Onychomycosis: a critical study of techniques and criteria for confirming the etiologic significance of nondermatophytes.

Nondermatophytic filamentous fungi (NDF) other than Scytalidium species are variously said to cause between 0 and 50% of all toenail onychomycoses, though most estimates are in the 2-5% range. Due to the difficulty of obtaining 'gold standard' control data for comparison, the accuracy of many laboratory evaluation processes used to deal with potential NDF onychomycoses has never been rigorously measured, thus allowing use of differing interpretations of the significance of cultures. To allow valid comparison of these procedures and interpretations, a large series of patients who declined treatment were sampled on multiple occasions from all apparently onychomycotic toenails until adequate certainty had been attained that all etiologic agents had been isolated and, where necessary, confirmed as etiologic via consistent repeated isolation. This information was used to evaluate results that had been obtained in the initial direct microscopy and culture studies for the same patient population, as such results are strongly relied on in routine diagnosis. Direct microscopy (KOH) was found to be 73.8% sensitive for dermatophytes and 67.2% sensitive for proven etiologic NDF (difference not significant). Culture of the initial specimen coincidentally had a sensitivity of 74.6% for both fungal groups. KOH and culture in tandem were 83.9% sensitive for indicating fungal etiology based on the first specimen. Different evaluative frameworks currently used to interpret NDF isolations were contrasted. The 'classic' evaluation procedure, in which all NDF considered etiologic must be isolated from at least two successive nail specimens, at least one of which must be microscopic positive for compatible fungal filaments, had a sensitivity of 59.5% but a specificity of 100% for true NDF infections and mixed NDF/dermatophyte infections. The most widely used 'simple association' evaluation criterion, in which NDF outgrowth is considered etiologic whenever direct microscopy is positive for fungal elements and no dermatophyte grows out from the initial specimen, had a sensitivity of 53.6% and a specificity of 70.3% for NDF infections. A frequently criticized, but in some quarters still advocated, variant of the simple association criterion considers NDF outgrowth to be significant whenever the corresponding specimen is positive for fungal filaments in direct microscopy; application of this criterion yielded a sensitivity of 60.7% for true infections but a specificity of only 42%. With the aid of two standard notes soliciting repeat specimens, the classic criterion was able to attain 92.7% accuracy in recognizing all NDF etiologic agents and 100% accuracy in disregarding all contaminants from initial specimens that were positive in direct microscopy and yielded a filamentous fungus in initial culture. Even in exhaustive longitudinal study, only 20.2% of NDF infections were found to be associated with a concurrent dermatophytosis. In auxiliary studies, some nails remained NDF-infected after dermatophytes had been successfully eliminated by therapy.