Mycopathologia (2008) 166:41–45 DOI 10.1007/s11046-008-9112-5

Onychomycosis Incidence in Type 2 Diabetes Mellitus Patients

Patricia Manzano-Gayosso Æ Francisca Herna´ndez-Herna´ndez Æ Luis Javier Me´ndez-Tovar Æ Yanni Palacios-Morales Æ Erika Co´rdova-Martı´nez Æ Elva Baza´n-Mora Æ Rube´nLo´pez-Martinez

Received: 26 July 2007 / Accepted: 11 March 2008 / Published online: 29 March 2008 Ó Springer Science+Business Media B.V. 2008

Abstract The incidence was deter- rubrum being the first species (37.1%). All these strains mined in 250 type 2 diabetes mellitus (T2DM) patients corresponded to two morphological varieties: who were registered at the Internal Medicine Service ‘‘yellow’’ and typical downy. From the -like from a Mexico city General Hospital throughout a year isolates, 12 corresponded to Candida spp., firstly (January–December 2006). Out of the total of studied C. albicans and C. parapsilosis; three to Cryptococcus T2DM patients, 93 (37.2%) showed ungual dystrophy spp. (C. albidus, C. uniguttulatus and C. laurentii); two and from these, in 75.3% a fungal etiology was asahii; and only one to Pichia ohmeri. corroborated. Out of 70 patients, 34 were men and 36 Six non-dermatophytic were isolated: two women, with an average of 63.5 years. Correlation keratinophylus, two Scopulariopsis between T2DM evolution time and onychomycosis brevicaulis, one fumigatus, and one was significant (P \ 0.01). Distal-lateral subungual Acremonium sp. The fungal mixture corresponded to and total dystrophic onychomycosis were the most T. mentagrophytes with C. guilliermondii; T. mentag- frequent clinical types (55.1% and 33.7%, respec- rophytes with C. glabrata; T. rubrum with C. glabrata; tively). Fifty-eight fungal isolates were obtained; T. rubrum with P. ohmeri. 48.6% corresponded to , Keywords Candida Á Dermatophytes Á Diabetes mellitus Á Onychomycosis P. Manzano-Gayosso (&) Á F. Herna´ndez-Herna´ndez Á E. Co´rdova-Martı´nez Á E. Baza´n-Mora Á R. Lo´pez-Martinez Laboratorio de Micologı´aMe´dica, Departamento de Introduction Microbiologı´a y Parasitologı´a, Facultad de Medicina, UNAM, Ciudad Universitaria, Mexico, CP 04510, DF, Mexico Onychomycosis are common diseases within the e-mail: [email protected] general population, where these represent from 18% to 40% of diseases [1]. However, in adults over L. J. Me´ndez-Tovar 60 years old the disease is 40% more frequent [2] and Unidad de Investigacio´nMe´dica en Dermatologı´ay Micologı´a ‘‘Dr. Ernesto Macotela’’, Hospital de in type 2 diabetes mellitus (T2DM) patients it increases Especialidades, Centro Me´dico Nacional Siglo XXI, 2.5 times [3]. In these patients onychomycosis diag- IMSS, Mexico, DF, Mexico nosis is overestimated since this population commonly presents ungual dystrophy related with the elderly and Y. Palacios-Morales Servicio de Medicina Interna, Hospital General Dr. some diabetes complications such as peripheral vas- ‘‘Darı´o Ferna´ndez Fierro’’, ISSSTE, Mexico, DF, Mexico cular disease and neuropathy [4]. According to Gupta 123 42 Mycopathologia (2008) 166:41–45 et al. [3] 33% of diabetic patients present onychomy- December 2006) were studied. The following data cosis frequently associated with tinea pedis. Lo´pez- were obtained from each patient: gender, age, occu- Gonza´lez and Mayorga [5] found similar data. pation, T2DM evolution time and complications; Among the fungi causing onychomycosis, derma- onychomycosis clinical types and evolution time; tophytes are the most frequent (38–80% of cases), cutaneous lesions suggestive of fungal infection, and followed by (10–24%) and non-dermatophytic previous antifungal treatment. molds (8–14%) [6–8]. is the most common isolated species followed by T. ment- Fungal Cultures agrophytes (20%). On the other hand, A´ lvarez et al. [6] found that from 299 onychomycosis patients, Candida In the patients with any kind of ungual dystrophy albicans was the number one etiological agent fol- (onycholysis, , or pachyonychia), a myco- lowed by T. rubrum. Among the non-dermatophytic logical study was performed. Nail scrapings were molds, was the most prevalent. taken in three consecutive days and microscopically Four onychomycosis clinical types have been examined after 15% potassium hydroxide treatment; described: distal-lateral subungual (D-LSO), proxi- samples were inoculated in ten different points on mal subungual (PSO), white superficial (WSO) and Sabouraud dextrose agar plates with and without total dystrophic (TDO) onychomycosis. The first antibiotics (Bioxon). The cultures were incubated at clinical type is the most common and the last one 28°C and examined daily for 15 days. seems to be a mixture of all the other onychomycosis types [9, 10]. In diabetic patients another clinical Identification of Dermatophytes and Other form has been described, and is named Candida Keratinophilic Fungi onychomycosis characterized by paronychia [11]. In Mexico, as in other countries, diabetes is a great Identification of isolated fungi was based on morpho- public health problem and according to the national logical characteristics and some physiological tests chronic disease survey reported by Membren˜o et al. depending on and species. Dermatophytes and [12], the prevalence of diabetes mellitus is 7.2% in other keratinophilic fungi were grown on bromcresol general population and, T2DM corresponds to 90% of purple milk solids glucose agar, on lactrimel agar, 1% the cases. This disease is the first cause of hospital peptone agar, Christensen-urea agar, 5% NaCl agar; admission. In spite of the fact that other authors have perforation test was also performed [13]. not found a significant difference between onychomy- cosis incidence in the general population and diabetic Identification of Yeasts patients, the latter frequently show vascular and sensibility disorders, resulting in small traumatic Yeast species were identified by using germ tube lesions which represent the access for bacteria and production, morphology on cornmeal agar, colonial fungi infections. pigmentation on chromogenic medium (CHROMagar We conducted a descriptive and observational Candida)[14], Christensen-urea agar and Staib agar, study aiming to determine the onychomycosis inci- and the assimilation of carbohydrates by commercial dence, evolution time, clinical forms, and etiological identification systems (API 20C AUX (bioMeriux) and agents in T2DM patients. YBC card (Vitek)). Isolates identified as C. albicans were studied by means of other tests such as chlamydo- conidia production on three media (Staib [15], casein Materials and Methods [16], and tobacco agar [17]) and growth at 45°C[18]to differentiate it from C. dubliniensis. Patients The Pearson Test (SSPS Program, version 12) was applied when it was necessary to establish compar- Two hundred and fifty T2DM patients admitted in isons. Values of P B 0.05 were considered to be the Department of Internal Medicine at the General significant. Percentages of different factors (gender, Hospital ‘‘Dr. Darı´o Ferna´ndez Fierro’’ ISSSTE, clinical types, etiological agents versus T2DM) in in Mexico city, during a 1-year period (January– patients were also obtained. 123 Mycopathologia (2008) 166:41–45 43

Results Table 2 Onychomycosis clinical types observed in 70 T2DM patients From the 250 T2DM patients, 93 (37.2%) presented Clinical type Toenails Fingernails Total Percentage ungual dystrophy. Seventy patients (75.3%) had onychomycosis confirmed by three different positive D-LSO 29 5 34 48.6 samples for direct examination and culture of nail TDO 19 3 22 31.4 scrapings. Among 70 patients, 34 were males and 36 PSO 6 3 9 12.9 females. The average age was 63.5 years. From 70 WSO 2 3 5 7.1 T2DM patients, 28 presented onychomycosis associ- D-LSO, distal-lateral subungual onychomycosis; PSO, ated with other medical conditions, such as peripheral proximal subungual onychomycosis; WSO, white superficial vascular disease (13), diabetic dermatopathy (six), onychomycosis; TDO, total dystrophic onychomycosis (five), ‘‘diabetic foot’’ (three), and periph- eral neuropathy (one). Concerning the relationship between the T2DM evolution time and onychomycosis, in most of the cases the last started after the diabetes was diagnosed, and this event was statistically significant (P \ 0.01) (Table 1). The clinical localization of onychomycosis in the 70 patients was in toenails (56) and in fingernails (11). Infections of both fingernails and toenails were observed in three cases. Table 2 shows the observed clinical types of onychomycosis, predominating both D-LSO (48.6%) and TDO (31.4%). Figure 1 shows a case of white superficial onychomycosis. Twenty seven patients had associated tinea pedis, two had tinea mannum, and one . Out of the 70 onychomycosis-T2DM patients, 58 fungal isolates were obtained (82.8%): 34 dermato- phytes (48.6%), 18 yeasts (25.6%), and six other non- Fig. 1 A white superficial onychomycosis case caused by dermatophytic molds (8.6%); in four cases a mixture T. rubrum, in a 68-year-old male patient, with an evolution of of two species was found. 7 years. Lesion consists of transverse leuconychia with a single Table 3 shows the different isolated species corre- band lated with the onychomycosis clinical types previously mentioned. Out of the 34 -positive cul- Other yeast-like isolates corresponded to genera tures, T. rubrum was predominant (37%), corresponding Cryptococcus, Trichosporon,andPichia.Fourmixed only to two morphological varieties: ‘‘yellow’’ and fungal species were also observed: two T. rubrum with typical downy. This dermatophyte was the only species C. glabrata;oneT. mentagrophytes with C. guillier- inducing all the onychomycosis clinical types. The mondii; and one T. rubrum with P. ohmeri.Noneofthe yeast-like isolates of the genus Candida were identified isolates firstly identified as C. albicans was differenti- as C. albicans and C. parapsilosis in similar number. ated as C. dubliniensis.

Table 1 Correlation between T2DM and onychomycosis evolution time in 70 hospitalized patients Discussion T2DM (years) Onychomycosis (years) Onychomycosis is a public health problem in patients Range 1–40 1–40 over 60 years old, whose incidence is considered Average 13.5* 10* between 40% and 60% [2, 3, 19], and this is increased * P \ 0.01 with age. According to some authors, onychomycosis 123 44 Mycopathologia (2008) 166:41–45

Table 3 Isolates obtained Fungi Isolates Percentage Clinical types from 70 onychomycosis and T2DM patients correlated TDO DLSO PSO WSO with clinical types Dermatophytes Trichophyton rubrum 26 37.0 11 10 2 3 Trichophyton mentagrophytes 3 4.3 2 – – 1 3 4.3 1 2 – – Epidermophyton floccosum 2 2.9 – 2 – – Subtotal 34 58.6 14 14 2 4 Yeasts 3 4.3 1 1 1 – Candida parapsilosis 3 4.3 1 1 1 – Candida guilliermondii 2 2.9 1 – 1 – 2 2.9 1 1 – – Candida lipolytica 1 1.4 – 1 – – Candida zeylanoides 1 1.4 – – 1 – Pichia ohmeri 1 1.4 – 1 – – Cryptococcus albidus 1 1.4 – 1 – – Cryptococcus uniguttulatus 1 1.4 1 – – – Cryptococcus laurentii 1 1.4 – 1 – – Trichosporon asahii 2 2.9 1 1 – – Subtotal 18 31.0 6 8 4 – Non dermatophytic molds Chrysosporium keratinophilus 2 2.9 – 2 – – Scopulariopsis brevicaulis 2 2.9 1 – – 1 Aspergillus fumigatus 1 1.4 – 1 – – Acremonium spp. 1 1.4 1 – – – Subtotal 6 10.4 2 3 – 1 Total 58 82.8 22 25 6 5 is more frequent in diabetic patients than in general In contrast to other works [3, 22, 23] the T2DM population, especially in those suffering from sensi- patient onychomycosis in our study was predominant bility disorders in soles, in toes, and in nails, in toenails and the distribution was similar in both conditions that could induce pressure necrosis of female and male genders. the skin by constrictive footwear [20, 21]. Gupta As in other studies, the predominant onychomy- et al. [3] reported that a third part of the diabetic cosis clinical types were D-LSO (48.6%) and TDO patients with pachyonychia presented onychomyco- (31.4%) [9, 10, 24]. Without considering the etiolog- sis. However it is not well defined whether this ical agent, in most cases the clinical features were onychomycosis is more frequent in diabetic patients similar. than in general population. In our work, as well as in others, dermatophytes In the present study the onychomycosis incidence were the most frequent agents (48.6%), T. rubrum was 28% in T2DM patients, similar to that reported being the first one followed by Candida spp. [11, 20]. by other authors [3, 5, 22]. In other works, it seems In some studies, Candida spp. are the most frequent that in these patients the T2DM was not the only risk onychomycosis causal agents in T2DM patients. 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