Yes. In reviewing the early study findings and his own experience as a patient, this author says lasers have potential in the treatment of onychomycosis.
By John Mozena, DPM Onychomycosis is one of the most commonly diagnosed foot problems that podiatrists treat. Two to 3 percent of the population is known to have onychomycosis and this incidence increases to 15 percent for those between the ages of 40 to 60.1 Since that time, World War II and Vietnam as well as worldwide transportation have accelerated the rate of fungus infections in our country. The infection, which was at one time a rare occurrence, has became an epidemic and will probably become a pandemic in the future.2 In the past, the profession has considered onychomycosis to be a cosmetic problem. This has led many physicians to the false belief that they should monitor this infection but do not need to treat it. However, recent evidence has been to the contrary. Seventy-five percent of the people who have this infection exhibit psychosocial concerns.3 These people face the dilemma of not being able to go to the swimming pool, use a public shower or even wear open toe sandals. I had a patient who would not remove her socks during her honeymoon due to embarrassment from nail fungus. Particularly concerning is the fact that 48 percent of the people with onychomycosis have foot pain.3 The standard for diagnosing fungus infections is the KOH test, which unfortunately has many false negatives and positive results. Fungal cultures have a much higher specificity but their sensitivity rates are not great. The best technique for sensitivity is a histological biopsy with a periodic acid-Schiff (PAS) stain but this is very expensive. Clinical diagnosis is certainly acceptable for instituting a treatment plan but verifying the existence of fungus helps one utilize the correct modality.
An Overview Of The Established Treatment Options
Until recently, the options for onychomycosis treatment included debridement, topical medications, oral medications and surgical destruction of the nail and nail bed. While nail debridement can facilitate patient comfort via debulking of the nail and a more cosmetically pleasing appearance, debridement does not really treat the fungus. There are multiple topical medications but the only one with any proven efficacy is ciclopirox lacquer 8% (Penlac, Sanofi Aventis).4 It is capable of penetrating the nail bed and getting to the source of the infection. Multiple oral medications are available with terbinafine (Lamisil, Novartis) being the most potent agent with a cure rate around 34 percent. Unfortunately, recurrence rates of 22 percent are reported after drug therapy.5 The last option for treatment that exists for nail fungus is surgical destruction of the nail itself. Although this is a very effective treatment option, the cosmetic appearance and the fact that this can be a painful procedure makes many patients hesitate before moving forward with the procedure.6
What Promise Does Laser Treatment Hold?
Recently, the emergence of new technology has brought about another option for the treatment of onychomycosis. Podiatry is no stranger to laser surgery. Lasers have been in use for the last several years in our profession for warts, dermal lesions and matrixectomy of ingrown nails. The newest laser application in podiatry is the ablation of a fungus infection within a toenail. Utilizing very specific wavelengths, the newer lasers are able to cause photo damage and/or ablation of the fungus within the toenail. The two lasers that I believe have the greatest potential are the Noveon laser (Nomir Medical) and the PinPointe FootLaser (PathoLase). Early studies with these devices show high efficacy rates.7,8 The Noveon laser uses an infrared light, which causes inactivation of the fungus. The Noveon’s two very specific infrared wavelengths have the unique ability to cause photo damage to microbes at physiological temperatures that can kill them directly or sensitize them to destruction. The PinPointe FootLaser is currently undergoing a controlled multicenter study to evaluate its effectiveness. Early studies indicate a clinical response rate of 87 percent.8 There are other laser companies working on fungus destruction but those lasers rely on UVC light, which can have a higher cancer risk.9 The PinPointe FootLaser uses a single wavelength of light to cause destruction of the fungus cell specifically. The pinpoint laser light passes through the toenail without causing damage to the nail or surrounding skin. The laser has a proprietary pulsed beam that differentially abates pathogens versus healthy tissues, resulting in the inhibition of pathogen growth. The patients receive safe, quick treatment with no drugs, no anesthesia and very little or no pain. The PinPointe FootLaser reportedly has minimal risks or side effects.8 Both lasers are currently being reviewed by the FDA for onychomycosis treatment and their respective treatment protocols. While neither currently has been cleared for a specific onychomycosis indication, the preliminary studies are very promising. Studies have shown not only good efficacy for the lasers but a high safety profile and good adherence as well since only one or a few treatments are required.10 Having a medical procedure that one can perform in one session can provide an enormous cost savings since multiple visits are not necessary.
Sharing Insights From Personal Experience As A Patient
I personally have tried topical, oral and laser treatment on the toenails on my left foot. I found topical medication only mildly effective. Since my onychomycosis is moderate to severe, topical medication is not indicated. Although oral medication did clear my nail significantly, re-infection occurred over time. I again tried oral medication but I experienced pain and tenderness in my liver area. I feel this may have been a gall bladder issue. Finally, I tried the PinPointe FootLaser about one year ago. I found significant improvement, especially in my hallux nail. I believe another treatment may be required for a more complete clearing as laser protocols are continuing to develop. I also would not hesitate to have any further treatment with the PinPointe Foot Laser as any health risk seems to be almost nonexistent.
Podiatrists have always embraced new proven technologies over the last few decades. We have introduced into our practices joint implants, absorbable hardware, arthroscopes, endoscopes and many other innovations. Indeed, new technologies can make a major impact on the lives of our patients. Now we are getting a new tool that may either augment our treatment regimen for onychomycosis or perhaps completely replace it. We should not ignore this potentially invaluable tool but put it in our arsenal of treatment ideas. Over time, we may find that laser treatment for onychomycosis may become the standard of care for this pandemic we are facing. Dr. Mozena is in private practice at the Town Center Foot Clinic in Portland, Ore. He is a Fellow of the American College of Foot and Ankle Surgeons and is board certified in foot and ankle surgery. References 1. Charis MA, Elewski BE. A historical perspective on onychomycosis. Dermatological Therapy 1997; 3:43, 2. Elewski BE. Tinea pedis and tinea manuum. In: (Dermis JD, Ed) Clinical Dermatology, third edition, JB Lippincott Co., Philadelphia, 1993. 3. Drake LA, Scher RK, Smith EB, et al. Effects of onychomycosis on the quality of life. J Am Acad Dermatol 1998; 38(5 Pt 1):702. 4. Brenner MA, Harkless LB, Mendicino RW, et al. Ciclopirox 8% nail lacquer topical solution for the treatment of onychomycosis in patients with diabetes: a multicenter, open-label study. J Am Podiatr Med Assoc 2007:97(3):195-202. 5. Tosti A, Piraccini BM, Stinchi C, Colombo MD. Relapses of onychomycosis after successful treatment with systemic antifungals: a three-year follow up. Dermatology 1998; 197(2)162-166. 6. Joseph WS, Mozena JD. Podiatric approach to onychomycosis In: Scher RK. Daniel CR (eds) Nails: Diagnosis, Therapy, Surgery, third edition, Elsevier Saunders, Philadelphia, 2005, chapter 18, pp. 133-140. 7. Available from: www.nomirmedical.com/news1.pdf 8. Available from: www.patholase.com/news/multi-center-trial 9. Bornstein E. A review of current research in light based technologies for treatment of podiatric infectious disease states. JAPMA 2009; 99(4):348-52. 10. Mozena JD, Mitnick JP. Emerging concepts in treating onychomycosis. Podiatry Today 2009; 22(10):46-51. Editor’s note: For further reading, see the June 2004 Podiatry Today supplement “Managing Onychomycosis” or “Emerging Concepts In Treating Onychomycosis” in the October 2009 issue. To access the archives, visit www.podiatrytoday.com.
No. This author says a simple search of the literature fails to provide adequate support for lasers as an effective means of treating onychomycosis.
By Brent Haverstock, DPM, FACFAS As podiatric physicians, we all encounter onychomycosis on a regular basis with patients presenting with a complaint of pain or dissatisfaction with the appearance of their nails. Onychomycosis is a fungal infection of the toenails and fingernails that results in discoloration, thickening and splitting of the nails, and lifting of the nails from the underlying nail bed. The disease, which is most frequently caused by dermatophytes, has a high incidence within the general population, especially among older individuals. It has been estimated that onychomycosis affects 2 to 3 percent of the general population in the United States and 6.5 percent in Canada.1,2 The condition affects children much less commonly with an estimated prevalence at less than 2.6 percent.3 Males are more commonly affected than females. Those with diabetes mellitus have a higher incidence of the condition and the dystrophic nail can result in increased pressure.4 This pressure leads to subungual ulceration, which often requires a partial or complete digital amputation.5 There is also evidence to suggest that fungal infection of the foot is a risk factor in the development of lower limb cellulitis in individuals with diabetes.6 Onychomycosis may be caused by one of three classifications of fungi: dermatophytes, yeasts and non-dermatophyte molds. Dermatophytes represent the most common group isolated from nail cultures with Trichophyton rubrum or Trichophyton mentagrophytes as the infecting organism. Trichophyton rubrum originated in West Africa, Southeast Asia, Indonesia and Northern Australia and spread to Europe, North and South America in the late 19th and 20th centuries.7,8 Candida species have emerged as second-line pathogens. Onychomycosis due to Candida (candidal onychomycosis) occurs increasingly in individuals who have defective immunity.9 Such immunity can be consequential to aging, diabetes, vascular diseases, HIV infection and drug therapies such as immunosuppressive therapy and broad-spectrum antibiotics. Non-dermatophyte mold infections are becoming more prevalent with the Aspergillus and Fusarium species commonly isolated.10
What Are The Current Treatment Options?
Onychomycosis is a difficult condition to treat. There are multiple therapeutic modalities including surgical removal of the nail as well as chemical, topical and oral methods. Dermatophyte infection of the nails is very difficult to eradicate due to the hard, protective nature of the nail plate. Once infection has established itself in the underlying surface of the nail above the nail bed, treatment becomes very difficult. Advances in oral therapy have contributed to improved treatment outcomes for patients. Generally, oral therapy demonstrates better outcomes. However, patients often prefer topical treatment over oral medication once one informs them of the potential side effects and complications associated with oral antifungal therapy. While the risk of liver failure following the use of oral therapy is likely far less prevalent than the fear generated from the use of the medication, patients often reject the treatment as they consider the risk associated with the complication far worse than the condition itself. Ciclopirox nail lacquer (Penlac, Sanofi Aventis) is the only FDA approved topical medication in the treatment of onychomycosis. Topical antifungal nail lacquers can deliver the antifungal agent directly to the nail unit. A recent study evaluated patients with distal and lateral subungual toenail onychomycosis who used ciclopirox nail lacquer once daily for nine months.11 Every week, patients removed the nail lacquer using acetone. The investigator recorded clinical nail status, KOH examination and mycological cultures at baseline, three, six and nine months. Trichophyton rubrum was the most common pathogen. At the end of the study, good improvement to complete cure occurred in 13 of 36 patients (36 percent), 12 patients showed only mild to moderate improvement and 11 patients (31 percent) had no clinical improvement. Researchers noted no adverse effects throughout the treatment period. Researchers have also investigated photodynamic therapy (PDT) as a treatment modality for onychomycosis. This treatment uses a drug called a photosensitizer or photosensitizing agent and a particular type of light.12 When photosensitizers are exposed to a specific wavelength of light, they produce a form of oxygen that kills nearby cells.13 In vitro studies have demonstrated that Trichophyton rubrum is able to metabolize 5-aminolevulinic acid (ALA) to protoporphyrin IX and that photodynamic therapy leads to significant reduction in its growth.14 Researchers demonstrated that ALA-PDT provided a cure rate of 43.3 percent 12 months after treatment. This cure rate reduced to 36.6 percent 18 months after treatment.15 Combination therapy consisting of periodic nail debridement and the application of topical medication along with the use of an oral antifungal agent would provide the greatest rate of eradication of the infection.16-18
What The Literature Reveals About Laser Treatment
A search of the literature fails to provide evidence-based support for the use of laser treatment in the management of onychomycosis. While physicians and patients alike would welcome the prospect of a non-invasive treatment for the eradication of onychomycosis, there exists little research to substantiate the claims of the companies developing the technology and those in the medical community who have embraced this technology. This is not to say that research has not been completed. There are studies underway to determine if this is an effective treatment modality. Although laser energy can eliminate dermatophytes in vitro, the direct laser elimination of onychomycosis is not successful due to difficulties in selectively delivering laser energy to the deeper levels of the nail plate without collateral damage. One study utilized a femtosecond (fsec) infrared titanium sapphire laser to circumvent this problem by the nonlinear interactions of these lasers with biological media.19 This quality, combined with the deeply penetrating nature of the near-infrared radiation, allows elimination of deeply seeded nail dermatophytes without associated collateral damage. Researchers used nail cuttings obtained from patients with onychomycosis caused by T. rubrum and subjected the samples to fsec laser irradiation, using increasing laser intensities with the focus scan throughout the whole thickness of the nail specimen. Researchers evaluated the efficacy of the laser treatment via subculture and used scanning electron microscopy to determine if there was fsec laser-induced collateral damage.19 The study found that the fsec laser successfully inhibited the growth of the fungus in all samples examined.19 This suggests that T. rubrum-mediated onychomycosis may be treated by fsec laser technology.
Assessing The Preliminary Claims And Evidence On Emerging Lasers
Currently two lasers exist in the marketplace with the PinPointe™ FootLaser™ (PathoLase) and the Noveon laser (Nomir Medical). The PinPointe FootLaser, introduced in 2008, uses a patented laser technology to target the pathogens that cause onychomycosis. The manufacturer claims that PinPointe treats patients safely and quickly with no drugs, no anesthesia or pain. PinPointe’s laser light reportedly passes through the toenail without causing damage to the nail or surrounding skin. Following the procedure, the new nail will reportedly grow in healthy and clear, according to the manufacturer. The laser lacks a specific indication for onychomycosis at the present time. A study of a small group of patients with onychomycosis indicated a potential efficacy rate with the PinPointe FootLaser as high as 87 percent.20 Currently, there is an ongoing multicenter trial evaluating the PinPointe Foot Laser for onychomycosis. The Noveon laser is a device which employs two distinct, near infrared wavelengths (870 nm and 930 nm) that are known to cause cellular photodamage via an endogenous reactive oxygen species mechanism of action in the absence of exogenous dyes or chemicals. Researchers have demonstrated photoinactivation of the fungi that causes onychomycosis when they have used the Noveon laser at safe energy densities in vitro and in vivo at physiologic temperatures.21 Human studies with the Noveon laser have met the published criteria for calculating the individual maximum safe radiant exposure (IMSRE) for human phototherapy as researchers reported no negative interactions in either the onychomycosis or MRSA IRB-approved studies.22,23
Until such time that researchers perform a randomized double-blinded trial comparing a laser to a placebo in the treatment of onychomycosis, its use should be guarded and patients should consider the treatment experimental. In the age of advancing medical technology, we as physicians must resist the claims of companies promoting the advantages of their products and only subject our patients to treatment that has withstood the scrutiny of a large independent clinical study. Like all practitioners who treat patients with onychomycosis, I hope such claims do eventually come to fruition. Dr. Haverstock is an Assistant Clinical Professor of Surgery and the Chief of the Division of Podiatric Surgery in the Department of Surgery at the University of Calgary. He is the Director of the Diabetic Foot and Limb Preservation Centre in Calgary. Dr. Haverstock is also a Fellow of the American Society of Podiatric Dermatology. References 1. Elewski BE. Clinical pearl: diagnosis of onychomycosis. J Am Acad Dermatol 1995; 32(3):500-501. 2. Vender RB, Lynde CW, Poulin Y. Prevalence and epidemiology of onychomycosis. Cutan Med Surg 2006; 10(Supp 2):528-33. 3. Ginter-Hanselmayer G, Weger W, Smoile J. Onychomycosis: a new emerging infectious disease in childhood and adolescents. Report on treatment experience with terbinafine and itraconazole in 36 patients. J Eur Acad Dermatol Venerol 2008; 22(4):470-475. 4. Gupta AK, Konnikov N, MacDonald P, et al. Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey. Br J Dermatol 1998;139(4):665-71. 5. Mayser P, Freund V, Budihardja D. Toenail onychomycosis in diabetic patients: issues and management. Am J Clin Dermatol 2009; 10(4):211-220. 6. Bristow IR, Spruce MC. Fungal foot infection, cellulitis and diabetes: a review. Diabet Med 2009; 26(5):548-51. 7. Iorizzo M, Piraccini BM, Tosti A. New fungal nail infections. Curr Opin Infect Dis 2007; 20(2):142-145. 8. Brody N. Cutaneous fungal infections: innovative treatment schedules with systemic agents. Int J Dermatol 1995; 34(4):284-289. 9. Jayatilake JA, Tilakaratne WM, Panagoda GJ. Candidal onychomycosis: a mini-review. Mycopathologia 2009; 168(4):165-73. 10. Shemer A, Davidovici B, Grunwalkd MH, Trau H, Amichal B. New criteria for the laboratory diagnosis of nondermatophythe moulds in onychomycosis. Br J Dermatol 2009; 160(1):37-39. 11. Shemer A, Nathansohn N, Trau H, et al. Ciclopirox nail lacquer for the treatment of onychomycosis: an open non-comparative study. J Dermatol 2010; 37(2):137-139. 12. Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature Reviews Cancer 2003; 3(5):380-7. 13. Wilson BC. Photodynamic therapy for cancer: principles. Can J Gastroenterol 2002; 16(6):393-6. 14. Kamp H, Tietz HJ, Lutz M, et al. Antifungal effect of 5-amilolevulinic acid PDT in Trichophyton rubrum. Mycoses 2005; 48(2):101-107. 15. Watanabe D, Kawamura C, Masuda Y, et al. Successful treatment of toenail onychomycosis with photodynamic therapy. Arch Dermatol 2008; 144(1):19-21. 16. Baran R, Hay RJ, Garduno JI. Review of antofungal therapy and the severity index for assessing onychomycosis: part I. J Dermatol Treat 2008; 19(2):72-81. 17. Takahata Y, Hiruma M, Shiraki Y, et al. Treatment of deramtophyte onychomycosis with three pulses of terbinafine (500 mg day for a week). Mycoses 2009; 52(1):72-76. 18. Jaiswal A, Sharma RP, Garg AP. An open randomized comparative study to test the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in the treatment of onychomycosis. Indian J Dermatol Venereol Leprol 2007; 73(6):393-6. 19. Manevitch Z, Lev D, Palhan M, Lewis A, Enk CD. Direct antifungal effect of femtosecond laser on Trichophyton rubrum onychomycosis. Photochem Photobiol (Epub ahead of print). 20. Harris DM, McDowell B, Strisower J. Laser treatment for toenail fungus. Proc SPIE 2009; 7161A:1-7. 21. Bornstein E. A review of current research in light-based technologies for the treatment of podiatric infectious disease states. JAPMA 2009; 99(4):348-352. 22. Bornstein ES, Robbins AH, Michelon M. Photo-inactivation of fungal pathogens that cause onychomycosis in vitro and in vivo with the Noveon dual wavelength laser system. Abstract presented at New Cardiovascular Horizons, September 10-13, 2008, New Orleans. 23. Bornstein ES. Treatment of onychomycosis using the Noveon dual-wavelength laser. FDA pivotal study data presented at the Council for Nail Disorders 13th Annual Meeting, March 5, 2009, San Francisco.