Dermatology Online Journal

Non-dermatophyte mold onychomycosis in Sri Lanka
Ranthilaka R Ranawaka MD¹, Nelun de Silva MD², Ramya W Ragunathan MD¹
Dermatology Online Journal 18 (1): 7

1. Department of Dermatology, Teaching Hospital Karapitiya, Galle, Sri Lanka
2. Department of Microbiology, University of Ruhuna, Galle, Sri Lanka

---

Abstract

Dermatophytic and non-dermatophytic onychomycosis (NDM) was indistinguishable clinically in our case series. Making a clinical diagnosis of onychomycosis without mycology is the routine practice in Sri Lanka. The prevalence of NDM (45.8%) was very high in our patient population, followed by yeasts (34.1%); dermatophyte infection made up only 20%. Therefore, the treatment of onychomycosis with griseofulvin seems futile. Close contact with soil, the habit of walking barefoot, frequent emersion of hands in water, and a hot, humid climate partly explain the variation in causative pathogens in this case series.

---

Clinical cases

Figure 1	Figure 2

Figure 1. 28-year-old farmer complained of black discoloration and painful swollen posterior nail folds of the great toes for 5 years and of the fingers for 3 months. Mixed growth of A. niger and Penicillium sp were isolated. Frequent contact with mud on the bare feet and hands was identified as the predisposing factor.

Figure 2. 35-year-old woman exhibited second and third left toenail onycholysis, subungual hyperkeratosis, and discoloration without paronychia, that evolved over 2 years. Surgical nail avulsion had been performed twice without improvement. Cladosporium sp was isolated. Gardening barefoot and frequent contact with water during household work were identified as possible predisposing factors.

Figure 3	Figure 4

Figure 3. A 24-year-old female medical student presented with bilateral great toenail involvement for 5 years. On examination yellow green discoloration, onycholysis, and subungual hyperkeratosis were noted without paronychia. Surgical nail avulsion had been performed twice without antifungal therapy. Paecilomycis sp was isolated. Except for the barefoot gardening no other predisposing factor was identified in this case.

Figure 4. A 32-year-old woman teacher presented with nail plate thickening, discoloration and painful paronychia on both hands for 2 years duration. Fusarium sp was isolated. Being a diabetic for 1 year and frequent contact with water during household work were identified as predisposing factors. Her diabetes was under control with oral hypoglycemics.

Figure 5	Figure 6

Figure 5. The patient in Figure 4 had total dystrophy of bilateral thumb nails. All affected nails were associated with painful paronychia. Fusarium sp was isolated.

Figure 6. The patient in Figure 4 had DLSO on bilateral great toenails. All affected nails were associated with painful paronychia. Fusarium sp was isolated.

Eighty-four percent of our patients had involvement of their great toes (bilateral- 59, left great toe only-7 and right great toe only-3). Toenails only were involved in 37 percent whereas fingernails only in 12 percent; the thumb nail was the most common. Both toenails and fingernails were involved in 51 percent.

Figure 7	Figure 8

Figure 7. A 57-year-old clerk presented with painful discoloration of the right middle fingernail and bilateral great toenails for 8 months duration. Fusarium sp was isolated. A predisposing factor was not apparent from his history.

Figure 8. The patient in Figure 7 with painful DLSO involving bilateral great toenails for 8 months. Fusarium sp was isolated. The main site of entry by invading organisms in our case series was the distal and lateral margins (DLSO) (76%).

Figure 9

Figure 9. Total dystrophic onychomycosis with paronychia in an immunocompetent patient. Candida albicans was isolated. This nail belonged to a 53-year-old staff nurse, and only the R thumb nail was affected.

In patients with only fingernail involvement, yeasts were the most common pathogens (2 Candida albicans, 5 other Candida sp, 2 A. niger, and 1 A. terreus). Total onychodystrophy was noted in 3.9 percent (n=5).

Methods

The specimens were collected as nail clippings and subungual debris. Nail samples were microscopically studied after clearing for 3-4 hours in 40 percent KOH. For cultures 3-4 nail fragments were inoculated in Sabouraud-Dextrose-agar chloramphenicol-gentamicin medium, with and without cycloheximide. They were incubated at 28-29°C for 3 weeks. Tease mount preparation of the colonies in lactophenol cotton blue were used for generic identification of the fungal isolates. Further testing with slide cultures were done for species identification. All NDM samples were done in duplicate.

Diagnosis of NDM onychomycosis was made on the basis of the following criteria:

• Nail abnormalities consistent with the diagnosis
• Positive KOH preparation with presence of hyphae in the nail keratin
• Growth of the same mold in duplicate cultures
• Failure to isolate a dermatophyte or yeast in culture
• Colony morphology and sporulation pattern

Significant growth was considered when both microscopy of direct mounts in KOH and culture was positive for fungi.

Results

One hundred twenty-eight patients, 97 women and 31 men (3:1 ratio), with clinical onychomycosis were studied. Women were significantly predominant (75.8%); it is possible that men were less likely to seek treatment.

Onychomycosis was uncommon in children; 3 percent in this case series, compared to 88 percent of adults (18-65 years), and 9 percent elderly. The duration of nail dystrophy before presentation ranged from 2 months to 25 years, with the average being 4 years.

The diagnosis of onychomycosis was established in 66.4 percent of the clinically suspected patients; 20 percent of the infections were dermatophytes, 45.8 percent NDM, and 34.1 percent were Candida sp (Table 1).

Discussion

In routine practice we noticed that the prevalence of NDM onychomycosis was much higher in our setting than reported in the literature. This study was conducted in an outpatient skin clinic to assess the prevalence and clinical manifestations of NDM onychomycosis. Patients with nail involvement with some form of morbidity such as pain, embarrassment over fingernail involvement, foul odor with discharging pus, or limitation in work because of pain and burning sensation were the reasons that were stated for presenting for treatment.

There was no significant fungal growth in 33.6 percent of our patients; they may have had nail dystrophy related to frequent minor trauma or had fungi that did not grow in our culture. Repeated laboratory fungal tests could eventually produce positive results in some of these. The patients who were clinically suggestive of onychomycosis were started on antifungal therapy even though the fungal tests were negative in duplicate samples [1].

In our study population, 16.25 percent were farmers and 15 percent were manual laborers who worked in paddy fields (in mud and water) and tea plantations with bare feet or in open rubber slippers. Wearing rubber boots or closed shoes were a rare practice in this group due to hot humid climate and low economy More than half (63%) had a history of frequent contact with water; of these 43 percent were women engaged in household work. In fact, 18 percent denied any predisposing factor. The majority (83%) of our patients were considered to be from the middle socio-economic group .

A. niger, A. flavus, and Fusarium are saprophytic molds, which are widely distributed as soil and plant pathogens [2, 3, 4]. Although NDM and candida can invade healthy nails, secondary colonization of previously damaged nail is common. This explains the striking results we obtained and confirmed, in contrast to studies done in temperate countries. This variation may be explained by (1) geographic differences in mold distribution, (2) differences in the criteria used for diagnosing mold onychomycosis, and (3) use of mycological methods inappropriate for mold growth. High prevalence of NDM onychomycosis has been reported from India (22%) [5] Malaysia (35.5%) [6], Thailand (51.6%) [7] and Pakistan (68%) [8], too.

In temperate zones, the most frequently isolated molds were Aspergillus sp (4% in nails, 3% in skin) and Scopulariopsis brevicaulis (3% in nails, 0.4% in skin) [3]. Aspergillus niger was the most common pathogen (22%) isolated in our study, followed by Aspergillus flavus (6%) and Fusarium sp (6%). Other Candida sp were isolated in 23.5 percent, whereas Trichosporon yeasts (8.2%) and Candida albicans (2.3%) followed (Table 1). Aspergillus niger was the most common pathogen identified in diabetics in our case series (Table 2); increased incidence of Candida or dermatophyte nail infection was not seen among them [9].

Tosti et al [2] reported that the majority (76%) of onychomycosis caused by NDM presents with paronychia. Our data support this by showing concomitant paronychia in 61 percent in the NDM infections and 38 percent in the Candida infections (Table 3).

Dermatophytic and non-dermatophytic onychomycosis were indistinguishable clinically in our case series. The clinical diagnosis of onychomycosis without mycology is routine practice in Sri Lanka. Therefore, because the prevalence of NDM (45.8%) and yeasts (34.1%) were very much higher than dermatophyte infections (20%), treatment of onychomycosis with griseofulvin seems futile [10, 11].

NDM showed a poor response to current topical, oral, or device-related antifungal therapies [12]. In the study conducted by Ranawaka et al [11], with oral itraconazole pulse therapy, even though the mycological cure was 100 percent, Fusarium sp showed only 60-70 percent clinical cure after 12 months follow-up. Gupta AK et al [13] reported that terbinafine gave the highest reported cure rates for the treatment of Scopulariopsis brevicaulis and Aspergillus species infections. A meta-analysis conducted by Yin Z et al [14] showed that the combined risk ratio comparing terbinafine with itraconazole for mycological recurrence rate was 0.44 (95% CI 0.29-0.66), which suggests that itraconazole therapy was more likely to produce mycological recurrence compared with terbinafine therapy. Topical treatment such as ciclopirox nail lacquer may also be effective (data originating from Scopulariopsis brevicaulis and Acremonium species infections), especially when combined with chemical or surgical avulsion of the nail [13, 15]. Total nail avulsion followed by topical antifungal post-operatively was an effective management option (clinical cure rate 88% and mycological cure rate 100%) for patient with single or oligo-onychomycosis [16]. Posaconazole was effective in vitro against Scytalidium dimidiatum. But it showed only partial response in the treatment of superficial scytalidiosis in the clinical trial conducted by Dunad J et al [17]. Three sessions of photodynamic therapy (with methyl-aminolevulinate) separated by 15 days has been used effectively to treat onychomycosis caused by Acremonium sclerotigenum (one case report) [18].

Finally, Amichai B et al [1] showed that, of the 147 cases of clinical onychomycosis initially thought to be negative, 138 (94%) were later found to be positive after up to four consecutive sets of laboratory mycological investigations. Therefore, suggest starting systemic antifungal treatment in patients with suspected fungal infections, even if they have negative laboratory fungal examinations may be useful in some cases.

In conclusion, clinicians must appreciate that the NDM should no longer be disregarded as pure contaminants and choose optimal antifungal agents accordingly.

ACKNOWLEDGEMENT: We thank Mr H K T A Gunasekara, technical officer at the laboratory of the Department of Microbiology, Faculty of Medicine, University of Ruhuna for his hard work during our study.

References

1. Amichai B, Davidovici B, Trau H, Lyakhovitsky A, Grunwald MH, Shemer A. A rationale for systemic treatment in onychomycosis with negative results on fungal examination. Clin Exp Dermatol. 2011 Oct;36(7):724-7. doi: 10.1111/j.1365-2230.2011.04082.x. Epub 2011 May 30. [PubMed]

2. Tosti A, Piraccini BM, Lorenzi S. Onychomycosis caused by non dermatophyte molds: clinical features and response to treatment of 59 cases. J Am Acad Dermatol. 2000 Feb; 42(2pt1):217-224. [PubMed]

3. Gianni C, Cerri A, Crosti C. Non-dermatophytic onychomycosis. An underestimated entity? A study of 51 cases. Mycoses 2000;43:29-33 [PubMed]

4. Greer DL. Evolving role of non dermatophyte molds in onychomycosis. Int J Dermatol 1995; 34:521-9 [PubMed]

5. Ramani R, Srinivas CR, Ramani A, et al. Molds in onychomycosis. Int J Dermatol 1993; 32: 877-8 [PubMed]

6. Ng KP, Saw TL, Madasamy M et al. Onychomycosis in Malaysia. Mycopathologia 1999;147:29-32 [PubMed]

7. Ungpakorn R, Lahaprathan S, Reangchainam S. Prevalence of foot diseases in outpatients attending the Institute of dermatology, Bangkok, Thailand. Clin Exp Dermatol 2004;29:87-90 [PubMed]

8. Farwa U, Abbasi SA, Mirza IA, Amjad A, Ikram A, Malik N, Hanif F Non-dermatophyte moulds as pathogens of onychomycosis. J Coll Physicians Surg Pak. 2011 Oct;21(10):597-600. [PubMed]

9. Al-Mutairi N, Eassa BI, Al-Rqobah DA: Clinical and mycologic characteristics of onychomycosis in diabetic patients. Acta Dermatovenerol Croat; 2010 Jul;18(2):84-91 [PubMed]

10. Tosti A, Piraccini BM, Lorenzi S, Iorizzo M. Treatment of nondermatophyte mold and Candida onychomycosis. Dermatol Clin. 2003 Jul;21(3):491-7, vii. [PubMed]

11. Ranawaka RR, De Silva N, Ragunathan RW. Onychomycosis caused by Fusarium sp in Sri Lanka: Prevalence, Clinical features and Response to itraconazole pulse therapy in six cases. J Dermatolog Treat. 2008;19(5);308-312 [PubMed]

12. Gupta AK, Uro M, Cooper EA. Onychomycosis therapy: past, present, future. J Drugs Dermatol. 2010 Sep;9(9):1109-13. [PubMed]

13. Gupta AK, Drummond-Main C, Cooper EA, Brintnell W, Piraccini BM, Tosti A. Systematic review of nondermatophyte mold onychomycosis: Diagnosis, clinical types, epidemiology, and treatment. J Am Acad Dermatol. 2011 Aug 3. [Epub ahead of print] [PubMed]

14. Yin Z, Xu J, Luo D. A meta-analysis comparing long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole. J Dermatolog Treat. 2011 Jul 31. [Epub ahead of print] [PubMed]

15. Subissi A, Monti D, Togni G, Mailland F. Ciclopirox: recent nonclinical and clinical data relevant to its use as a topical antimycotic agent. Drugs. 2010 Nov 12;70(16):2133-52. [PubMed]

16. Lai WY, Tang WY, Loo SK, Chan Y. Clinical characteristics and treatment outcomes of patients undergoing nail avulsion surgery for dystrophic nails. Hong Kong Med J. 2011 Apr;17(2):127-31. [PubMed]

17. Dunand J, Viguie C, Paugam A. Intermittent posaconazole regimen to treat superficial Scytalidium dimidiatum infection. Eur J Dermatol. 2010 Sep-Oct;20(5):649-50. Epub 2010 Jul 8. [PubMed]

18. Aspiroz C, Fortuño Cebamanos B, Rezusta A, Paz-Cristóbal P, Domínguez-Luzón F, Gené Díaz J, Gilaberte Y. Photodynamic therapy for onychomycosis. case report and review of the literature. Rev Iberoam Micol. 2011 Oct-Dec;28(4):191-3. Epub 2011 Apr 5. [PubMed]

© 2012 Dermatology Online Journal