Onychomycosis due to Aspergillus species

Read the full review: Bongomin et al (2017) A Review of Onychomycosis Due to Aspergillus Species. Mycopathologia. https://doi.org/10.1007/s11046-017-0222-9

To make a diagnosis of Aspergillus onychomycosis, the following are required:

-  Positive detection by direct microscopy

-  Either a repeated culture, or molecular detection of Aspergillus spp. (provided no dermatophyte is isolated)

Aspergillus spp. are emerging causative agents of non-dermatophyte mould onychomycosis (NDMO). Proper clinical diagnosis, laboratory workup, and adequate antifungal therapy are the standard of care for all forms of aspergillosis.


A. niger complex, A. flavus complex and A. terreus complex are the most common etiologic Aspergillus species; other rare and emerging species described include A. tubingensis, A. sydowii, A. alliaceus, A. candidus, A. versicolor, A. unguis, A. persii, A. sclerotiorum, A. uvarum, A. melleus, A. tamari, and A. nomius (English and Atkinson, 1974; Nouripour-Sisakht et al., 2015; Zotti et al., 2015).


A recent review on the epidemiology of onychomycosis due to Aspergillus species has shown that Aspergillus spp. constitutes up to 7.7–100% of the proportion of NDMO and between <1% and 35% of all cases of onychomycosis in the general population and higher among diabetic populations accounting for up to 71% in the elderly (Bonifaz et al., 2007; Gianni and Romano, 2004; Gupta et al., 2007; Hilmioğlu-Polat et al., 2005; Romano et al., 2005). About 10 million cases of onychomycosis are attributable to Aspergillus species.

The affected nail may have been previously subjected to trauma and is most often a toenail; peripheral vascular disease is occasionally implicated. Damage can also be induced by hormonal disturbances (diabetes mellitus, Cushing's syndrome, and hypothyroidism) or by HIV/AIDS immunosuppression or on-going biological (immunosuppressive) therapies (Ogawa et al., 2012). The risk of having Aspergillus onychomycosis among diabetics increases with age and duration of diabetes (Wijesuriya et al., 2015).

Aspergillus onychomycosis is seen more among individuals with occupational exposures such as vegetable vendors (Banu et al., 2013) and among babassu coconut breakers (Nascimento et al., 2014), diabetics, and the elderly (Gupta et al., 2007). Some individuals diagnosed with onychomycosis due to Aspergillus spp. do not have identifiable predisposing conditions/occupational risk factors. In fact, Soltani and colleagues in their study reported that up to 70% of patients with Aspergillus onychomycosis had no predisposing conditions (Soltani et al., 2015). Onychomycosis due to Aspergillus spp. is very uncommon in children (Lange et al., 2006; Romano et al., 2005).


Aspergillus spp. are ubiquitous environmental moulds found in soil, decaying vegetation and water and are not transmitted from person to person (Kwon-Chung and Sugui, 2013). Infection starts under the nail near the hyponychium where spores may have lodged or at the lateral nail folds, or on a diseased nail plate colonised by Aspergillus spp (Moore and Weiss, 1948). Once the fungus starts to grow, the infection spreads back toward the cuticle. It looks much the same as any fungal nail infection, discolouring the nail, causing it to become thick, distorted, and flaky (Zaias et al., 2014) An early experimental study with A. versicolor using healthy nail samples showed that A. versicolor could only grow on the surface of the nail without penetrating the nail plate, an evidence of the non-keratinolytic potentials of the Aspergillus spp. (Richardson, 1997). Aspergillus spp. growing in nature often produce colourful pigments; therefore, an Aspergillus nail infection may well appear greenish, black, brown, or various other shades (Banu et al., 2013). The fungus will not, however, spread to the surrounding skin like some other fungal causes of nail infection (Banu et al., 2013).

Clinical manifestation

Particular features suggestive of Aspergillus infection are a chalky, deep white nail with early involvement of the lamina and painful perionyxis without pus (Gianni and Romano, 2004). The toenails are involved 25 times more frequently than fingernails (Banu, 2013). There are 2 common patterns of disease: destructive and superficial white onychomycosis (SWO)(Onsberg et al., 1978; McAleer, 1981; Piraccini and Tosti, 2004), but lateral and distal onychomycosis may also be seen (Bonifaz et al., 2007). In a systematic review of NDMO, Gupta et al (Gupta et al., 2012) reported that Aspergillus spp. manifests as proximal subungual onychomycosis (PSO) in 37.5% of the cases, distal-lateral subungual onychomycosis (DLSO) in 26.1%, and SWO in 25.5%.

Variations of clinical presentations have been observed among the different Aspergillus spp. For example, a study in India showed A. flavus causing 19.2% of DLSO, 18.8% of total dystrophic onychomycosis (TDO), and 9.1% SWO. In contrast, A. niger was associated with 11.5% of DLSO, 10.1% of TDO, 9.1% of SWO, and 6.3% of mixed pattern onychomycosis (MPO), whereas A. fumigatus was associated with DLSO in 2% of the patients, 5.8% TDO and 6.3% MPO (Raghavendra et al., 2015).

Onychomycosis of the toenail Onychosis caused by Aspergillus versicolor

Fig 1 caption. Distal-lateral subungual onychomycosis due to Aspergillus ochraceopetaliformis (left); mixed-pattern onychomycosis (total dystrophic onychomycosis and superficial white onychomycosis) due to Aspergillus candidus (middle); yellowish pigmentation of the nail plate with mild hyperkeratosis due to Aspergillus versicolor (right).


A positive direct microscopy, repeated culture or molecular detection of Aspergillus spp., provided no dermatophyte was isolated, is sufficient to diagnose Aspergillus onychomycosis.

The isolation of Aspergillus spp. from nail specimens may mean several things: causative agent, colonizer or contaminant. The diagnosis of onychomycosis due to Aspergillus spp. is both clinical and mycological. Since there are no specific signs associated with onychomycosis due to Aspergillus spp., it is not possible to diagnose it based solely on physical appearance.

Microscopy of nail clippings yields positive results in 84% of cases (Gianni and Romano, 2004). Mycological culture on Sabouraud’s dextrose agar with or without cycloheximide yields fungal isolates in less than 50% of the cases. However, combining KOH preparation and culture, sensitivity is increased to 85.8% (Grover, 2003). Isolation rate is higher for nail samples obtained by drilling (83%) compared to scraping (67%) (Kashyap et al., 2008).

The differential diagnosis for onychomycosis due to Aspergillus spp. is very broad and includes yeast nail infections, tinea unguium, non-Aspergillus spp. NDMO, and other non-fungal nail infections and disorders.

Aspergillus versicolor cultureAspergillus versicolor cultureH&E stain of nail tissue with onychomycosis

Aspergillus versicolor grown on malt extract agar (left) and Sabouraud agar (middle). H&E staining of a sample of nail infected with Aspergillus ochraceopetaliformis.



Aspergillus spp. isolated from nail specimens are not usually susceptible to most of the topical and systemic antifungals used to treat dermatophytes. Inadequate treatment may lead to resistance and recurrence of infection. It should be noted that comparative clinical trials on the treatment of Aspergillus onychomycosis have not been done to date, and that recommendations have been based on case studies.

Several reports have described the efficacy of itraconazole (200mg daily) for Aspergillus onychomycosis (Scher and Barnett, 1990) and pulsed terbinafine (Gianni and Romano, 2004). The duration of therapy depends on which nails are affected and the extent of infection. Affected fingernails typically require 3 months of therapy and toenails at least 6 months. Itraconazole performs better than terbinafine in vitro (Ameen et al., 2014).

Topical amorolfine hydrochloride 0.25% is not always active against Aspergillus spp. (Li et al., 2004) and is not recommended, although one patient is described with A. candidus onychomycosis whose affected big toenail did respond to 6 months of therapy (Piraccini et al., 2002). If only one nail is affected alternative options include avulsion (removal) of the nail or dissolution of the nail with urea paste (BSMM, 1995).      



Citing this page

Bongomin F, Denning DW. Onychomycosis due to Aspergillus species [Internet]. Aspergillus & Aspergillosis website. 2017 [cited 2017 Nov 1]. Available from: www.aspergillus.org.uk/content/onychomycosis-1





Adhikari L, Gupta AD, Pal R, Singh TSK. Clinico-etiologic correlates of onychomycosis in Sikkim. Indian J Pathol Microbiol. 2009;52(2):194–197.

Afshar P Khodavaisy S KSGMRT. Onychomycosis in North-East of Iran. Iran J Microbiol. 2014;6(2):98–103.

Aghamirian MR, Ghiasian SA. Onychomycosis in Iran: Epidemiology, causative agents and clinical features. Jpn J Med Mycol. 2010;51(1):23–29.

Ameen M, Lear J t., Madan V, Mohd Mustapa M f., Richardson M. British Association of Dermatologists’ guidelines for the management of onychomycosis 2014. Br J Dermatol. 2014 Nov 1;171(5):937–58.

Banu A, Anand M, Eswari L. A rare case of onychomycosis in all 10 fingers of an immunocompetent patient. Indian Dermatol Online J.2013;4(4):302–304.

Bassiri-Jahromi S, Khaksar A. Nondermatophytic moulds as a causative agent of onychomycosis in Tehran. Indian J Dermatol. 2010;55(2):140.

Bokhari MA, Hussain I, Jahangir M, Haroon TS, Aman S, Khurshid K. Onychomycosis in Lahore, Pakistan. Int J Dermatol. 1999;38(8):591–595.

Bonifaz A, Cruz-Aguilar P, Ponce RM. Onychomycosis by molds. Report of 78 cases. Eur J Dermatol EJD. 2007 Feb;17(1):70–2.

Boukachabine K, Agoumi A. Onychomycosis in Morocco: experience of the parasitology and medical mycology laboratory from Rabat children hospital (1982-2003) Ann Biol Clin. 2005;63(6).

Chadeganipour M, Mohammadi R. Causative Agents of Onychomycosis: A 7-Year Study. J Clin Lab Anal. 2016;30(6):1013–1020.

Das MK, Ehrlich KC, Cotty PJ. Use of pyrosequencing to quantify incidence of a specific Aspergillus flavus strain within complex fungal communities associated with commercial cotton crops. Phytopathology. 2008 Mar;98(3):282–8.

Denning DW, Evans EG, Kibbler CC, Richardson MD, Roberts MM, Rogers TR, et al.Fungal nail disease: a guide to good practice (report of a Working Group of the British Society for Medical Mycology). BMJ. 1995 Nov 11;311(7015):1277–81.

Dhib I, Fathallah A, Yaacoub A, Zemni R, Gaha R, Said MB.Clinical and mycological features of onychomycosis in central Tunisia: A 22-year retrospective study (1986-2007). Mycoses. 2013;56(3):273–280.

English MP, Atkinson R. Onychomycosis in elderly chiropody patients. Br J Dermatol. 1974;91(1):67–72.

Gianni C, Romano C. Clinical and histological aspects of toenail onychomycosis caused by Aspergillus spp.: 34 cases treated with weekly intermittent terbinafine. Dermatology. 2004;209(2):104–110.

Godoy-Martinez P, Nunes FG, Tomimori-Yamashita J, Urrutia M, Zaror L, Silva V, et al. Onychomycosis in São Paulo, Brazil. Mycopathologia. 2009;168(3):111–116.

Grover S. Clinico-mycological evaluation of onychomycosis at Bangalore and Jorhat. Indian J Dermatol Venereol Leprol. 2003;69(4):284–286.

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. 2012;66(3):494–502.

Gupta M, Sharma NL, Kanga AK, Mahajan VK, Tegta GR. Onychomycosis: Clinico-mycologic study of 130 patients from Himachal Pradesh, India. Indian J Dermatol Venereol Leprol. 2007 Nov 1;73(6):389.

Gupta AK, Ryder JE, Baran R, Summerbell RC. Non-dermatophyte onychomycosis. Dermatol Clin. 2003 Apr 1;21(2):257–68.

Hajoui FZ, B Ghfir, Moustachi A, Lyagoubi M, Aoufi S. The mould onychomycosis in Morocco: About 150 isolated cases in 20 years. J Mycol Medicale. 2012;22(3):221–224.

Hashemi SJ, Gerami M, Zibafar E, Daei M, Moazeni M, Nasrollahi A. Onychomycosis in Tehran: Mycological study of 504 patients: Original article. Mycoses. 2010;53(3):251–255.

Hilmioğlu-Polat S, Metin DY, İnci R, Dereli T, Kılınç I, Tümbay E. Non-dermatophytic Molds as Agents of Onychomycosis in Izmir, Turkey – A Prospective Study. Mycopathologia. 2005 Sep 1;160(2):125–8.

Kaur R, Kashyap B, Makkar R. Evaluation of clinicomycological aspects of onychomycosis. Indian J Dermatol. 2008;53(4):174.

Kwon-Chung KJ, Sugui JA. Aspergillus fumigatus--what makes the species a ubiquitous human fungal pathogen? PLoS Pathog. 2013;9(12):e1003743.

Lange M, Roszkiewicz J, Szczerkowska-Dobosz A, Jasiel-Walikowska E, Bykowska B. Onychomycosis is no longer a rare finding in children. Mycoses. 2006;49(1):55–59.

Leelavathi M, Tzar MN, Adawiah J. Common microorganisms causing onychomycosis in tropical climate. Sains Malays. 2012;41(6):697–700.

Li R, Wan Z, Wang A, Shen Y, Lu C, Li M, et al. In vitro susceptibility testing of amorolfine in pathogenic fungi isolated from dermatomycosis patients in China. Mycoses 2004;(8):402–406.       

McAleer R. Fungal infections of the nails in Western Australia. Mycopathologia. 1981 Feb 13;73(2):115–20.

Lim JT, Chua HC, Goh CL. Dermatophyte and NonDermatophyte Onychomycosis in Singapore. Australas J Dermatol. 1992;33(3):159–163.

Manzano-Gayosso P, Hernández-Hernández F, Méndez-Tovar LJ, Palacios-Morales Y, Córdova-Martínez E, Bazán-Mora E, et al. Onychomycosis incidence in type 2 diabetes mellitus patients. Mycopathologia. 2008;166(1):41–45.

Martínez-Culebras P, Selma MV, Aznar R. Multiplex Detection of Aspergillus Species. Methods Mol Biol Clifton NJ. 2017;1542:261–8.

Mikaeili A, Karimi I. The incidence of onychomycosis infection among patients referred to hospitals in Kermanshah province, Western Iran. Iran J Public Health. 2013;42(3):320–325.

Moore M, Weiss RS. Onychomycosis Caused by Aspergillus Terreus. J Invest Dermatol. 1948;11(3):215–223.

Morales-Cardona CA, Valbuena-Mesa MC, Alvarado Z, Solorzano-Amador A. Non-dermatophyte mould onychomycosis: a clinical and epidemiological study at a dermatology referral centre in Bogota, Colombia. Mycoses. 2014 May 1;57(5):284–93.

Motamedi M, Ghasemi Z, Shidfar MR, Hosseinpour L, Khodadadi H, Zomorodian K, et al. Growing incidence of non-dermatophyte onychomycosis in tehran, Iran. Jundishapur J Microbiol. 2016;9(8).

Moubasher AH, Abdel-Sater MA, Soliman Z. Incidence and biodiversity of yeasts, dermatophytes and non-dermatophytes in superficial skin infections in Assiut, Egypt. J Mycol Medicale. 2017;27(2):166–179.

Nascimento M do DSB, Leitao VMS, da Neto Silva MAC, Maciel LB, Filho Muniz WE, Viana GM de C, et al. Eco-epidemiologic study of emerging fungi related to the work of babacu coconut breakers in the State of Maranhao, Brazil. Rev Soc Bras Med Trop. 2014;47(1):74–78.

Nkondjo Minkoumou S, Fabrizi V, Papini M. Onychomycosis in Cameroon: A clinical and epidemiological study among dermatological patients. Int J Dermatol. 2012;51(12):1474–1477.

Nouripour-Sisakht S, Mirhendi H, Shidfar MR, Ahmadi B, Rezaei-Matehkolaei A, Geramishoar M, et al. Aspergillus species as emerging causative agents of onychomycosis. J Mycol Medicale. 2015;25(2):101–107.

Ogawa M, Sugita S, Watanabe K, Shimizu N, Mochizuki M. Novel diagnosis of fungal endophthalmitis by broad-range real-time PCR detection of fungal 28S ribosomal DNA. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2012 Dec;250(12):1877–83.

Onsberg P, Stahl D, Veien NK. Onychomycosis caused by Aspergillus terreus. Sabouraudia. 1978 Mar;16(1):39–46.

Piérard G. Onychomycosis and Other Superficial Fungal Infections of the Foot in the Elderly: A Pan-European Survey. Dermatology. 2001;202(3).

Piraccini B, Lorenzi S, Tosti A. ‘Deep’ white superficial onychomycosis due to molds. J Eur Acad Dermatol Venereol. 2002 Sep 1;16(5):532–3.

Piraccini BM, Tosti A. White Superficial Onychomycosis: Epidemiological, Clinical, and Pathological Study of 79 Patients. Arch Dermatol. 2004 Jun 1;140(6):696–701.

Raghavendra K, Yadav D, Kumar A, Sharma M, Bhuria J, Chand A. The nondermatophytemolds: Emerging as leading cause of onychomycosis in south-east Rajasthan. Indian Dermatol Online J. 2015;6(2):92.

Ramani R, Srinivas C, Ramani A, Kumari TGR, Shivananda PG.MOLDS IN ONYCHOMYCOSIS. Int J Dermatol. 32(12):877–879.

Ranawaka RR, de Silva N, Ragunathan RW. Non-dermatophyte mold onychomycosis in Sri Lanka. Dermatol Online J. 2012;18(1):7.

Richardson MD. Effect of Lamisil and azole antifungals in experimental nail infection. Dermatol Basel Switz. 1997;194 Suppl 1:27–31.

Romano C, Papini M, Ghilardi A, Gianni C. Onychomycosis in children: A survey of 46 cases. Mycoses. 2005;48(6):430–437.

Romano C, Gianni C, Difonzo EM. Retrospective study of onychomycosis in Italy: 1985–2000. Mycoses. 2005 Jan 1;48(1):42–4.

Scher RK, Barnett JM. Successful treatment of Aspergillus flavusonychomycosis with oral itraconazole. J Am Acad Dermatol. 1990 Oct1;23(4):749–50.

Shahzad M, Alzolibani AA, Al Robaee AA, Bin Saif GA, Babikir IHK, Abdel-Magied EM, et al.Onychomycosis in Qassim region of Saudi Arabia: A clinicoaetiologic correlation. J Clin Diagn Res. 2014;8(8):1–4.

Soltani M, Khosravi AR, Shokri H, Sharifzadeh A, Balal A. A study of onychomycosis in patients attending a dermatology center in Tehran, Iran. J Mycol Medicale. 2015;25(2):e81–e87.

Souza LKH, Fernandes OFL, Passos XS, Costa CR, Lemos JA, Silva MRR. Epidemiological and mycological data of onychomycosis in Goiania, Brazil. Mycoses. 2010;53(1):68–71.

Surjushe A, Kamath R, Oberai C, Saple D, Thakre M, Dharmshale S, et al. A clinical and mycological study of onychomycosis in HIV infection. Indian J Dermatol Venereol Leprol. 2007 Nov 1;73(6):397.

Torres-Rodríguez JM, Madrenys-Brunet N, Siddat M, López-Jodra O, Jimenez T. Aspergillus versicolor as cause of onychomycosis: report of 12 cases and susceptibility testing to antifungal drugs. J Eur Acad Dermatol Venereol. 1998 Jul 1;11(1):25–31.

Tosti A, Piraccini BM, Lorenzi S, Iorizzo M. Treatment of nondermatophyte mold and Candida onychomycosis. Dermatol Clin. 2003 Jul;21(3):491–497, vii.

Tosti A, Piraccini BM. Proximal subungual onychomycosis due to Aspergillus niger: report of two cases. Br J Dermatol. 1998 Jul;139(1):156–7.

Vasconcellos C, Pereira CQM, Souza MC, Pelegrini A, Freitas RS, Takahashi JP. Identification of fungi species in the onychomycosis of institutionalized elderly. Anais Brasileiros de Dermatologia. 2013;88(3):377–380.

Veer P, Patwardhan NS, Damle AS. Study of onychomycosis: Prevailing fungi and pattern of infection. Indian J Med Microbiol. 2007 Jan 1;25(1):53.

Wijesuriya T, Kottahachchi J, Gunasekara TDCP, Bulugahapitiya U, Ranasinghe KNP, Neluka Fernando S, et al. Aspergillus species: An emerging pathogen in onychomycosis among diabetics. Indian J Endocrinol Metab. 2015;19(6):811.

Zaias N, Escovar SX, Rebell G.Opportunistictoenail onychomycosis. the fungal colonization of an available nailunit space by non-dermatophytes is produced by the trauma of the closedshoe by an asymmetric gait or other trauma. A plausible theory. J Eur Acad Dermatol Venereol. 2014;28(8):1002–1006.

Zotti M, Agnoletti AF, Vizzini A, Cozzani E, Parodi A. Onychomycosis from Aspergillus melleus, a Novel Pathogen for Humans. Fungal Identification and in vitro Drug Susceptibility. Exp Dermatol. 2015;24(12):966–968.




Dr. Felix Bongomin, MB ChB, M.Sc.

Clinical Research Associate

National Aspergillosis Centre

Education and Research Centre
Wythenshawe Hospital

Manchester University NHS Foundation Trust
Southmoor Road
Manchester M23 9LT UK

David W. Denning FRCP FRCPath FIDSA FMedSci
Professor of Infectious Diseases in Global Health
Director, National Aspergillosis Centre
Education and Research Centre
Wythenshawe Hospital

Manchester University NHS Foundation Trust
Southmoor Road
Manchester M23 9LT UK

November, 2017