Novel Treatment of Onychomycosis using Over-the-Counter Mentholated Ointment: A Clinical Case Series

Methods

The study protocol was approved by the institutional 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 arrange an appointment with study investigators. During the initial appointment, the study was explained and informed consent for participation was obtained. Demographic data (age, sex, military status) was obtained along with historic data (duration of dystrophic nail, prior treatment for onychomycosis, 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. Exclusion criteria included any history of allergic sensitivity 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 photographic assessment of the nail; and a negative culture 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 instructed 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 contacted and removed from the study. Volunteers with positive cultures were contacted for follow-up assessments at 4, 8, 12, 24, 36, and 48 weeks. Repeat digital photographs, assessment for adverse reactions, treatment effect, patterns of VapoRub use, and the patient's perceived tolerability of treatment were performed/assessed during each visit.

The primary outcome measures for the study were mycological cure at 48 weeks, defined as negative 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. Photographic 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 measured was patient satisfaction with the appearance 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).

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 follow-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 majority of follow-up appointments (average missed appointments = 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 remaining 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 improvement through 48 weeks and had positive cultures at 48 weeks. Interestingly, all 18 participants rated their satisfaction with the appearance of the affected nail after the study course as either “very satisfied” (n = 9) or “satisfied” (n = 9). Photographs 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).

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Figure 1.

Serial photographic assessment of clinical onychomycosis in selected participants.

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 participants also had negative cultures by the end of the study compared with one of the 13 remaining participants (P = .008; Fisher's exact test). All 5 participants with positive cultures for either C. parapsilosis 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 treatment of onychomycosis. This is the first clinical study in the literature to describe this finding.

To date, treatment for onychomycosis is accomplished 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 medication 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 variability in the pathogens, as well as the initial degree of nail involvement between participants. These 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 culture 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 positive 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 measuring the degree of infection in the nail, it was useful in providing a more objective means of estimating effect and change in clinical appearance. The participants’ positive satisfaction ratings with the treatment irrespective of the final clinical outcome shows that there is potential benefit in providing this simple, innocuous treatment 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 participant 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 provide more details about treatment efficacy. Additional areas for future studies may include combining Vicks VapoRub with other medical and physical modalities (filing/clipping) or comparing efficacy based on the degree of nail involvement (mild vs severe).

Conclusion

In this pilot study, Vicks VapoRub seemed to have some clinical effect in treating onychomycosis, particularly 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 addition to the clinical options for treating onychomycosis, 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 treatment effects.