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Med Mycol Case Rep
Med Mycol Case Rep
Medical Mycology Case Reports
2211-7539
Elsevier

S2211-7539(24)00043-5
10.1016/j.mmcr.2024.100669
100669
Case Report
A case of refractory onychomycosis caused by Kloeckera apiculata: Successful treatment with itraconazole
Ehrlich-Fein Samantha S. hfein2000@gmail.com
ab⁎
Patel Samir B. ab
a The Dermatology Group, Mason, OH, 45040, USA
b DermPro Dermatopathology, Mason, OH, 45040, USA
⁎ Corresponding author. The Dermatology Group, Mason, OH, 45040, USA. hfein2000@gmail.com
11 9 2024
12 2024
11 9 2024
46 10066924 7 2024
4 9 2024
10 9 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Here, we present the case of an otherwise healthy patient, without risk factors, who developed a refractory case of onychomycosis caused by Kloeckera apiculata, an uncommon human pathogen. The diagnosis was ultimately confirmed by fungal nail plate culture, histopathology, and PCR. Whereas prior treatments with topical 5 % tavaborole solution, oral terbinafine, and oral fluconazole were ineffective, complete clinical and mycological cure was achieved with a 3-month course of oral itraconazole.

Keywords

Onychomycosis
Dermatology
Kloeckera apiculata
Nail disease
Itraconzaole
Handling Editor: Dr Adilia Warris
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pmc1 Introduction

Onychomycosis is a common fungal infection of the nail unit with a worldwide prevalence of up to 10 % [1]. The infection can be caused by dermatophytes, saprophytic molds, and yeasts [2]. The condition typically presents with progressive thickening and discoloration of one or more affected nails involving the hands, feet, or both. In more than a third of with patients affected with pedal onychomycosis, concomitant cutaneous involvement (tinea pedis) is also present [3].

Kloeckera apiculata is the anamorph of Hanseniaspora uvarum, an ascomycetes yeast originally described in 1870 [4]. It is commonly found in many fruits, soil, coffee, mollusks, and is naturally involved in the fermentation of certain wines, beer, and cider [5,6]. Despite its relative abundance in nature, Kloeckera apiculata is an exceedingly rare cause of human disease and an even rarer cause of onychomycosis, with only 3 previous cases having been reported [[7], [8], [9]]. Given the rarity of this infection, successful treatment options have not been formerly described.

2 Case presentation

On day 0, a 32 year-old white male presented to dermatology clinic for treatment of persistent thickening and discoloration of several toenails and his right thumbnail for the past 3 years (see Figs. 1 A,B). The patient had no significant past medical history and was otherwise in good health. The patient had previously been diagnosed with a “fungal nail infection” by another dermatologist, although no diagnostic testing had been performed. He had initially been treated with topical 5 % tavaborole solution daily for approximately 6 months with minimal improvement. When the topical treatment proved ineffective, the dermatologist subsequently prescribed a 3-month treatment of oral terbinafine, which resulted in only modest, temporary clinical improvement. Eventually several months later, the dermatologist prescribed a third treatment with oral fluconazole, which was similarly ineffectual.Fig. 1 A,B: Onycholysis and subungual debris are present on several affected digits.

Fig. 1

On physical examination, subungual thickening and whitish discoloration was evident on several toenails and the right thumbnail. Cutaneous involvement was not present. In order to establish the diagnosis, samples of nail plate keratin were trimmed from several affected digits and submitted for fungal culture and histopathological analysis. Histologic analysis of the nail plate specimens showed hyperkeratosis, parakeratosis, and multiple PAS-positive, elongated, septate hyphae and blastoconidia (Fig. 2, Fig. 3). Samples of nail plate keratin were also submitted for fungal culture (Labcorp, Burlington, NC). Colonies grown on Sabouraud agar were positive after 1 week of incubation. The colony surface was smooth and the color creamy white. Microscopic examination of the cultured colonies again showed blastoconidia. The culture was initially screened by MALDI-TOF mass spectrometry however the organism in question was not a validated species in the company's proprietary MALDI database at the time.Fig. 2 The nail plate shows hyperkeratosis, parakeratosis, and onycholysis. Hematoxylin & Eosin, original magnification X10.

Fig. 2

Fig. 3 The nail plate show multiple PAS-positive, sphere-shaped conidia (inset red arrow) and elongated hyphae (inset yellow arrow). Periodic acid-Schiff, original magnification X20. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Since the specimen could not be identified with MALDI-TOF MS, it was then sent for definitive PCR sequence analysis using a proprietary set of nuclear ribosomal internal transcribed spacer (ITS) region primers specific for yeasts and molds which confirmed Kloeckera apiculata as the causative agent.

Given the patient's motivation to improve his nail condition and lack of response to multiple prior treatments, an oral course of itraconazole 200 mg daily for 3 months was prescribed on day +30. At the conclusion of the treatment, the patient noted marked improvement in all affected nails. At 6 months post-treatment with itraconazole (day +300), a follow-up fungal nail culture was obtained and was negative for fungal growth. The patient has had no recurrence of his nail condition in over 12 months of observation (day +480).

3 Discussion

The differential diagnosis for nail dystrophy observed in this patient includes inflammatory, infectious, and traumatic etiologies. Common inflammatory causes of nail dystrophy include psoriasis, lichen planus, and atopic dermatitis [10]. Infections of the nail unit are most commonly fungal in origin, although bacterial infections typically from staphylococci do occur [10]. Most cases of onychomycosis are due to dermatophyte infection with Trichophyton rubrum being the predominant pathogen isolated [11]. Non-dermatophyte causes of onychomycosis include molds and yeasts and account for 10–25 % of all cases [11]. In order to differentiate Kloeckera apiculata from other yeasts, molecular techniques such as PCR and MALDI-TOF mass spectroscopy are most frequently employed [12,13].

Currently FDA-approved treatments for onychomycosis are stated for those caused by dermatophyte infection only. Approved topical treatments include ciclopirox, efinaconazole, and tavaborole, while approved oral treatments consist of griseofulvin, terbinafine, and itraconazole [14]. Although not specifically indicated, evidence for the efficacy of itraconazole as a treatment for non-dermatophyte causes of onychomycosis including both yeasts and molds has been previously reported [15].

Of the 3 previous reported cases of onychomycosis caused by Hanseniaspora uvarum, partial “clinical improvement” was observed in a single patient treated with 40 % urea ointment followed by ciclopirox nail lacquer [9]. Neither complete clinical, nor mycological cure for onychomycosis caused by Hanseniaspora uvarum (Kloeckera apiculata) has been previously reported.

In summary, this case documents the fourth occurrence of onychomycosis caused by Kloeckera apiculata and its first-ever successful treatment with oral itraconazole. Given the patient's previous treatment failures and present durable response, oral itraconazole should be considered as first-line treatment for future cases of nail infection caused by Kloeckera apiculata.

CRediT authorship contribution statement

Samantha S. Ehrlich-Fein: Writing – review & editing, Writing – original draft, Formal analysis, Data curation, Conceptualization. Samir B. Patel: Writing – review & editing, Writing – original draft, Supervision, Resources, Methodology, Investigation, Formal analysis, Conceptualization.

Declaration of competing interest

There are none.

Acknowledgements

There are none.
==== Refs
References

1 Westerberg D.P. Voyack M.J. Onychomycosis: current trends in diagnosis and treatment Am. Fam. Physician 88 11 2013 762 770 24364524
2 Leung A.K.C. Lam J.M. Leong K.F. Hon K.L. Barankin B. Leung A.A.M. Onychomycosis: an updated review Recent Pat. Inflamm. Allergy Drug Discov. 14 1 2020 32 45 31738146
3 Lipner R.S. Scher R.K. J. Drugs Dermatol. JDD 14 5 2015 492 494 25942668
4 Reess M. Botanische Untersuchungen über die Alkoholgährungspilze. A. Leipzig 1870 Felix
5 van Wyk N. Badura J. von Wallbrunn C. Pretorius I.S. Exploring future applications of the apiculate yeast Hanseniaspora Crit. Rev. Biotechnol. 44 1 2023 100 119 36823717
6 Albertin W. Setati M.E. Miot-Sertier C. Mostert T.T. Colonna-Ceccaldi B. Coulon J. Hanseniaspora uvarum from winemaking environments show spatial and temporal genetic clustering Front. Microbiol. 6 2016 1569 26834719
7 García-Martos P. Hernández-Molina J.M. Galán F. Ruiz-Henestrosa J.R. García-Agudo R. Palomo M.J. Isolation of Hanseniaspora uvarum (Kloeckera apiculata) in humans Mycopathologia 144 2 1998-1999 73 75
8 Emmanouil-Nikoloussi E. Kanellaki-Kyparissi M. Papavassiliou P. Koliakos K. Dermentzopoulou M. Foroglou C. "Hanseniaspora uvarum" the ultrastructural morphology of a rare ascomycete, isolated from oral thrush Bull Group Int Rech Sci Stomatol Odontol 37 1–2 1994 13 17 7994154
9 Sánchez-Cárdenas C.D. Vega-Sánchez D.C. González-Suárez T.R. Flores-Rivera J. Arenas R.G. Corona T. Onychomycosis caused by Kloeckera apiculata: a case report in a patient with multiple sclerosis Skin Appendage Disord. 8 1 2022 49 52 35118131
10 Lee D.K. Lipner S.R. Optimal diagnosis and management of common nail disorders Ann. Med. 54 1 2022 Dec 694 712 35238267
11 Leung A.K.C. Lam J.M. Leong K.F. Hon K.L. Barankin B. Leung A.A.M. Wong A.H.C. Onychomycosis: an updated review Recent Pat. Inflamm. Allergy Drug Discov. 14 1 2020 32 45 31738146
12 Cadez N. Raspor P. deCock A.W. Boekhout T. Smith M.T. Molecular identification and genetic diversity within species of the genera Hanseniaspora and Kloeckera FEMS Yeast Res. 1 4 2002 279 289 12702331
13 Pinto T.N. Oliveira L.M.A. da Costa G.L. Costa N.S. Francisco E.C. Pinto T.C.A. Oliveira M.M.E. Detection of Hanseniaspora opuntiae in anovaginal samples of pregnant women in Rio de Janeiro, Brazil-a case report Front. Cell. Infect. Microbiol. 30 14 2024 1394663
14 Falotico J.M. Lipner S.R. Updated perspectives on the diagnosis and management of onychomycosis Clin. Cosmet. Invest. Dermatol. 15 2022 1933 1957
15 Del Rosso JQ. Advances in the treatment of superficial fungal infections: focus on onychomycosis and dry tinea pedis J. Am. Osteopath. Assoc. 97 6 1997 339 346 9232944
