been rigorously defined but a universally acceptable classification system would be of enormous benefit for clinical trials and would also facilitate comparability between studies. Our proposed reclassification is based upon infectious burden and immune response. In the first category, “high tissue burden”, Aspergillus is directly demonstrable in affected tissue where it causes tissue damage (or its presence inferred in an appropriate setting) using standard techniques (EORTC/MSG criteria CID 2002;34:7-14). This category may be further sub-classified by time course (acute, subacute) and/or according to the affected organ/tissue (disseminated, pulmonary, sinus, central nervous system, osteomyelitis, tracheobronchitis, endocarditis, and inoculation injuries (cutaneous, keratitis, post-operative/traumatic)). This group is characterised by either significant underlying immunological defects, local trauma or a high inoculum which overwhelms the intact immune system. Tissue damage is primarily attributable to Aspergillus itself with angioinvasion and tissue infarction the hallmark, although immune response plays an increasing role in tissue damage in sub-acute disease. The second category, “low tissue burden”, is characterised by the inability to identify Aspergillus hyphae directly in tissue despite progressive tissue damage. The presence of Aspergillus is inferred from data such as positive serology or isolation of Aspergillus from sites other than tissue. Chronic pulmonary aspergillosis is classified here. A definition of this entity has recently been proposed (Denning et al CID in press) which consists of chronic pulmonary symptoms, cavitary pulmonary disease, positive Aspergillus precipitins, elevated inflammatory markers, exclusion of other pathogens and the absence of significant immunocompromise. A sub-classification consisting of cavitary, necrotising and fibrotic variants has also been proposed (Denning et al CID in press). Granulomatous sinusitis and onychomycosis are classified here. The third category is characterised by mucosal colonisation by Aspergillus spp. and either a local inflammatory or allergic response. Inflammatory phenomena include otitis externa, saprophytic maxillary sinusitis, bronchitis and obstructing bronchial aspergillosis. Allergic manifestations include ABPA, extrinsic allergic alveolitis and allergic fungal sinusitis (Greenberger Clin Allergy Immunol 2002;16:449-68). The fourth category, mucosal colonisation, refers to the isolation of Aspergillus on at least one occasion without any evidence of tissue invasion, inflammatory or allergic complication as determined by clinical, radiological or serological investigation. Characteristic clinical, radiological, microbiological, histological and serological manifestations are provided for each category as are standard definitions where they exist.
2003

abstract No: 

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Full conference title: 

The 15 th Congress of the International Society for Human and Animal Mycology
    • ISHAM 15th (2003)