ORIGINAL RESEARCH Novel Treatment of Onychomycosis using Over-the-Counter Mentholated Ointment: A Clinical Case Series Richard Derby MD, Patrick Rohal MD, Constance Jackson MD, Anthony Beutler MD, and Cara Olsen PhD, MPH Background: Current medication treatments for onychomycosis have less than full cure-rate efficacy and have the potential for adverse side effects. Vicks VapoRub (The Proctor & Gamble Company, Cincinnati, OH) has been advocated in the lay literature as an effective treatment for onychomycosis. This pilot study tested Vicks VapoRub as a safe, cost-effective alternative for treating toenail onychomycosis. Methods: Eighteen participants were recruited to use Vicks VapoRub as treatment for onychomycosis. Participants were followed at intervals of 4, 8, 12, 24, 36, and 48 weeks; digital photographs were ob- tained during initial and follow-up visits. Primary outcome measures were mycological cure at 48 weeks and clinical cure through subjective assessment of appearance and quantifiable change in the area of affected nail by digital photography analysis. Patient satisfaction was a secondary outcome, measured using a single-item questionnaire scored by a 5-point Likert scale. Results: Fifteen of the 18 participants (83%) showed a positive treatment effect; 5 (27.8%) had a mycological and clinical cure at 48 weeks; 10 (55.6%) had partial clearance, and 3 (16.7%) showed no change. All 18 participants rated their satisfaction with the nail appearance at the end of the study as “satisfied” (n � 9) or “very satisfied” (n � 9). Conclusions: Vicks VapoRub seems to have a positive clinical effect in the treatment onychomycosis. ( J Am Board Fam Med 2011;24:69 –74.) Keywords: Mentholated Ointment, Onychomycosis, Treatment Toenail onychomycosis is a common diagnosis for primary care physicians. The prevalence of onych- omycosis in the North American adult population may range from 2% to 18%, with prevalence in- creasing to 20% and 30% for those older than 60 years and 70 years, respectively.1–5 Onychomycosis is commonly associated with tinea pedis. Signifi- cant physical and psychological effects, such as pain and negative self-image, may occur in patients with onychomycosis.6 Dermatophytes Trichophyton rubrum and Tricho- phyton mentagrophytes are the predominant patho- gens in onychomycosis; nondermatophytes (usually Candida) account for a smaller percentage (10% to 20%) of toenail onychomycosis.1,7 Presentation of infection may occur in various patterns: fungal in- vasion of distal or lateral margins of the nail (dis- tolateral subungual onychomycosis); direct effect from above or on top of the nail with a powdery, white, patchy discoloration (superficial white ony- This article was externally peer reviewed. Submitted 26 May 2010; revised 20 August 2010; accepted 30 August 2010. From the US Air Force 375th Medical Group, Family Medicine Residency Program, Belleville, IL (RD); the US Air Force 779th Medical Group, Department of Family Medicine, Malcolm Grow Medical Center, Joint Base An- drews, MD (PR); the US Air Force 28th Medical Group, Department of Family Medicine, Ellsworth AFB, SD (CJ); and the Departments of Family Medicine (AB) and Preven- tive Medicine and Biometrics (CO), Uniformed Services University, Bethesda, MD (AB). Funding: Funding as provided by the TRUE Research Foundation, San Antonio, TX. Conflict of interest: none declared. Disclaimer: The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Uni- formed Services University of the Health Sciences, the US Air Force, or the US Department of Defense. Corresponding author: Lt. Col. Richard Derby, 375th Medical Group, Family Medicine Residency Program, 180 S. Third Street, Suite 400, Belleville, IL 62220 (E-mail: Richard.derby-02@scott.af.mil). doi: 10.3122/jabfm.2011.01.100124 Treatment of Onychomycosis using Mentholated Ointment 69 o n 5 A p ril 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://w w w .ja b fm .o rg / J A m B o a rd F a m M e d : first p u b lish e d a s 1 0 .3 1 2 2 /ja b fm .2 0 1 1 .0 1 .1 0 0 1 2 4 o n 5 Ja n u a ry 2 0 1 1 . D o w n lo a d e d fro m http://www.jabfm.org/ chomycosis); or infection beginning from the prox- imal location beneath the nail bed (proximal sub- ungual onychomycosis).7 Current treatment agents for onychomycosis in- clude both systemic and topical medications. A meta-analysis of systemic therapies showed myco- logical cure rates of 76% with the use of terbinfine, 63% with the use of itraconazole pulse dosing, 61% with the use of griseofulvin, and 48% with the use of fluconazole.8 Downsides to oral therapy include the potential for adverse side effects, most notably hepatotoxicity, and the significant cost of the med- ication course, which is typically of 3 months’ du- ration. Ciclopirox 8% is a topical lacquer solution that has been approved by the US Food and Drug Administration for treatment of onychomycosis, with reported mycological cure rates of 34% in meta-analysis studies of North America patients.9 Cure rates of ciclopirox 8% and other topical ther- apies that have not been approved by the US Food and Drug Administration (eg, amorolfine 5% and tioconazole 28%) are lower than those observed with systemic treatments, and the course of topical treatments ranges from 6 to 12 months.7 Vicks VapoRub (The Proctor & Gamble Com- pany, Cincinnati, OH) has been popularized by lay medical Web sites as a home cure for onychomy- cosis.10 No published trials examining the effect of this compound on onychomycosis have been ac- complished. However, the active and inactive in- gredients in Vicks VapoRub (thymol, menthol, camphor, and oil of Eucalypus) have shown efficacy against dermatophytes in vitro.11–14 The purpose of this pilot study was to test the efficacy of Vicks VapoRub as a safe, cost-effective alternative for treating toenail onychomycosis in an outpatient clinic setting. Methods The study protocol was approved by the institu- tional review board of the Malcolm Grow US Air Force Medical Center. Participants were recruited from an outpatient family medicine clinic that serves both an active duty and civilian (dependent and retiree) populations. Information posters were placed in the clinic lobbies to advertise the study. Patients used contact details on the posters to ar- range an appointment with study investigators. During the initial appointment, the study was ex- plained and informed consent for participation was obtained. Demographic data (age, sex, military sta- tus) was obtained along with historic data (duration of dystrophic nail, prior treatment for onychomy- cosis, chronic medical diseases, medication use, and allergy history). Inclusion criteria were men and women older than 18 years of age with clinical onychomycosis that was evident on at least one great toenail. Ex- clusion criteria included any history of allergic sen- sitivity to Vicks VapoRub or its active ingredients (thymol, camphor, menthol, or oil of Eucalyptus); any use of oral antidermatophyte medication within the last year; any deformity of the affected nail that would preclude sampling for potassium hydroxide (KOH) and culture or prevent adequate photo- graphic assessment of the nail; and a negative cul- ture of fungal infection from the sampling taken during the initial visit. After consent was obtained, a digital photograph of the affected nail was taken, and then a nail wedge/clipping was collected for KOH microscopy and culture. The participant was then supplied with the study treatment (Vicks VapoRub) and in- structed to apply a small amount of Vicks VapoRub with a cotton swab or finger to the affected nail at least once daily. If the culture of the nail sample was negative for fungal infection, volunteers were con- tacted and removed from the study. Volunteers with positive cultures were contacted for follow-up assessments at 4, 8, 12, 24, 36, and 48 weeks. Re- peat digital photographs, assessment for adverse reactions, treatment effect, patterns of VapoRub use, and the patient’s perceived tolerability of treat- ment were performed/assessed during each visit. The primary outcome measures for the study were mycological cure at 48 weeks, defined as neg- ative KOH and culture of nail sample, and clinical cure (clearance of dystrophic nail). Clearance of dystrophic nail was assessed by gross appearance at the end of the study period as “complete,” “partial,” or “no change.” Clearance was quantified through serial digital photography of the affected nail. Pho- tographic editing software (Photoshop CS3, Adobe Systems, Inc., San Jose, CA) was used to define the nail edges and the borders of the affected nail region so areas (in pixel units) of total nail and affected nail could be calculated. Using these areas, the ratio of affected nail area to total nail area was calculated for each photograph taken during the course of the study. A secondary outcome mea- sured was patient satisfaction with the appearance 70 JABFM January–February 2011 Vol. 24 No. 1 http://www.jabfm.org o n 5 A p ril 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://w w w .ja b fm .o rg / J A m B o a rd F a m M e d : first p u b lish e d a s 1 0 .3 1 2 2 /ja b fm .2 0 1 1 .0 1 .1 0 0 1 2 4 o n 5 Ja n u a ry 2 0 1 1 . D o w n lo a d e d fro m http://www.jabfm.org/ of the affected nail at the end of the study period; this was assessed using a single-item questionnaire scored on a 5-point Likert scale (1 � very satisfied, 2 � satisfied, 3 � neither satisfied nor dissatisfied, 4 � dissatisfied, and 5 � very dissatisfied). Statistics Descriptive statistics were used to report outcome data. Paired t test and Fisher’s exact test were used to analyze significance of treatment effect from the initial to 48 week period and between infecting pathogen subtypes. Results Forty participants were recruited to the study over 10 months. Of these, 20 were removed because of a negative fungal culture result on the initial nail sampling. Two participants removed themselves from the study (1 at 12 weeks and the other at 24 weeks), citing an unwillingness to continue fol- low-up examinations/photographs. Thus, 18 of the 20 participants with culture-proven onychomycosis completed the 48-week study period. Five of the 18 participants who completed the study were seen at every follow-up period and had photographs taken at 4, 8, 12, 24, 36, and 48 weeks. The remaining 13 participants attended the major- ity of follow-up appointments (average missed ap- pointments � 1.8). Most missed appointments (16 of 23) were in the 4- or 8-week follow-up period; 6 were in the 12-week period; and 1 was in the 36-week period. At each follow-up visit, queries about compliance and use patterns (1–2 times per week, 3–5 times per week, or daily) showed that the majority of participants (15 of 18) reported daily application of the Vicks VapoRub and the remain- ing participants (3 of 18) reported use 3 to 5 times per week. The outcome data are presented in Table 1. Overall, 15 of the 18 participants (83%) had a positive response to the Vicks VapoRub treatment for onychomycosis. Five participants (27.8%) had a mycological cure (negative nail culture) at 48 weeks; 4 of these 5 showed complete clinical and mycological cures (22.2%). However, one still had evidence of dystrophic nail. Ten participants (55.6%) showed evidence of partial clinical cure (decreasing area of dystrophic nail); 9 of these had positive nail cultures at 48 weeks and one had a negative nail culture. The remaining 3 participants (16.7%) showed no significant clinical improve- ment through 48 weeks and had positive cultures at 48 weeks. Interestingly, all 18 participants rated their satisfaction with the appearance of the af- fected nail after the study course as either “very satisfied” (n � 9) or “satisfied” (n � 9). Photo- graphs of the observed changes in the toenails of three participants are presented in Figure 1. The average ratio of affected to total nail area decreased from 63% at initial evaluation to 41% at 48 weeks (P � .001; paired t test). Outcomes were better for the 5 participants with positive cultures for either Candida parapsilosis or T. mentagrophytes. All 5 of these participants showed complete clinical cure compared with none of the 13 participants with other organism growth (P � .001; Fisher’s exact test). Four of these 5 partici- pants also had negative cultures by the end of the study compared with one of the 13 remaining par- ticipants (P � .008; Fisher’s exact test). All 5 par- ticipants with positive cultures for either C. parap- silosis or T. mentagrophytes where also highly satisfied with treatment compared with only 4 of the 13 remaining participants (P � .029; Fisher’s exact test). Although these findings indicate a strong association between the organism and the success of treatment, they should be considered preliminary because they do not correspond to any preplanned hypothesis. Discussion We demonstrated in this pilot study that Vicks VapoRub provides a positive effect in the treat- ment of onychomycosis. This is the first clinical study in the literature to describe this finding. To date, treatment for onychomycosis is accom- plished primarily with oral (cure rates, 48% to 76%) and/or topical (34% cure rate with ciclopirox 8%)8,9 The cost for a complete course of oral med- ication treatment for onychomycosis ranges from $780 to $900 (not including associated costs for laboratory monitoring); a course of treatment with ciclopirox 8% is approximately $200.15 A 1-year course of Vicks VapoRub, by comparison, can be expected to cost approximately $24 to $36 (the cost of 2 to 3 6-ounce jars). Key weaknesses if this study include the small sample size, the lack of a control group, and vari- ability in the pathogens, as well as the initial degree of nail involvement between participants. These doi: 10.3122/jabfm.2011.01.100124 Treatment of Onychomycosis using Mentholated Ointment 71 o n 5 A p ril 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://w w w .ja b fm .o rg / J A m B o a rd F a m M e d : first p u b lish e d a s 1 0 .3 1 2 2 /ja b fm .2 0 1 1 .0 1 .1 0 0 1 2 4 o n 5 Ja n u a ry 2 0 1 1 . D o w n lo a d e d fro m http://www.jabfm.org/ Ta bl e 1. Pa rt ic ip an t D em og ra ph ic s, Cu lt ur e O rg an is m ,P ho to gr ap hi c As se ss m en t of Pe rc en ta ge of N ai l Af fe ct ed In it ia ll y an d at 12 -W ee k In te rv al s, Fi na l Cl in ic al an d M yc ol og ic al Cu re ,a nd Sa ti sf ac ti on P ar ti ci pa nt Se x A ge (y r) O rg an is m In it ia l A m ou nt A ff ec te d (% ) A ff ec te d at 12 W ee ks (% ) A ff ec te d at 24 W ee ks (% ) A ff ec te d at 36 W ee ks (% ) A ff ec te d at 48 W ee ks (% ) C lin ic al C ur e M yc ol og ic al C ur e Sa ti sf ac ti on * 1 M al e 68 F un ga l el em en ts 61 58 64 – 45 P ar ti al N o 2 2 M al e 76 C ry pt oc oc cu s la m en ti i 98 82 46 48 54 P ar ti al N o 1 3 M al e 30 T ri ch op hy to n ru br um 72 57 92 47 51 P ar ti al N o 2 4 M al e 37 T . ru br um 35 – 24 18 12 P ar ti al Y es 2 5 F em al e 52 C an di da pa ra ps ilo si s 44 22 22 25 27 P ar ti al N o 1 6 M al e 49 T . ru br um 70 50 60 44 47 P ar ti al N o 2 7 M al e 47 F un ga l el em en ts 59 – 45 64 47 P ar ti al N o 2 8 F em al e 31 T . ru br um 39 – 37 49 48 N o ch an ge N o 2 9 F em al e 37 C . pa ra ps ilo si s 37 – 17 11 4 C om pl et e Y es 1 10 F em al e 52 C . pa ra ps ilo si s 54 50 37 14 11 C om pl et e Y es 1 11 F em al e 85 P en ic ill iu m sp . 10 0 – 91 93 95 N o ch an ge N o 2 12 F em al e 45 T ri ch op hy to n m en ta gr op hy te s 20 – 15 9 5 C om pl et e N o 1 13 F em al e 69 F us ar iu m sp . 10 0 87 92 91 80 P ar ti al N o 2 14 M al e 54 T . ru br um 89 90 72 79 70 P ar ti al N o 1 15 M al e 40 T . ru br um 89 84 93 83 79 P ar ti al N o 1 16 M al e 57 C an di da al bi ca ns 63 58 53 51 58 N o ch an ge N o 2 17 M al e 65 T . m en ta gr op hy te s 84 71 41 20 7 C om pl et e Y es 1 18 F em al e 32 T . m en ta gr op hy te s 16 11 7 5 5 C om pl et e Y es 1 *1 � ve ry sa ti sfi ed ; 2 � sa ti sfi ed . 72 JABFM January–February 2011 Vol. 24 No. 1 http://www.jabfm.org o n 5 A p ril 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://w w w .ja b fm .o rg / J A m B o a rd F a m M e d : first p u b lish e d a s 1 0 .3 1 2 2 /ja b fm .2 0 1 1 .0 1 .1 0 0 1 2 4 o n 5 Ja n u a ry 2 0 1 1 . D o w n lo a d e d fro m http://www.jabfm.org/ weaknesses underscore the fact that this study does not prove or disprove the clinical utility of this unorthodox treatment of onychomycosis. Nevertheless, the strength of this study is found in the simplicity of its design; we provided a relatively inexpensive and innocuous therapy with straightforward instructions for use and then measured for effect through objective cul- ture and clinical appearance. Although inherently subjective, we believe the assessment of clinical appearance to be an important outcome measure. Nail fungal culture has good specificity and pos- itive predictive value (�94%), but the sensitivity is poor (30% to 50%).7 Photoshop CS3 software allowed for measurement of the area ratio of clinically affected (dystrophic) nail to the total nail. Although an unvalidated method of measur- ing the degree of infection in the nail, it was useful in providing a more objective means of estimating effect and change in clinical appear- ance. The participants’ positive satisfaction rat- ings with the treatment irrespective of the final clinical outcome shows that there is potential benefit in providing this simple, innocuous treat- ment even with unproven or partial efficacy. Future studies may benefit from grouping by the pathogens isolated. In the current study we enrolled 3 participants with cultures positive for C. parasilosis and 3 with cultures positive for T. mentagrophytes. These 6 participants accounted for all 5 of the complete clinical cures (one par- ticipant with the C. parapsilosis organism had a partial cure). In contrast, of the 6 participants with cultures positive for T. rubrum, 5 had a partial cure and 1 had no change. Focusing future treatment studies on specific organisms may pro- vide more details about treatment efficacy. Addi- tional areas for future studies may include com- bining Vicks VapoRub with other medical and physical modalities (filing/clipping) or compar- ing efficacy based on the degree of nail involve- ment (mild vs severe). Figure 1. Serial photographic assessment of clinical onychomycosis in selected participants. Discussion: - Topical treatment for onychomycosis have shown mixed/incomplete efficacy through limited trials - This small pilot trial shows similar mixed results however there is probable monetary advantage, ease of rx/instruction at primary care level – ease of maintenance treatment - Potential role as adjuvant rx to oral to help to reduce recurrence - May be more efficacious for specific pathogens - Weakness of study – small sample group, variability in pathogens, nail involvement Discussion: Discussion: Participant 2 – initial 24 weeks 48 weeks – no mycological cure partial clinical cure, ‘very satisfied’ Participant 17 – initial 24 weeks 48 weeks – mycological and clinical cure, ‘very satisfied’ Participant 9 – initial 24 weeks 48weeks – mycological and clinical cure, ‘very satisfied’ doi: 10.3122/jabfm.2011.01.100124 Treatment of Onychomycosis using Mentholated Ointment 73 o n 5 A p ril 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://w w w .ja b fm .o rg / J A m B o a rd F a m M e d : first p u b lish e d a s 1 0 .3 1 2 2 /ja b fm .2 0 1 1 .0 1 .1 0 0 1 2 4 o n 5 Ja n u a ry 2 0 1 1 . D o w n lo a d e d fro m http://www.jabfm.org/ Conclusion In this pilot study, Vicks VapoRub seemed to have some clinical effect in treating onychomycosis, par- ticularly when C. parapsilosis and T. mentagrophytes were the infecting organisms. Regardless of clinical effect, participants were highly satisfied with the simple, innocuous treatment strategy of once-daily application of Vicks VapoRub to the affected nail. Vicks VapoRub may represent a significant addi- tion to the clinical options for treating onychomy- cosis, not only because of its clinical effect but also because of the minimization of side effects and its lower cost compared with established therapies. Such a treatment might be a viable first-line option for a condition with limited morbidity apart from cosmetic effect. Future studies are required for proof of efficacy and better delineation of treat- ment effects. References 1. Gupta AK, Jain HC, Lynde CW, et al. Prevalence and epidemiology of onychomycosis in patients vis- iting physicians’ offices: a multicenter Canadian sur- vey of 15,000 patients. J Am Acad Dermatol 2000; 43:244 – 8. 2. Erbagci Z, Tuncel A, Zer Y, Balci I. A prospective epidemiologic survey on the prevalence of onycho- mycosis and dermatophytosis in male boarding school residents. Mycopathologia 2005;159:347. 3. Ghannoum MA, Hajjeh RA, Scher R, et al. A large- scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distri- bution, and antifungal susceptibility patterns. J Am Acad Dermatol 2000;43:641– 8. 4. Gupta AK, Jain HC, Lynde CW, Summerbell RC. Prevalence of unsuspected onychomycosis in pa- tients visting dermatologists’ offices in Ontario, Canada: a multicenter survey of 2001 patients. Int J Dermatol 1997;36:783–7. 5. Elewski BE, Charif MA. Prevalence of onychomy- cosis in patients attending a dermatology clinic in northeastern Ohio for other conditions. Arch Der- matol 1997;133:1172–3. 6. Drake LA, Patrick DL, Fleckman P, et al. The im- pact of onychomycosis on quality of life: develop- ment of an international onychomycosis question- naire to measure patient quality of life. J Am Acad Dermatol 1999;41:189 –96. 7. de Berker D. Fungal nail disease. N Engl J Med 2009;360:2108 –16. 8. Gupta AK, Ryder JE, Johnson AM. Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis. Br J Dermatol 2004; 150:537– 44. 9. Gupta AK, Joseph WS. Ciclopirox 8% nail lacquer in the treatment of onychomycosis of the toenails in the United States. J Am Podiatr Med Assoc 2000;90: 495–501. 10. Vicks VapoRub might help fight toenail fungus. Consum Rep 2006;71:49. 11. Pinto E, Pina-Vaz C, Salgueiro L, et al. Antifungal activity of the essential oil of Thymus pulegioides on Candida, Aspergillus and dermatophyte species. J Med Microbiol 2006;55(Pt 10);1367–73. 12. Salgueiro LR, Pinto E, Goncalves MG, et al. Chem- ical composition and antifungal activity of the essen- tial oil of Thymbra capitata. Planta Med 2004;70: 572–5. 13. Pina-Vaz C, Goncalves Rodrigues A, Pinto E, et al. Antifungal activity of Thymus oils, and their essen- tial compounds. J Eur Aca Dermatol Vernerol 2004; 18:73– 8. 14. Ramsewak RS, Nair MG, Stommel M, Selanders L. In vitro antagonistic activity of monoterpenes and their mixtures against “toe nail fungus” pathogens. Phytother Res 2003;17:376 –9. 15. Lexi-Comp Reader version 2.4060407. Drug pricing information. Hudson, OH: Lexi-Comp, Inc.; 2006. 74 JABFM January–February 2011 Vol. 24 No. 1 http://www.jabfm.org o n 5 A p ril 2 0 2 1 b y g u e st. 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