Why Should we Care if Onychomycosis is Truly Onychomycosis?

R.J. Hay; R. Baran


The British Journal of Dermatology. 2015;172(2):316-317. 

Onychomycosis, or fungal nail infection due to dermatophyte fungi, is one of the most common infections, with prevalence rates of toenail infection varying from 3% to over 25%. These rates depend on the country and method of case ascertainment;[1] the prevalence increases with age, with those aged over 70 years having infection rates, in some studies, of > 50%.[1] Other covariates include climate, nature of work and presence of underlying disease such as diabetes or psoriasis. It is a difficult infection to treat, as even the most effective measures, such as oral terbinafine combined with topical amorolfine, rarely produce clinical and mycological cures of more than 60–70% at follow-up.[2] These figures depend critically on the methods used to assess end points, and complete cure rates may be lower, even after lengthy treatment.[3,4] Therefore preventing relapse or anticipating infection through early intervention has long been a desirable strategy. Many dermatologists advise patients who have had onychomycosis to treat any new signs of interdigital or plantar tinea pedis at the earliest opportunity, or to seek advice if there are any new abnormal nail signs. This is founded on the belief that a new nail infection can be prevented by treating the infection on the foot or the nail by simple measures such as topical antifungals, before oral therapy becomes necessary.

That all was not well with such advice was first apparent when two studies showed that, in patients with minimal primary onycholysis, and also in some with apparently normal nails, there was a small risk that dermatophytes could be identified by both microscopy and culture.[5,6] This was subsequently confirmed in patients with clinically normal nails but symptomatic tinea pedis.[7]

The study by Shemer et al.[8] in the current issue of BJD confirms and extends these earlier observations by showing that a small but significant number of patients with apparently normal nails, and without clinical infection on the skin of the foot, have dermatophytes in their nails. These studies suggest that preventing recurrence of the nail infection by treating tinea pedis or minimal nail abnormalities as soon as these appear might not be effective, as the clinical signs may not be accurate predictors of infection.

One key observation mentioned by the authors is that the organisms present in normal nail identified in this study might not have evolved into a fully established nail infection. This might be confirmed, or not, by a difficult long-term follow-up study of the presence of fungi in both skin and nails at different time points after successful treatment of onychomycosis. Alternatively, certain genes are switched on when dermatophytes invade keratinized tissue and, if demonstrated in patients with dermatophytes in normal nails, the fungus would be in 'invasive mode'. At least four such gene classes have been identified.[9] These are (i) proteases that can degrade epidermal proteins including keratin; (ii) kinases involved in signalling; (iii) secondary metabolites such as polyketide synthases, involved in interactions between fungus and host; and (iv) LysM (lysin motif) proteins that help the organism evade host surveillance.

But why is this important, as onychomycosis is not thought to be disabling? Although there are few direct studies there is indirect evidence that there is a strong medical need to deal with onychomycosis in at least two different populations: diabetics and the frail elderly. In diabetes, both tinea pedis and fungal nail infection are risk factors for diabetic foot.[10] Onychomycosis is also common in elderly patients, potentially a larger source of concern and one that will increase over the next few years. Among the risk factors for falls, which so often precipitate a crisis in the care of the frail elderly, are nail deformity[11] and foot-related pain, including pain in the nails.[12] At this stage there have been no studies that have investigated the comparative risk of falls in patients with and without onychomycosis, but two of the consequences of nail plate infection are pain and nail deformity. The question, therefore, as to when onychomycosis is really onychomycosis is not simply an academic whim but may have real relevance to the effective management of what is for some a not-so-trivial disease.