Total dystrophic onychomycosis (TDO) is seen as the end stage of fungal nail infection where the nail plate becomes almost totally infected. The condition occurs slowly and progresses most often from untreated distal-lateral sub-ungual (DLSO) nail disease.
At this point, management becomes more difficult and treatment frequently yields poor results. Topical medicines such as amorolfine 5% (Loceryl® & Curanail®) are unlikely to have a significant effect (as they are only indicated for mild to moderate disease) and as a clinician you maybe tempted to consider a prescription for a systemic antifungal agent as these are the only drugs which are indicated for severe fungal nail infection. Alternatively, a total nail avulsion under local anaesthesia maybe the only other option to expose the nail bad and allow effective removal of the infection.
However, as an alternative what about performing a “medical” nail avulsion? This is something I first came across as a student in the 1980’s whilst reading “Baran and Dawber’s Diseases of the Nail and Their Management” (published in 1984). The particular chapter referred to using 40% urea “under occlusion” to painlessly dissolve away fungal nail. The power of urea is something which I have previously written about particularly with reference to the skin (1) but not so much about its effects on the nail. Urea is a substance we normally think about as a waste product – a substance created by the liver and removed by the kidneys with little biological value. However, as we now know urea is a naturally produced within the skin as a humectant to retain moisture within the epidermis (2).
The hydrating effects of urea have been observed – as a humectant it is able to attract and hold water within the epidermis giving it excellent emollient properties. Urea, as a small molecule also has the ability to cause conformational change in skin protein structures, effectively unfolding them making them more vulnerable to degradation and exfoliation – clinically this is seen as an epidermal thinning effect (3) without affecting normal skin physiology and integrity. This function being evident in lower strength formulations (less than 20%).
Above 25%, its action becomes more like salicylic acid as a keratolytic than a hydrating agent (4). The higher percentage formulations are used in the treatment of hyperkeratotic disorders of the skin. Moreover at this concentration urea, under occlusion, is able to dissolve the harder keratin of nails and has been used as a means of debriding diseased nail in combination with an antifungal treatment (5, 6) or as a direct means of removing infected nail (7). Other studies have studied it use as an initial treatment to remove the nail in conjunction with an antifungal agent applied or taken after the nail has been avulsed using urea (8, 9). Adverse events and side effects of its use have reported only minor issues such as redness and tingling at the point of application (10, 11).
The outcomes of these and other studies have clearly demonstrated a place for urea in the treatment of severely infected nails and additionally, the patient reported outcomes for these cases have been generally favourable. Having used urea treatment on patients nails I would add a word of caution. Urea (at 40%) is easily able to dissolve fungally-infected nail but is less effective at removing healthy nail – this may seem like a clinical advantage but to clarify, from my own experience, as the urea is applied topically, it does not work as well for sub-ungual infection. This is because the overlying nail plate is generally healthy, so the urea works less effectively. Of course, reduction with a drill prior to treatment can help but this but be aware of its reduced effectiveness in these situations.
In the UK, 40% urea can now be purchased by patients from pharmacies. Canespro® (Bayer) is a kit containing a tube of 40% urea paste, plasters and nail files. In my own experience, providing this at the clinic means that at the patient’s appointment I am able to reduce any thickening of the nail as well as demonstrate the application of the urea and plasters. The patient then wears the plasters for around 24/48 hours before removing and reapplying the paste and re-covering it with the supplied plasters. Avulsion for most takes around two weeks. Despite the products branding resembling Canesten®, it contains no medical anti-fungal agent so following successful avulsion, it’s about treating the nail bed and skin with a topical agent such as terbinafine or clotrimazole as the new nail grows through to ensure it stays free of infection. As with all tinea pedis, it frequently relapses so patients should be advised to remain vigilant for signs of reinfection and treat this promptly when it arises.
Overall, the use of 40% urea in the treatment of fungal nails is an attractive option especially as compared to surgical removal, it can reduce the risk of bacterial infection, requires no anaesthetic and is relatively painless. However, as the treatment may require a few applications to work fully, patients will need to re-apply this themselves and so will need to be agile enough to reach their feet and redress them as required.
In a future article, I will include some case studies demonstrating its use in clinic. Canespro® is a trademark of Bayer. The kit retails in the UK at around £30.
Clinical Footnote
In the UK, 40% urea is also available in some hand cream preparations, however in my experience, despite their significantly lower price, they are less effective for nail softening as they are more liquid and therefore more difficult apply and less likely to remain in place on a nail to have a positive benefit. The Canespro product is a stiff paste which stays in situ much more easily.
References
1. Bristow IR. Urea - the gold standard for emollients? Podiatry Now. 2016;19(10):20-3.
2. Grether-Beck S, Felsner I, Brenden H, Kohne Z, Majora M, Marini A, et al. Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression. J Invest Dermatol. 2012;132(6):1561-72.
3. Fluhr JW, Cavallotti C, Berardesca E. Emollients, moisturizers, and keratolytic agents in psoriasis. Clin Dermatol. 2008;26(4):380-6.
4. Vidal I, Sanchez M, De la Cruz G, Trullas C, Galavany L, Marquez G, et al. Using Urea at high concentrations: clinical cases. In: EADV September Meeting, editor. Poster presentation,. Paris, France2008.
5. Baran R, Coquard F. Combination of fluconazole and urea in a nail lacquer for treating onychomycosis. The Journal of dermatological treatment. 2005;16(1):52-5.
6. Hardjoko FS, Widyanto S, Singgih I, Susilo J. Treatment of onychomycosis with a bifonazole-urea combination. Mycoses. 1990;33(4):167-71.
7. Baran R, Tosti A. Chemical avulsion with urea nail lacquer. The Journal of dermatological treatment. 2002;13(4):161-4.
8. Tietz H-J, Hay R, Querner S, Delcker A, Kurka P, Merk HF. Efficacy of 4 weeks topical bifonazole treatment for onychomycosis after nail ablation with 40% urea: a double-blind, randomized, placebo-controlled multicenter study. Mycoses. 2013;56(4):414-21.
9. Friedman‐Birnbaum R, Cohen A, Shemer A, Bitterman O, Bergman R, Stettendorf S. Treatment of onychomycosis: a randomized, double‐blind comparison study with topical bifonazole‐urea ointment alone and in combination with short‐duration oral griseofulvin. Int J Dermatol. 1997;36(1):67-9.
10. Tsuboi R, Unno K, Komatsuzaki H. [Topical treatment of onychomycosis by occlusive dressing using bifonazole cream containing 40% urea]. Nihon Ishinkin Gakkai Zasshi 1998;39(1):11-6.
11. Bassiri-Jahromi S, Ehsani AH, Mirshams-Shahshahani M, Jamshidi B. A comparative evaluation of combination therapy of fluconazole 1% and urea 40% compared with fluconazole 1% alone in a nail lacquer for treatment of onychomycosis: therapeutic trial. The Journal of dermatological treatment. 2012;23(6):453-6.