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What The Research Reveals About The Use Of Urea For The Treatment Of Onychomycosis

Urea has long been an effective and safe treatment modality for numerous dermatologic disorders. The use of urea for the management of damaged, devitalized, dystrophic and mycotic nails is well documented.1 The mechanism of action of urea in the nail unit is unknown but studies suggest that urea exerts keratolytic and moisturizing effects by breaking hydrogen bonds. This subsequently loosens keratin and increases water-binding sites.2

Given urea’s keratolytic effects, physicians have used it in the treatment of onychomycosis. Numerous studies have shown combination therapy of urea and an antifungal agent to be an effective treatment for onychomycosis.3-12 Urea functions to soften the nail plate, which can enhance the passage of antifungal medications to the underlying nail bed. Analysis of the nail plate during treatment with bifonazole (Canespor, Bayer) and urea showed that during initial treatment, the corneocyte layers of the nail disintegrated, loosening the nail plate structure.3 After five days of treatment, the bifonazole led to morphologic changes of the fungal cells on the inferior surface of the nail plate.

Arievich and colleagues found that pretreatment of the nail plate with urea, hydrogen peroxide and thioglycolic acid allowed 10 times more topical terbinafine to pass through the nail plate in comparison to the application of terbinafine alone.4 Several studies have shown that combination therapy of urea plus topical antifungal agents has superior clinical outcomes in comparison to topical antifungal treatment alone. Specifically, research has shown combination therapies of topical urea with topical fluconazole, bifonazole, ciclopirox, propylene glycol, lactic acid, butenafine (Lotrimin, Bayer) and amphotericin B to have superior outcomes compared to topical antifungal monotherapy.5-12

Nail avulsion, either alone or to facilitate the treatment of the nail bed with topical antifungal agents, is another treatment option for onychomycosis. Several studies have shown that the application of 40% urea to the dystrophic nail plate under occlusion can produce successful chemical avulsion of dystrophic nails.13-15 Additionally, one can perform chemical nail avulsion with urea in patients with onychomycosis, thus removing pathologic nail tissue and facilitating the treatment of the nail bed with topical antifungal agents.6,14,16-18 Chemical avulsion has the benefits of not requiring anesthesia, avoiding bleeding, decreasing infection risk and improving patient function.19

Researchers have shown urea to be a very safe treatment modality with very few reported side effects. In the treatment of onychomycosis, adverse reactions including nail plate erosions, redness and tingling have reportedly only occurred in a very limited number of patients.5,6 With the use of urea for nail plate avulsion, only infrequent and transient side effects of skin irritation, maceration and adhesive dermatitis have occurred.13,20

The safety and efficacy of urea in numerous dermatologic disorders is well documented. With keratolytic and moisturizing mechanisms of action, urea is very useful in the treatment of both skin and nail disorders. Specifically, urea has been a successful treatment modality for onychomycosis as well as an effective agent for chemical nail avulsion.

References

1.      Pan M, Heinecke G, Bernardo S, Tsui C, Levitt J. Urea: a comprehensive review of the clinical literature. Dermatol Online J. 2013;19(11):20392.

2.      Gloor M, Fluhr J, Lehmann L, Gehring W, Thieroff-Ekerdt R. Do urea/ammonium lactate combinations achieve better skin protection and hydration than either component alone? Skin Pharmacol Appl Skin Physiol. 2002;15(1):35-43.

3.      Fritsch H, Stettendorf S, Hegemann L. Ultrastructural changes in onychomycosis during the treatment with bifonazole/urea ointment. Dermatology. 1992;185(1):32-36.

4.      Arievich AM, Vikhreva OG, Lebedev BM, Stepanischeva ZG. [Certain new principles and methods in the treatment of patients with onychomycoses]. Vestn Dermatol Venerol. 1960;34:30-35.

5.      Tsuboi R, Unno K, Komatsuzaki H, et al. [Topical treatment of onychomycosis by occlusive dressing using bifonazole cream containing 40% urea]. Nihon Ishinkin Gakkai Zasshi. 1998;39(1):11-16.

6.      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. J Dermatolog Treat. 2012;23(6):453-456.

7.      Aaron DL, Fadale PD, Harrington CJ, Born CT. Posttraumatic stress disorders in civilian orthopaedics. J Am Acad Orthop Surg. 2011;19(5):245-250.

8.      Emtestam L, Kaaman T, Rensfeldt K. Treatment of distal subungual onychomycosis with a topical preparation of urea, propylene glycol and lactic acid: results of a 24-week, double-blind, placebo-controlled study. Mycoses. 2012;55(6):532-540.

9.      Lurati M, Baudraz-Rosselet F, Vernez M, et al. Efficacious treatment of non-dermatophyte mould onychomycosis with topical amphotericin B. Dermatology. 2011;223(4):289-292.

10.    Baran R, Coquard F. Combination of fluconazole and urea in a nail lacquer for treating onychomycosis. J Dermatolog Treat. 2005;16(1):52-55.

11.    Shemer A, Bergman R, Cohen A, Friedman-Birnbaum R. [Treatment of onychomycosis using 40% urea with 1% bifonazole]. Harefuah. 1992;122(3):159-160.

12.    Syed TA, Ahmadpour OA, Ahmad SA, Shamsi S. Management of toenail onychomycosis with 2% butenafine and 20% urea cream: a placebo-controlled, double-blind study. J Dermatol. 1998;25(10):648-652.

13.    Farber EM, South DA. Urea ointment in the nonsurgical avulsion of nail dystrophies. Cutis. 1978;22(6):689-692.

14.    Lahfa M, Bulai-Livideanu C, Baran R, et al. Efficacy, safety and tolerability of an optimized avulsion technique with onyster(R) (40% urea ointment with plastic dressing) ointment compared to bifonazole-urea ointment for removal of the clinically infected nail in toenail onychomycosis: a randomized evaluator-blinded controlled study. Dermatology. 2013;226(1):5-12.

15.    Pandhi D, Verma P. Nail avulsion: indications and methods (surgical nail avulsion). Indian J Dermatol Venereol Leprol. 2012;78(3):299-308.

16.    Piraccini BM, Bruni F, Alessandrini A, Starace M. Evaluation of efficacy and tolerability of four weeks bifonazole treatment after nail ablation with 40% urea in mild to moderate distal subungual onychomycosis. G Ital Dermatol Venereol. 2016;151(1):32-36.

17.    Tietz HJ, 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):414-421.

18.    Baran R, Tosti A. Chemical avulsion with urea nail lacquer. J Dermatolog Treat. 2002;13(4):161-164.

19.    South DA, Farber EM. Urea ointment in the nonsurgical avulsion of nail dystrophies--a reappraisal. Cutis. 1980;25(6):609-612.

20.    Bonifaz A, Ibarra G. Onychomycosis in children: treatment with bifonazole-urea. Pediatr Dermatol. 2000;17(4):310-314.

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