Onychomycosis caused by Pichia guilliermondii: A case report and mini-review.

Onychomycosis has been reported to be mainly caused by dermatophytes. Recently, more attention has been paid to yeast for its increasing morbidity, especially the candida specices. Here we reported a fingernail infection caused by Pichia guilliermondii, the sexual reproduction period of Candida guilliermondii. Itraconazole was used for three courses, and the patient achieved improvement without any significant side-effects. This might be the first onychomycosis case of Candida guilliermondii.

Introduction

Onychomycosis, accounting for approximately 50% of the nail diseases, is a common chronic fungal infection of the nail plate or nail bed caused by dermatophytes, yeasts, and nondermatophyte molds (NDMs) [1]. With healthy nail appearance becoming more and more important for social reasons, increasing attention is paid to the treatment of onychomycosis [2].

While the incidence of onychomycosis keeps growing up and the worldwide prevalence shows 5.5%, dermatophytes, particularly Trichophyton rubrum, are still responsible for the most of fungal nail infection [2]. Among patients with onychomycosis in Dakar, to our surprise, yeasts can be as high as 68.4%–75% of the isolates [3,4]. In spite of C.albicans, non-C.albicans candida species such as C.tropicalis, C.parapsilosis and others were also reported sharing 40% of the fingernail onychomycosis.

C.guilliermondii is a normal component of human microbes on skin and mucous membranes, conditionally causing infection, especially among immunodeficient people [5]. C.guilliermondii onycomycosis is reported for the first time; in addition, the patient is an immunocompetent person.

Case

A 50-year-old healthy male farmer showed up in our clinic on day −7, several fingernails of whose left hand turned yellow and thickened in one year without any symptom. He denied any hand trauma or glucocorticoid using. In general, his left thumb, middle finger and little finger appeared as the type of distal and lateral subungual onychomycosis (DLSO) with crumbed nail plate, yellowish, brownish, partially thickened and friable; while the forefinger showed proximal subungual onychomycosis (PSO) with slight indentations (Fig. 1a).

Fig. 1

General appearance of patient hands (a)exhibiting the thumb, middle finger and little finger of left hand showing DLSO marked with coarse arrows, as well as the forefinger showing PSO marked with thin arrow, (b)exhibiting significant improvements.

Scales of the nail lesion were collected and then observed directly under the microscopy, presenting plenty of spores (Fig. 2). The result of culture turned out with yeast-like colonies as white and smooth as cheese, illustrating the characteristic morphophysiological features of candida species (Fig. 3). rRNA gene sequence analysis after PCR using the universal primer internal transcribed spacer (ITS1/ITS4) confirmed that it had 99.67% homology with that of Pichia guilliermondii (Meyerozyma guilliermondii) (GenBank Accession No. MN473285.1).

Fig. 2

Direct microscopy of C.guilliermondii presenting plenty of spores (40 × ).

Fig. 3

Fungal culture turning out with yeast-like colonies as white and smooth as cheese.

Considering all of the clinical characters and experimental results, the patient was diagnosed as C.guilliermondii onychomycosis. Antifungal therapy was started on day 0 with oral itraconazole in doses of 200mg twice daily and finished on day +7 as the first treatment course. The same dosage of the second course and the third course, respectively, from day +28 to day +35 and day +56 to day +63. At his first follow-up on day +28, the nail lesions improved significantly (Fig. 1b). The patient reported cured in a telephone follow-up on day +6 months, but regretfully, haven't provided with any picture.

This case promoted us to analyze the epidemiology of onychomycosis in China. We searched the database in CNKI(www.cnki.net/), WANFANG DATA (www.wanfangdata.com.cn/) and VIP(www.cqvip.com/)for analyzing the human cohorts of onychomycosis of the last 20 years (see Table 1). All the data we have collected and analyzed is presented in the supplement with references. Comparisons among the proportions of species have been made within different periods and different provinces (see detail in supplement). The comparison came out with more yeast while less dermatophyte cases happening than before (Fig. 4), especially in Jiangsu Province and Guangdong Province (Fig. 5).

Table 1

Characteristics of the included studies in China.

No	Years	Province	Age groups	Most common age group	Diagnosis methods	Confirmed cases	Gender	Etiologic agents (%)				Predominant spp	Notes	Ref
								Yeast	Dermatop-hyte	NDM	Mixed infection
1	2006/05–2010/12	Beijing	3–75yrs	NA	S + DM + C	1229	F = 803, M = 426	188/591	311/591	92/591		T.rub, C.krusei, Aspergillus spp
2	2007/02–2010/02	Hunan	6–72yrs	NA	S + DM + C	305	F = 173, M = 132	106/267	143/267	18/267		T.rub, C.glabrata, C.albicans		[12]
3	2007/04–2008/04	Shandong	5–79yrs	NA	S + DM + C	613	F = 385, M = 228	75/481	386/481	20/481	11/481	T.rub, T.menta, C.albicans		(13)
4	2008/06–2012/11	Guangdong	NA	20–39yrs	S + DM + C	805	F = 444, M = 361	407/805	385/805	13/805		T.rub, T.menta, C.glabrata		(27)
5	2008/12–2010/12	Beijing	5–89yrs	>25yrs	S + DM + C	637	F = 265, M = 372	119/637	442/637	76/637		T.rub, C.albicans, T.menta		(17)
6	2009/07–2010/10	Guangdong	6–96yrs	NA	S + DM + C	196	F = 120, M = 140	70/206	124/206	10/206	2/206	T.rub, C.albicans, T.vio		[9]
7	2010/01–2013/12	Zhejiang	12–73yrs	36–50yrs	S + DM + C	901	F = 516, M = 385	141/468	275/468	52/468		T.rub, T.menta, C.albicans		(19)
8	2010/07–2012/07	Shandong	8–83yrs	NA	S + DM + C	361	F = 212, M = 149	25/239	202/239	5/239		T.rub, C.albicans, T.menta		(28)
9	2010/08–2011/08	Guangdong	6mon-75yrs	NA	S + DM + C	657	F = 271, M = 386	124/231	95/231	12/231		C.albicans, T.rub, C.parapsilosis		(15)
10	2010/12–2011/12	Jiangsu	3–89yrs	20–29yrs	S + DM + C	328	F = 134, M = 194	22/196	162/196	12/196		T.rub, T.menta, C.albicans		(16)
11	2011/01–2011/12	Jiangsu	9–80yrs	NA	S + DM + C	800	F = 390, M = 410	94/800	664/800	42/800		T.rub, Candida spp, T.menta		[11]
12	2011/01–2011/12	Hebei	2–79yrs	NA	S + DM + C	106	F = 76, M = 30	34/111	72/111	5/111		T.rub, T.menta, C.albicans		(14)
13	2011/08–2017/06	Guangdong	NA	20–40yrs	S + DM + C	1162	F = 712, M = 450	359/1162	750/1162	36/1162	17/1162	T.rub, Candida spp, T.inter		(29)
14	2011/11–2012/05	Jiangsu	3–83yrs	21–30yrs	S + DM + C	127	F = 67, M = 60	81/127	10/127	36/127		T.rub, T.menta, Candida spp		(30)
15	2012/02–2016/03	Guangdong	3–92yrs	NA	S + DM + C	421	F = 235, M = 186	176/278	91/278	11/278		T.rub, C.albicans, C.parapsilosis		(18)
16	2012/03–2014/03	Tianjing	1–95yrs	NA	S + DM + C	4100	F = 2265, M = 1835	1309/4625	2998/4625	318/4625		T.rub, C.albicans, T.menta		(31)
17	2012/10–2013/12	Jiangsu	1–85yrs	21–30yrs	S + DM + C	393	F = 238, M = 155	75/393	295/393	23/393		NA		(21)
18	2017/01–2017/12	Hubei	1–81yrs	19–37yrs	S + DM + C	959	F = 587, M = 372	92/959	820/959	47/959		T.rub, Candida spp, T.menta		(20)
19	2010/01–2014/02	Fujian	0–12yrs	10–12yrs	S + DM + C	112	F = 48, M = 64	11/90	73/90	3/90		T.rub, T.menta, C.albicans	Children	(32)
20	2010/06–2015/06	Hubei	10mon-6yrs	3–6yrs	S + DM + C	49	F = 22, M = 27	30/49	17/49	2/49		C.glabrata, T.rub, C.parasilosis	Children	(33)
21	2011/10–2012/10	Shanghai	6mon-14yrs	5–9yrs	S + DM + C	33	F = 12, M = 21	10/33	21/33	1/33		T.rub, C.albicans, C.parapsilosis	Children	(34)
22	2011/04–2013/04	Guangdong	60–82yrs	NA	S + DM + C	107	F = 49, M = 58	31/121	86/121	4/121		T.rub, T.menta, C.albicans	Elderly	(35)
23	2013/01–2014/08	Shanxi	31–84yrs	55–65yrs	S + DM + C + sequencing	153	F = 452, M = 673	27/108	77/108	4/108		T.rub, C.albicans, T.menta	DM	(36)

S: sampling; DM: direct microscopy; C: culture; NA: not available; NDM: nondermatophyte molds; T.rub: Trichophyton rubrum; T.menta: Trichophyton mentagrophytes; C.alb: Candida albicans; C.parap: Candida parapsilosis; C.glab: Candida glabrata; T.inter: Candida interdactylis, T.rub: Candida, T.schoe: Candida; T.vio: Trichophyton violaceum; M.gypseum: Microsporum gypseum; C.tropic: Candida tropicalis.

Fig. 4

Comparison of epidemiology of onychomycosis between two 5 years showing more yeast cases and less dermatophytes ones in latest studies.

Fig. 5

Comparison of epidemiology of onychomycosis in two different times in (a)Jiangsu and (b)Guangdong showing more yeast cases and less dermatophytes ones in the latest study.

Discussion

Although majority of the former studies declared dermatophytes to be the predominant pathogens, different sounds appear in etiology recently. We did a partial analysis of the epidemiology in Iran [6], grouping them into two periods with one from 2000 to 2007 and the other from 2007 to 2015, finding that dermatophytes decreased significantly during years while NDMs increased instead (Fig. 6). Meanwhile, a novel systematic review and meta-analysis in Iran has demonstrated that yeasts are the predominant etiologic agents in 17 studies (70.8%) while dermatophytes in 5 studies (20.9%) [6], similar to the findings in Colombia [7] and Italy [8]. The epidemiology of onychomycosis in China has also shown changes for many years (see the supplements), as the number of yeast cases increased in recent years. Since the epidemiology of onychomycosis has changed and the yeast proportion has increased, more attention should be paid on yeast onychomycosis, especially the most important candida ones.

Fig. 6

Comparison of epidemiology of onychomycosis in two different times in Iran showing more NDMs cases and less dermatophytes ones in the latest study.

Pichia guilliermondii is the sexual reproduction period of C. guilliermondii, with another name of Meyerozyma guilliermondii, inducing infections as opportunistic pathogens particularly in immunocompromised patients. Pichia guilliermondii has been rarely reported, one pulmonary nodules [9] and few candidemia [10], and the patients infected are often accompanied by type 2 diabetes and those who receiving total parenteral nutrition. Our report might be the first time to present such a particular onychomycosis case of C. guilliermondii.

In literatures, the recommending oral medications for onychomycosis includes terbinafine, itraconazole and fluconazole. The guidelines of onychomycosis in China [11] and Britain [12] share similar tips that terbinafine and itraconazole are the first-line medication compared to fluconazole. Terbinafine is found to have more effects on dermatophytes onychomycosis with the clearance up to 70%, while itraconazole shows more effective in yeasts infection.

According to the guidelines and our clinical experience, itraconazole shows more significant efficiency than terbinafine in the treatment of candida infections. As a result, we chose oral itraconazole therapy for this patient which finally worked. Unfortunately, drug sensitive test hadn't been adopted to achieve the most appropriate drug and make a further verification here.

Different from the former cases, we found our patient healthy without personal or family history of diabetes or immunosuppressive therapy, indicating the significance in the further study of species epidemiology and the development of a rapid, accurate and convenient diagnosis of fungal infections in clinic. The low-morbidity species of candida onychomycosis leaves unspecific antifungal therapy, though, empirical therapy before the result of drug sensitive test comes out is of great importance.

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Declaration of competing interest

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