FUNGAL RHlNOSINUSITIS: A SPECTRUM OF DISEASE
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UNUSUAL FUNGAL PATHOGENS IN FUNGAL RHINOSINUSITIS Wiley A. Schell, MS
The number of fungal species is estimated to be as many as 1.5 million. Roughly 70,000 of these species have been discovered, and about 500 to 800 more are described each year.23 Of these, approximately 300 have been documented as causing disease in humans and other animals." Certain of these species clearly are more virulent than others and are responsible for disproportionate numbers of infections. Some of the remaining species cause enough morbidity or mortality to be considered emerging pathogens." A full recognition of the medical challenge posed by fungi requires acceptance of the concept that quite a few more than these 300 species probably have the potential to cause disease in humans under favorable circumstances. This presents several problems in medical mycology, two of which are documentation of unusual fungal pathogens and fostering a wider awareness of them. THE PROBLEM OF REPORTING It is the consensus of those engaged in medical mycology that the incidence of mycoses and the recognized diversity of etiologic agents are increasing. Unfortunately, the true incidence and associated human and monetary costs of these infections remain unknown. Currently there is no federal mandate for the reporting of fungal diseases nor has funding been available for voluntary efforts." As a result, one relies mainly on reports in the medical literature to infer conclusions about the relative incidence
From the Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina
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of various pathogenic fungi. Obviously this sometimes leads to incorrect beliefs. For example, species of Aspergillus are frequent causes of sinusitis, and for many years it was assumed that septate hyphae seen during microscopic examination of clinical specimens denoted aspergillosis. Gradually, however, it became clear instead that species of the dematiaceous genera, such as Alternaria, Curoularia, and Bipolaris, when taken as a group are the predominant causes in certain syndromes of rhinosinusitis, and that the hyphae of these species seen in tissue can closely resemble those of Aspergillus species. Such advances in knowledge can be slow to develop and become widely recognized. One explanation for this is that the frequency of case reports of unusual agents often tends to be bimodal. Following the first report of a newly recognized etiologic agent, a second and perhaps third report might follow. Thereafter the use of reporting additional cases is less compelling, both for would-be authors and journal editors, and these experiences frequently go unreported. A second round of publications may follow if individuals encounter several additional cases that permit them to report a small series and perhaps incorporate a review of previous reports. To illustrate, immediately following publication of Nodulisporium species as a cause of sinusitis, a second case was encountered (personal communication, South Carolina Department of Health, 1994) but never has been published. Other examples include at least three cases of sinusitis caused by Schizophyllum commune, and at least two of Scedosporium apiospermum seen at the author's institution that never have been reported. Of the fungi listed in Table 1, some are quite rare as agents of rhinosinusitis and probably will remain so. Others simply are unusual in the main sense. A few, such as Paecilomyces lilacinus, S commune, and certain species of Fusarium, may prove to be numerous enough that they will be excluded in the future. DOCUMENTATION OF FUNGAL ETIOLOGY
Complete documentation of fungal etiology in a given case includes several factors. First, there should be sound evidence that a disease exists. Positive culture results alone usually are not sufficient evidence. As mentioned previously, almost all of these fungi produce airborne spores and most are Widespread in the environment. As a result, many of these species occasionally appear on culture media in the absence of disease. Second, the fungus should be seen in the clinical specimen, and toward this end it is particularly important that a sensitive method of microscopy be used. The morphology of the fungus seen in the clinical speciments) must be compatible with the fungus recovered in culture. Microscopy and culture results initially may be contradictory in some cases, but careful review of both usually permits resolution. The recovered fungus must be identified properly. Fungal identification, even to the genus level, often can be difficult and errors are more likely if an unusual fungus is encountered. Identification to the species
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Table 1. UNUSUAL FUNGAL PATHOGENS IN RHINOSINUSITIS' Fungal Group
Fungust
Syndromes
References
Ascomycetes
Chaetomium globosum
FB?
2
Basidiomycetes
Schizophyllllm commllne
NS AFS
47 13 25 46
CN1
AFS CI
42
AI
38:1:
DicymaampulliJcrn (Ascotricha chartarum) Dissitimurus exedms Exserohilum mcgi/misii Nodulisporium hillllU/eum Phaeoocremoniunl species Scedosporillm apiospermum (Pseudallescherin boydiJ1 Scedosporillln prolificans Scytalidillm dilllidiatllm Scopulariopsis sp. (Microosclls cinerells) Sporothrix schellckii
CI NS CI AFS NS FB,CI
50 49 36 14 30,48 21,52.54
AI,FB NS C AI?
11,55 31 3 1,33
Aspergillus avenacells Aspergillus quadrilineatus (Emericella qlladrilineatn) Aspergillus nidulellus tBmericella nidllians) Aspergi1lus oryme Pusarium species Pusarium proliferatum Fusarium solani Histoplasma capsllintum Microsporlllll ennis Myriodolltillm keratinophi/ulll Paecilomyces species Paecilomyces variotii Paecilomyces IiIncinus Penicillium species Scopumriopsis acremoniulll Scapular/apsis candida
CI AI
37
NS AI,CN! FB AI AI
15,32 10 5,40 4 27 9 6 29 43 51 20,39,44 35 18 26
Yeasts
Candida albicans CryptocoCCIIS neojormans
AI? AI?
19 12
Zygomycetes
Absidill corymbifern Basidiobolus rnnarum Conidiobollls coronatlls§ Conidiobo/lls incongruus Crmninghamelln bertholetine Mucor ramosissimus R1Iizopus microsporus var. rhizopoditormis Saksenaea vasiJormis
AI (RCZJ AI (RCZ)
28 17
Hyphomycetes, dematlaceous
Hyphomycetes, hyaline
FB?, FB AI AI,AI? AI AI AI? NS AFS
AI (RCZJ AI (RCZJ AI (RCZ) AI (RCZ) AI (RCZ)
53
7 34
8 41 24
AFS = allergic fungal sinusitis; AI (RCZ) = acute invasive, rhinocerebral zygomycosis; CI = chronic invasive; CNI - chronic noninvasive; FB = fungus ball; NS - not specified. "Someunique cases were excluded if the identity of the fungus was neither clearly Illustrated nor attributed to a mycology authority. Inclusion of other fungi in this table was based largely on how often species of a given genus are routinely identified. In some instances, specifically identified species have been grouped under their genus name (e.g., Bipo/nris linwaliL'IIsis as Bipolnris species) and arbitrarily excluded from the table as being among the more frequent causes offungal rhinosinusltis. This was not followed for Fusarium species because these species are more unusual causes of rhinosinusitis. tFungi having both sexual and asexual morphs are listed under the asexual name because this morph is the first to arise in culture. U the sexual form is likely to be seen as well, its name is included in parentheses. tSinusitls is inferred from the presence of palate lesions. §Rare in North America; endemic in certain other regions.
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level usually is demanding, and confirmation by a reference laboratory is encouraged. Molecular approaches to the taxonomy of some of these agents has led to proposals for extensive revisions, which present greater challenges to laboratorians, and potential confusion for clinicians. Any culture reports listing the name of a fungal pathogen that may be unfamiliar to physicians should include interpretations, and the laboratory director should contact physicians to discuss potentially significant findings. In some cases, not all criteria for complete documentation of an unusual etiology can be satisfied. The most problematic circumstance is a positive culture finding in conjunction with negative specimen microscopy. It is essential to evaluate mycology culture results carefully and without prejudice. This is because nearly all of the fungi listed (see Table 1) can be encountered as nonsignificant isolates or as outright contaminants, but conversely, these and other moulds can cause rhinosinus disease and must not be dismissed quickly as unimportant findings. Isolation of a mould from an otolarygologic specimen is always suspicious, and any fungus that previously has been documented as a cause of otolaryngologic disease is particularly so. Although as little as a single colony can be significant, evaluation of cultures should include enumeration of colonies, and notation of whether growth is present in more than one culture vessel. Culture media also should be closely examined to determine whether growth has arisen directly from inocula or instead appears to have arisen apart from the inoculation streaks. These observations can be helpful in determining if a mould might be a culture contaminant. PRACTICAL APPLICATIONS
As yet, there are few standard therapies for the treatment of fungal rhinosinusitis. Differences in pathogenicity as well as susceptibility to antifungal drugs, however, are starting to become apparent for various fungal species. Accurate identification is warranted of genus at least, and species when possible, and can play an important role in determining the choice of treatment for a given case. Treatment options for fungal infections as a whole have increased significantly in the last 10 years, and entirely new classes of drugs with novel mechanisms of action currently are in development. Accurate identification of cause is likely to become increasingly important for the assessment of treatment outcomes as these newer antifungal compounds become available to clinicians. Toward these ends, unusual fungi can be deposited free of charge to the American Type Culture Collection (Manassas, VA) for preservation and subsequent distribution to researchers. References 1. Agger WA, Caplan RB, Maki DG: Ocular sporotrichosis mimicking mucormycosis in a diabetic. Ann Ophthalmol10:767, 1978
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