The information – fungal nail infection

The patient’s unmet needs (PUNs)

A 40-year-old man attends the surgery and removes his sock. ‘I’ve been to the pharmacist about this fungus in my toenail.’ Examination reveals a thickened, crumbling, discoloured big toenail. He has no history of skin problems and his other nails are fine. ‘I assume the pharmacist’s right that it’s a fungus?’ he asks. ‘So should I take some pills?’

The doctor’s educational needs (DENs)

What are the characteristic clinical features of fungal nail infections, what are the possible differentials?

Fungal nail infections, or onychomycosis, have three patterns.

• The most common type is where the fungus infiltrates the nail and nail bed through the distal or lateral margins of the nail (distolateral subungual onychomycosis, DLSO) (Fig A).
• The second is where fungus invades the nail directly from above which leads to a white patchy discolouration of the nail surface (superficial white onychomycosis, SWO) (Fig B).
• The final and least common presentation is infection in the root of the nail, presenting at the proximal margin beneath the nail plate as it emerges from the proximal nail fold (proximal subungual onychomycosis, PSO). This is associated with immune suppression and needs expert evaluation (Fig C).

All possible fungal infections should be confirmed by generous clippings of nail and subungual debris for microscopy and culture prior to starting systemic treatment.

The most commonly missed diagnoses that are managed as fungal nail infections are chronic trauma and psoriasis.

Benign and malignant tumours around the nail are also commonly misdiagnosed as fungal infection. Malignant tumours are normally distinguished by black pigment for melanoma or ooze and crusting if SCC or amelanotic metlanoma.

Other conditions that can be mistaken for fungal nail disease are lichen planus, bacterial paronychia, onycogryphosis, rare systemic diseases such as yellow-nail syndrome and drug reactions.

Fig A. Distolateral subungual onychomycosis (DLSO). Note the fungus infiltrates the nail and nail bed through the distal or lateral margins of the nail.

Fig B. Superficial white onychomycosis (SWO). The fungus invades the nail directly from above which leads to a white patchy discolouration of the nail surface. There is usually a powdery consistency to the nail surface also.

Fig C. Proximal subungual onychomycosis (PSO). Note the infection in the root of the nail presenting at the proximal margin beneath the nail plate as it emerges from the proximal nail fold. This presentation is associated with immune suppression.

Is it necessary to have a positive result from nail clippings to make a definite diagnosis? How common are false-negative results with clippings?

The risks of misdiagnosing fungal nail infections are significant. Systemic antifungals can be hepatotoxic and there is the risk of not treating another underlying problem such as a malignancy if nail changes are misinterpreted as fungus, with consequent delay in making the correct diagnosis.

Diagnosis is made through clinical appearance matched with positive microscopy and culture of nail clippings.

A recent survey from Europe showed this was undertaken by only 3.4% of primary care physicians and roughly 40% of dermatologists.¹ False-negative results are common (30-50%), although repeated sampling will reduce the chance of a false-negative diagnosis.

What is the prognosis for an untreated fungal nail infection? Is it always necessary to treat?

There is no data on progression of untreated fungal nail disease. Tinea pedis and fungal nail disease are associated and tinea pedis is a predisposing factor for cellulitis. Where they are seen together, there is an argument for treatment of fungal nail disease to prevent relapse of tinea pedis with attendant risks.

Fungal nail disease has been documented in patterns within families that would be consistent with transmission within the home or shared genetic disposition.

How effective are topical treatments?

There are two main topical treatments, amorolfine 5% and tioconazole 28% suitable in DLSO of the distal third and superficial infection (SWO). Combining these therapies with debridement may increase success. These is limited evidence to suggest amorolfine 5% cures distal dermatophyte fungal nail disease in 38-54% when used twice weekly for six months.^2,3 Open trial of tioconazole for six months suggests a cure rate of between 20-70%.

How effective is oral treatment? What would the approach be if there was no apparent clinical benefit after some months?

Oral treatment has higher efficacy but also greater risk. A trial comparing itraconazole to terbinafine demonstrated ‘clinical cure’ in 54% after 12 weeks terbinafine and 32% after three pulses of itraconzole at monthly intervals.⁴ There is some evidence that combining amorolfine and systemic treatments increases cure rate.⁵

 If there is no clinical benefit from systemic treatment after three months then the diagnosis should be reconsidered.

The explanation could be that trauma or psoriasis are the cause of the changes or that the fungus is a non-dermatophyte (mould) such as Fusarium sp., although as stated above, the fungal infection is usually established by culture from clippings prior to starting treatment.

Genuine fungal nail disease not responding to systemic therapy can sometimes respond to partial or complete nail avulsion, followed by ketoconazole cream used under cling film occlusion until full nail regrowth. Other non-responding disease should be assessed for an alternative diagnosis including melanoma and squamous cell carcinoma.

David de Berker is a consultant dermatologist and honorary clinical senior lecturer at Bristol Dermatology Centre, Bristol Royal Infirmary, Bristol

Dr William Hunt is an FY1 doctor at The Royal Devon and Exeter Hospital

References

1 Effendy I, Lecha M, Feuilhade de Chauvin M et al. (2005) Epidemiology and clinical classification of onychomycosis. Journal of the European Academy of Dermatology and Venereology,19 (Suppl.1); 8-12

2 Lauharanta J. (1992) Comparative efficacy and safety of amorolfine nail lacquer 2% versus 5% once weekly. Clinical and Experimental Dermatology,17 (Suppl. 1); 41-43

3 Reinel D. (1992) Topical treatment of onychomycosis with amorolfine 5% nail lacquer: comparative efficacy and tolerability of once and twice weekly use. Dermatology, 184 (Suppl. 1); 21-24

4 Evans EG, Sigurgeirsson B. (1999) Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis. BMJ, 318 (7190); 1031-1035

5 Baran R, Sigurgeirsson B, de Berker D, et al. (2007) A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement. British Journal of Dermatology, 157 (1); 149-157

Further reading

Roberts DT, Taylor WD, Boyle J. (2003) Guidelines for treatment of onychomycosis. British Journal of Dermatology, 148 (3); 402-410