Onychomycosis
Onychomycosis is a progressive, recurring fungal infection that originates in the nail bed and may account, directly and indirectly, for up to 50% of all toenail abnormalities. Usually, the entry is between the hyponychium and the nail plate. The infection progresses to the nail, resulting in the typical appearance of yellowing and thickening of the nail. A mycotic infection of one or more of the toenails is often preceded by or accompanied by tinea pedis (athlete’s foot).
Although many people consider this primarily a cosmetic problem, a portion of the patients also experience pain (36%–48%) or limited mobility (41%) as a direct result of onychomycosis. Pressure necrosis from the nail bed or severe bacterial infections can even cause limb-threatening complications in older patients. The greatest predisposing factors are increasing age and male sex; men are 1.7 to 3.0 times more likely to have a fungal infection than women. Patients with vascular disease or diabetes, as well as immunocompromised patients (e.g., patients infected with human immunodeficiency virus [HIV]), also have a higher incidence of onychomycosis than the general population. With the effectiveness of the newer antifungal agents, diagnosis and treatment are more efficacious. Zaias has classified onychomycoses into four categories. Distal subungual onychomycosis primarily involves the distal nail bed and hyponychium, with secondary involvement of the undersurface of the nail plate. Proximal subungual onychomycosis describes the scenario when organisms enter from the posterior nail fold migrating to the matrix and nail plate ultimately. White superficial onychomycosis infects the surface of the nail by such organisms as Trichophyton mentagrophytes and by Aspergillus species. Candidal onychomycosis involves the entire nail plate and is caused by Candida albicans and other species.
Onychomycosis is a common disorder of the nail, present in possibly 20% of the population. The prevalence may be much higher than this, but culture or biopsy is not usually done. In patients older than 60 years, involvement can approach 75% of the population. Infection with dermatophytes, such as Trichophyton rubrum, T. entagrophytes, and Epidermophyton floccosum, is much more common than with Candida species. Nondermatophytes account for less than 1% of cases of onychomycosis. More typically, Candida is the cause of infection in children.
With chronic infection, the nail plate thickens and becomes discolored, brittle, and deformed. A buildup of chronic debris beneath the nail plate occurs over time. The thickened nail plate can become detached from the underlying nail bed and become painful when compressed by tight stockings or a constricting toe box.
Distal subungual onychomycosis. Distal subungual onychomycosis is the most common of the four types of mycotic infections . This deeply seated form of onychomycosis results in yellowish longitudinal streaks within the nail plate. Although the incubation period is unknown, the mode of transmission is thought to be through direct contact of a traumatized nail predisposed to mycotic infection. Serologic and genetic analysis of histocompatibility leukocyte antigen (HLA) class I in a homogeneous population showed that persons lacking the HLA-DR53 phenotype were at increased risk for developing Trichophyton rubrum onychomycosis. Therefore, HLA-DR53 might provide the immune response necessary to prevent a fungal infection.
The disease often occurs before the sixth decade of life. The infectious organism invades insidiously from the free edge of the nail plate toward the base, resulting in a thickened, discolored, and deformed nail plate. The initial infection occurs in the stratum corneum, the superficial layer of the epidermis. As the inflammation continues, the response of the nail bed is cellular accumulation, nail elevation, and discoloration. With the accumulation of debris beneath the nail, further fungal and microorganism growth occurs. After invading the nail bed, the fungus penetrates the nail plate and causes delamination of the toenail
Several dermatophytes are associated with subungual onychomycosis. Trichophyton, Epidermophyton, and Microsporum are the usual dermatophytes, and T. rubrum is the most common. Trichophyton interdigitale and T. mentagrophytes can also be present, and E. floccosum and nondermatophytes (Scopulariopsis, Aspergillus, Fusarium, and Candida species) have been reported. This disease entity is not thought to be contagious.
Endonyx onychomycosis is a variant of distal subungual onychomycosis in which the fungi reach the nail via the skin but invade the nail plate directly instead of infecting the nail bed.Endonyx onychomycosis does not cause hyperkeratosis. Despite the milky-white
discoloration of the nail, the nail plate itself is of normal thickness and smooth.
White superficial onychomycosis. White superficial onychomycosis appears as opaque, white, well-demarcated islands on the surface of the nail plate. In this infection, the pathogen invades the superficial dorsal aspect of the nail plate, which results in the development of white plaques. This is the rarest form of onychomycosis and is seldom seen except in immunologically compromised patients. The infection typically starts in the pericuticle nail plate and then grows distally, involving and destroying the entire nail plate. These plaques of localized fungal growth can progress to more diffuse involvement, invading the entire surface of the nail plate. The toenail can turn brownish and become roughened and pitted from chronic infection. The most common infectious organism is T. mentagrophytes. Topical antiseptics may be an effective early treatment for this type of onychomycosis.
Proximal subungual onychomycosis. Proximal subungual onychomycosis occurs infrequently and is typified by whitish discoloration extending distally from underneath the proximal nail fold. T. rubrum is the most usual infectious organism. This entity is more common in people infected with HIV.
Candidal onychomycosis. Candidal onychomycosis, characterized by generalized thickening of the nail plate, results from Candida albicans or Candida parapsilosis infection . Initially, longitudinal white striations appear within the nail plate. The nail bed thickens, and the distal end of the digit appears bulbous and clubbed. The nail plate can become opaque as well.
Diagnosis. An early sign of mycotic infection is thickening of the distal and medial/lateral borders of the nail plate. The nails can become opaque, and discoloration can occur with chronic infection. The edges of the nail plate can erode, and partial or complete loss of the nail plate can occur. As time passes with advanced onychomycosis, it is difficult for the clinician to distinguish among the patterns of mycotic penetration of the nail plate. Although total dystrophic onychomycosis may be considered a separate class of onychomycosis, it is actually a progression of any of the above types, with involvement of the entire nail unit leading to possible permanent scarring of the nail matrix.
When a fungal infection is suspected, diagnosis may be attempted by examining a specimen under a light microscope. Vigorous scraping of the nail produces debris that can be moistened with a few drops of 10% KOH solution. Hyphae may be seen microscopically. Samples cultured on an appropriate medium can aid in the diagnosis. Although culturing finely ground nail material or debris from beneath the nail is the optimal method of making the diagnosis of onychomycosis, 30% of the results are false negatives. Furthermore, the sensitivity of direct microscopy with KOH is not foolproof because the procedure is affected by many variables, including the skill of the slide preparer, the microscope used, and the sampling technique. Other methods of diagnosis include staining nail clippings with periodic acid–Schiff stain (PAS), using in vivo confocal microscopy, and more recently PCR.A study to estimate and compare the cost-effectiveness and sensitivity of diagnostic tests found that PAS was the most sensitive test (99%), and KOH-CBE (chlorazol black E) was second most sensitive at 94%. However, KOH-CBE was more cost-effective. It is important, but not always easy, to distinguish onychomycosis from psoriasis. Beginning antifungal medication without a confirmatory diagnosis can be both futile and expensive; however, certain clinical findings may be highly suggestive of onychomycosis. A cross-sectional diagnostic study of 277 patients found that when dermatologists consider onychomycosis the most probable diagnosis and abnormal plantar desquamation (>25% of the sole) is present, treatment should be started without any further testing. Clinical diagnosis with presence of these signs was found to be as accurate as laboratory tests, with a positive predictive value of 81%.
Similarly, in another review of 169 patients with nail disease, 32% had positive findings for onychomycosis on both direct examination and culture, and 20% had positive findings on direct microscopy alone.The authors identified four historical and clinical diagnostic
features significantly correlated with positive mycologic results: a history of tinea pedis in the past year; scaling on one or both soles; white, crumbly patches on the nail surface; and an abnormal color of the nail.
Systemic treatment. In a cumulative meta-analysis that evaluated randomized, controlled trials of systemic antifungal agents for the treatment of onychomycosis, the cure rates with many antifungal drugs were similar. The overall cumulative average (} standard
deviation [SD]) for mycologic cure with these drugs was as follows: terbinafine (Lamisil), 76% (}3%); pulse-dosed itraconazole (Sporanox), 63% (}7%); continuous-dosed itraconazole, 59% (}5%); fluconazole (Diflucan), 48% (}5%); and griseofulvin (Fulvicin), 60% (}6%). For open studies, the rates were somewhat higher: terbinafine, 83% (}12%); pulse-dosed itraconazole, 84% (}9%); and fluconazole, 79% (}3%).
One open study evaluated the use of terbinafine for the treatment of T. rubrum nail bed onychomycosis. With pulse-dosed oral terbinafine, 39 of 42 patients (93%) were cured. However, only 10 of 17 (59%) were cured when terbinafine was given every 4 months. It was thought that this regimen would not only save money but also lower drug induced
side effects. This use, however, is still off-label. Another study comparing intermittent terbinafine versus continuous terbinafine found that continuous dosing is better. Two other studies suggest that both intermittent and continuous terbinafine treatment are better than pulsed itraconazole therapy. Also, terbinafine may produce a
lower recurrence than itraconazole.
One study reported on a relatively small number of patients with onychomycosis in high-risk groups (immunocompromised patients, patients with diabetes, and patients with HIV). In these groups, terbinafine was well tolerated and equally effective in patients in all risk.
groups. Another study supports terbinafine’s safety in patients taking antidiabetic, antihypertensive, and cholesterol-lowering agents, including statins.
Another study found terbinafine to be the most cost-effective drug whether used as a pulse, continuous, or in combinations with other agents. However, the authors recommended 3 months of continuous treatment. The least cost-effective were itraconazole, griseofulvin, and fluconazole. The topical nail lacquer ciclopirox was three times more expensive than the systemic treatments when evaluating total cost for a complete cure.170
With the use of all pharmacologic agents for treating onychomycosis, whether topical, oral, or parenteral, a frank discussion with the patient should cover side effects, including hypersensitivity, liver toxicity, gastrointestinal disorders, and cardiovascular effects. These drugs are contraindicated during pregnancy because of their teratogenic effects. Hepatotoxicity has been reported in patients, especially older ones, who have a history of liver dysfunction. Other adverse effects include nausea and vomiting, pruritus, abdominal pain, and idiosyncratic liver dysfunction. Elevated liver enzyme levels are uncommon but have been reported in approximately 1 in 10,000 patients.
A potential new systemic treatment for onychomycosis is oral posaconazole. However, the low cost of generic terbinafine has largely limited posaconazole use to patient’s intolerant to terbinafine.
Local treatment. Local therapy includes mechanical grinding and debridement of the thickened nail plate with a motorized device, curettage of the necrotic subungual tissue, and adequate trimming of the thickened nail plate. For many patients, simple debridement adequately relieves pain and discomfort without the need for surgical or pharmacologic intervention.
Topical treatment. There are only two topical brush-on treatments for onychomycosis approved by the U.S. Food and Drug Administration—ciclopirox (Penlac), available in a lacquer, and more recently efinaconazole (Jublia), available as a 10% solution. Ciclopirox
1% cream (Loprox), terbinafine 1% cream, and ketoconazole 2% cream (Nizoral) have also been used for topical treatment. Typically, these creams are applied twice daily to the involved toenail and surrounding soft tissue. Transungual delivery of terbinafine by iontophoresis in onychomycotic nails has been investigated. The permeation and load
of drug crossing the nail plate was enhanced significantly during iontophoresis,
by 37-fold, compared with passive delivery in toenails.
Some clinicians prefer avulsion of the thickened nail plate, debridement of the necrotic tissue, and treatment of the matrix and nail bed twice daily. Hettinger and Valinsky advocate nail avulsion to help reduce the overall duration of treatment. After nail avulsion, the area is treated with a thin layer of cream. Therapy is continued until the nail plate has regrown. The authors reported that all nails that grew back were free of mycotic infection. They reported a 96% success rate at an average of 11 months of follow-up. After removal of the infected nail plate, patient compliance was critically important to the overall
success rate.
Other topical treatments are available including mechanical, chemical, and photodynamic therapies. Chemical nail plate destruction, surgical ablation, or a terminal Syme amputation may be considered. These techniques are discussed elsewhere. In patients who are at risk
of adverse kidney or liver effects and medication interactions, such as children, the elderly, and patients with systemic diseases, photodynamic therapy may be an alternative.The use of laser therapy to eradicate the onychomycosis, both low-level (400–600 nM) and higher-level (800 nM) laser therapies is currently being used. A 2021 systematic review of laser therapy revealed a few randomized prospective trials and combined clinical cure rate of 13% to 26%. A prospective study of triple wavelength laser therapy and mechanical abrasion in 16 patients found clinical benefit but continued infection based on histopathologic examination in 100% of treated toes. A novel topical treatment of onychomycosis using Vicks VapoRub has been reported to have a positive clinical effect. This study reported 83% positive treatment effect and 27% having a mycologic and clinical cure at 48 weeks by applying the ointment to the affected nail two times a day.
Combination treatment: Topical, systemic, debridement. A combination of oral and topical antifungal agents has also been advocated. Use of concomitant amorolfine 5% nail lacquer with oral terbinafine resulted in improved cure rates, compared to terbinafine alone, in severe toenail onychomycosis. Another study also promoted use of topical agents in combination with a systemic antifungal agent, advocating improved cure rates of onychomycosis compared with oral therapy alone. It further suggested a triple therapy with the addition of debridement to
improve these results.
Source : Coughlin and Mann’s Surgery of the foot and ankle , 10 edition 2023