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• W4309407796 abstract "Onychomycosis is a superficial mycotic infection of the nail caused by dermatophytes, non-dermatophyte molds, and yeast and is thought to be the cause of 50% of nail disease.1-3 Of the various diagnostic methods, evaluation of periodic acid–Schiff (PAS)-stained histologic sections is widely recognized as having high sensitivity and specificity, each exceeding 80%.4 Therefore, nail specimens, typically nail clippings, for evaluation for onychomycosis are commonly received by dermatopathologists. Diagnostic, classification, and treatment approaches continue to evolve as new information is added to the literature to improve our understanding of this infection. Recently, a study evaluating PAS-stained sections of nail clippings and postavulsion nail plates proposed a new histopathologic classification system for onychomycosis with the goal of providing guidelines for treatment.5 While this system is not yet routinely utilized in clinical practice, clearly there is interest in the medical community to engage dermatopathologists in characterizing and thus guiding treatment of this infection. The purpose of this study was to histopathologically characterize the anatomic location of fungi in PAS-stained nail unit biopsies of onychomycosis as opposed to nail clippings. Unlike nail clippings, nail biopsies are oriented and include associated epithelium and onychodermis making them optimal for characterizing the depth and extent of fungal infection in the nail unit. In this retrospective case series, charts of patients with a histopathologic diagnosis of “onychomycosis” were reviewed from a single academic center from May 8, 2012 (inception of our nail clinic) to December 31, 2021. IRB waiver from our institution was obtained. Patients with onychomycosis histopathologically confirmed via evaluation of PAS-stained nail biopsies showing hyphae and/or spores invading any aspect of the nail unit and who had clinical photographs taken at the time of biopsy were included in this study. Nail biopsies were defined as those submitted as such and that histopathologically included nail plate with attached nail bed or matrix epithelium and onychodermis (Figure 1). Patients were excluded if there were no clinical photographs taken at the time of biopsy, if nail plate was not attached to epithelium, or if only nail clippings were submitted for evaluation. Location of onychomycosis was characterized as fungi: (1) within the surface 50% of the nail, (2) within the undersurface 50% of the nail, (3) throughout the full-thickness of the nail, (4) any nail involvement with invasion of nail unit epithelium. Clinical subtype of onychomycosis was characterized as: distal lateral subungual onychomycosis (DLSO), white superficial onychomycosis, proximal subungual onychomycosis (PSO), endonyx onychomycosis (EO), or total dystrophic onychomycosis (TDO).1, 6 Severity of clinical disease was classified as mild (≤25% nail affected), mild to moderate (26%–50%), moderate to severe (51%–74% nail affected), or severe (≥75% nail affected). Among the 19 patients included in this study, all were biopsied to rule out neoplasm in the setting of at least one prior nail clipping negative by PAS for onychomycosis. Fifteen of the patients had fingernail involvement and four had great toenail involvement. Seven (37%), eight (42%), four (21%), zero (0%), and zero (0%) patients had DLSO, TDO, PSO, EO, or SWO, respectively (Table 1). One of the seven patients with DLSO was excluded because of inability to classify fungal location as a result of a detached and therefore unoriented nail plate. Location of fungi within the nail plate in various onychomycosis subtypes and relationship to disease severity of the remaining 18 patients are detailed in Table 1. There was no malignancy nor other neoplasm in any of the specimens. In our study, we have shown in each clinical subtype and clinical severity the lack of consistency in the location of fungi. For example, in two of five (40%) cases of clinically mild onychomycosis there was full-thickness involvement by fungus. And in those with clinically severe onychomycosis there was essentially equal distribution between those in which fungus affected the entire thickness of the nail plate, the undersurface 50%, and the surface 50%. In addition, we found that fungi are within nail keratin and do not invade epithelium or deeper tissue. Limitations of this study include the small sample size, single institution, absence of culture and molecular data limiting the precise subtype of the fungal infection and the small size of nail biopsies. Small nail biopsies carry the inherent risk that they are not representative of the distribution throughout the infected nail. In addition, because we did not perform fungal culture nor molecular diagnostics, we did not characterize Candida onychomycosis. Our findings are important because they help guide clinicians to submit for diagnostic testing and dermatopathologists to evaluate the entire thickness of nail to the surface of nail unit epithelium where we have shown that fungi may preferentially be present. In terms of specimen submission when onychomycosis is in question, it is routine in our practice to first attempt to make the diagnosis by using a dual action nail nipper to painlessly remove as much nail plate as possible and submit it for PAS. If our clinical suspicion for onychomycosis is high and/or if nail plate fragments were obtained elsewhere then we let the nail(s) grow out until an adequate nail clipping can be obtained and perform clipping a second time. However, in some cases no cause for a patient's onychodystrophy can be identified either in nail plate fragments or clinically and biopsy is therefore warranted. In these cases, we take the biopsy from the abnormal nail matrix and/or bed and an edge of that zone. Awareness of the histopathologic distribution of fungi should also enable clinicians and patients to target treatment.6-9 For example, based on our histopathologic findings and clinical correlates, in DLSO where hyphae are more typically located on the undersurface 50% or full-thickness, topical solutions that do not penetrate the plate should be applied to the hyponychium, undersurface of the plate, and the surface nail unit epithelium. The variable histologic location of dermatophytes may help explain variability in expected treatment outcomes based on clinical subtypes alone. Studies with larger numbers of patients are needed to confirm and expand upon these findings as well as their clinical significance to treatment outcomes. Molly A. Hinshaw is tri-founder and part owner of Accure Medical LLC. Kristen Chen MD has no potential conflict of interest relevant to this manuscript. The data that support the findings of this study are available from the corresponding author upon reasonable request." @default.
• W4309407796 created "2022-11-27" @default.
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• W4309407796 date "2022-12-07" @default.
• W4309407796 modified "2023-09-26" @default.
• W4309407796 title "Histopathologic characterization of onychomycosis in nail biopsies: A retrospective case series of 19 patients" @default.
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• W4309407796 doi "https://doi.org/10.1111/cup.14363" @default.
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