Effectiveness of modified Whitfield’s ointment with oral griseofulvin in the treatment of dermatophytosis poorly responsive to standard antifungal therapy: a randomized, double blind, within patient placebo control
Background: Dermatophytosis is a superficial fungal infection found in hot and humid areas particularly in tropical regions and affects the keratinized regions of the body. It is usually treated with a combination of topical and systemic antifungal therapy as well as improved hygienic measures. Over the last few decades there has been an increase in the prevalence of dermatophyte infections which are poorly responding to standard antifungal therapy.
Methods: Modified Whitfield’s ointment is a combination of 5%-5% Salicylic acid and Benzoic acid with an emulsifying ointment as a vehicle which has both a fungistatic and a keratolytic action. Oral Griseofulvin is a systemic antifungal agent which is a fungistatic agent. The combination of the above agents is synergistic. A randomized double blind, within-patient-placebo-controlled trial was designed for the treatment of dermatophytosis poorly responsive to standard antifungal therapy.
Conclusions: This may shed light on the treatment of dermatophytosis poorly responsive to standard antifungal therapy.
Trial Registration: This trial is registered with WHO trial registry number (Universal trial number): U111-1235-8791.
White JFPHTJGKDLN. Manson’s Tropical Diseases. 23rd edition. Saunder's Ltd; 2013: 1360.
Gooskens V, Pönnighaus JM, Clayton Y, Mkandawire P, Sterne JAC. Treatment of superficial mycoses in the tropics: Whitfield's ointment versus clotrimazole. Int Dermatol. 1994;33(10):738-42.
Gupta AK, Ryder JE, Chow M, Cooper EA. Dermatophytosis: the management of fungal infections. Skinmed. 2005;4(5):305-10.
Lesher JL. Oral therapy of common superficial fungal infections of the skin. Am Acad Dermatol. 1999;40(6):S31-4.
Tamura T, Asahara M, Yamamoto M, Yamaura M, Matsumura M, Goto K, et al. In vitro susceptibility of dermatomycoses agents to six antifungal drugs and evaluation by fractional inhibitory concentration index of combined effects of amorolfine and itraconazole in dermatophytes. Microbiol Immunol. 2014;58(1):1-8.
Rengasamy M, Chellam J, Ganapati S. Systemic therapy of dermatophytosis: Practical and systematic approach. Clin Dermatol Rev. 2017;1(3):19-23.
Sharma M, Palanichamy T. Psychosocial interventions for technological addictions. Indian J Pathol Microbiol. 2017;60(4):541-5.
Dogra S, Uprety S. The menace of chronic and recurrent dermatophytosis in India: Is the problem deeper than we perceive? Indian Dermatol Online J. 2016;7(2):73-6.
Singh S, Verma P, Chandra U, Tiwary N. Risk factors for chronic and chronic-relapsing tinea corporis, tinea cruris and tinea faciei: Results of a case–control study. Indian J Dermatol Venereol Leprol. 2019;85(2):197-200.
Panda S, Verma S. The menace of dermatophytosis in India: The evidence that we need. Indian J Dermatol Venereol Leprol. 2017;83(3):281-4.
Verma SB. Emergence of recalcitrant dermatophytosis in India. Lancet Infect Dis. 2018;18(7):718-9.
Sonthalia S, Agrawal M, Goldust M, Das S, Bhattacharya SN. Antifungal therapeutic failures in India: an important issue being overlooked. Lancet Infect Dis. 2018;18(11):1181-2.
Bishnoi A, Vinay K, Dogra S. Emergence of recalcitrant dermatophytosis in India. Lancet Infect Dis. 2018;18(3):250-1.
Mukherjee PK, Leidich SD, Isham N, Leitner I, Ryder NS, Ghannoum MA. Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemotherapy. 2003;47(1):82-6.
Osborne CS, Leitner I, Favre B, Ryder NS. Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob Agents Chemotherapy. 2005;49(7):2840-4.
Goodman and Gilman’s The Pharmacological Basis of Therapies. 12 edition. McGraw-Hill; 2011.
NIH. Livertox: NIH: U.S. National Library of Medicine; 2019. Drug Record: Griseofulvin]. Available from: https://livertox.nih.gov/Griseofulvin.htm. Accessed 17 July 2019.
Peter Bakker HW, Vincent Gooskens, Ben Naafs, Rachel van der Kaaij, Nicolien Wieringa. Dermatological Preparations for the Tropics. 2nd edition. Beta Science Shop, University of Gronigren, Netherlands; 2012.
Bell-Syer SEM, Khan SM, Torgerson DJ. Oral treatments for fungal infections of the skin of the foot. Cochrane Database of Systematic Reviews. 2012;(10).
Crawford F, Hollis S. Topical treatments for fungal infections of the skin and nails of the foot. The Cochrane database of systematic reviews. 2007;(3):Cd001434.
Roberts DT, Cox NH, Gentles JC, Babu KK. Comparison of ketoconazole and griseofulvin in the treatment of tinea pedis. J Med Veterinary Mycol. 1987;25(5):347-50.
Savin RC. Oral terbinafine versus griseofulvin in the treatment of moccasin-type tinea pedis. J Am Acad Dermatol. 1990;23(4 Pt 2):807-9.
Hay RJ, Clayton YM, Griffiths WA, Dowd PM. A comparative double blind study of ketoconazole and griseofulvin in dermatophytosis. British J Dermatol. 1985;112(6):691-6.
Dabas Y, Xess I, Singh G, Pandey M, Meena S. Molecular Identification and Antifungal Susceptibility Patterns of Clinical Dermatophytes Following CLSI and EUCAST Guidelines. J Fungi. 2017;3(2):17.
Lana AJD, Pippi B, Carvalho AR, Moraes RC, Kaiser S, Ortega GG, et al. In Vitro additive effect on griseofulvin and terbinafine combinations against multidrug-resistant dermatophytes. Brazilian J Pharmaceutical Sci. 2018;54.
Galuppi R, Gambarara A, Bonoli C, Ostanello F, Tampieri M. Antimycotic effectiveness against dermatophytes: Comparison of two in vitro tests. 2010;S57-61.
Finzi A, Fioroni A, Preti PM, Mounari M. A Double Blind Evaluation of Fenticonazole Cream 2% and Clotrimazole Cream 1% in Dermatomycoses/Doppelblindstudie mit Fenticonazol-Creme 2%ig und Clotrimazol-Creme 1%ig bei Dermatomykosen. Mycoses. 1986;29(1):41-4.
Zaun H, Luszpinski P. Multicenter double-blind contralateral comparison of naftifin and clotrimazole cream in patients with dermatophytosis and candidiasis. Zeitschrift fur Hautkrankheiten. 1984;59(18):1209-17.
Holti G. A double-blind controlled trial of Whitfield's ointment and variotin in ringworm infections with a two year 'follow-up'. Acta Dermato-Venereologica. 1970;50(3):229-31.
Weller R, Ormerod AD, Hobson RP, Benjamin NJ. A randomized trial of acidified nitrite cream in the treatment of tinea pedis. J Am Acad Dermatol. 1998;38(4):559-63.
Sivayathorn A, Piamphongsant T. Topical Antimycotic Agents for the Treatment of Superficial Dermatophytoses in Thailand: A Double-Blind Study. Mycoses. 1979;22(1):21-4.