Nail Fungus: Disfiguring and Difficult to Treat

According to U.S. Pharmacist, a leading trade journal published monthly, Onychomycosis is a leading cause of nail loss, which is not only unsightly, but can lead to functional limitations.

Onychomycosis is a general term referring to several fungal nail infections, such as those caused by dermatophytes, non-dermatophytes and yeasts. The condition was rare at one time, but its incidence has risen in the past decade. It now accounts for almost one-half of the total number of nail disorders. Fortunately, there are several therapeutic options available, although each has its own peculiar set of precautions.

Differential Diagnosis of Onychomycosis

Physicians are hard-pressed to be sure that a nail infection is due to fungal invaders, because such conditions as psoriasis, eczematous eruptions and senile ischemia duplicate its manifestations. White nails can also be caused by hypoalbuminemia, cirrhosis and striate leukonychia (white bands). To seal the diagnosis, the physician may confirm a fungal etiology by placing nail scrapings in a drop of potassium hydroxide 20% on a glass slide, covered with a cover slip. Gentle heating followed by examination at the microscopic level reveals fungal hyphae, which grow in a linear, branching fashion.

Types of Onychomycosis

Experts divide Onychomycosis into several subtypes. The most common is distal subungual Onychomycosis “DSO”, produced by Tinea Rubrum, which initially affects the upper corner of the nail bed beneath the nail. The patient with DSO invariably also has Tinea Pedis. Proximal Subungual Onychomycosis “PSO” is located on the proximal nail, next to the cuticle, and serves as a common marker of AIDS. A third subtype, White Superficial Onychomycosis, is a direct nail penetration caused by Tinea mentagrophytes, manifesting as white spots scattered over the nail surface that may join each other until the entire nail is affected. Tinea Unguium is the term reserved for the sub- type of Onychomycosis produced solely by dermatophytes, such as the Tinea that also cause athletes foot. For example, one patient contracted Onychomycosis as a result of contact with a cat infected with the common zoophilic dermatophyte Microsporum canis.

Epidemiology of Onychomycosis

Onychomycosis is most often found on the toenails of men and the fingernails of women. Risk factors for nail fungus include:

Increasing age: Overall, Onychomycosis is more common in adults than children. Investigators assert that the slowly advancing age of the population is the single reason behind the rise in incidents of Onychomycosis. However, the practitioner must also be alert to pediatric Onychomycosis. Researchers examined 100 patients in a pediatric dermatology department and discovered that Onychomycosis was the most common condition causing nail alterations. Fifty-four of the patients exhibited toenail fungus, twenty-five had the problem in the fingernails, and twenty-one had fungus in both toenails and fingernails.

Diabetes mellitus: In one study, researchers found DSO to be the second most common skin/nail infection in diabetic patients, most often due to Trichophyton mentagrophytes.

Impaired venous and lymphatic drainage: In one study of patients with chronic venous insufficiency, the frequency of Onychomycosis was 36.11%.

Poorly fitting shoes: Shoes that do not provide sufficient toe space can be another common cause of infection, especially among the most commonly infected toes, the “pinky” toe and the “big” toe.

Participation in sports: Warm, moist socks inside enclosed sneakers create an environment that is conducive to onchomycosis, which is why it is very common among athletes.

Manifestations of Onychomycosis

The patient with Onychomycosis initially notices a hyperkeratosis of the undersurface of the nail plate that affects the distal nail bed. The initial discoloration is usually yellow. The nail bed is not flat, but is composed of longitudinal folds. The fungus spreads laterally beneath the nail plate in those folds to produce spears of hyperkeratosis as Onychomycosis advances. The patient often attempts to improve the look of the nail by picking or manipulating it, but this does not help to any extent. As the infection proceeds, waste debris from the fungal growth accumulates beneath the nail, causing it to rise from the surface of the nail bed. Eventually it loosens to a considerable extent. The nail exhibits severe distortion and appears flaky, opaque, and crumbly.

Complete nail loss is unsightly. Although the cosmetic deformity is troubling, it is dwarfed by the resultant functional limitations. Loss of a fingernail compromises the patient's fine motor skills, such as picking up a pin or other small object from a flat surface. The large toenail (and, to a lesser degree, the other toe-nails) aids in the traction that allows walking. Loss of toenails can lead to pain upon ambulation, which may in turn cause the patient to alter the gait to prevent pain.

Treatment of Onychomycosis

In regard to prescription medications, griseofulvin was the standard for decades, but has fallen into disuse due to disappointing results. In one study, griseofulvin was to be taken for one year by subjects with Onychomycosis. The cure rate was only 23.8%, and the dropout rate was 52.6%. In the same study, patients given Itraconazole had a cure rate of 50% and a dropout rate of only 38.1%. A three-year follow-up demonstrated that most of the Itraconazole patients were cured, but 30% of the griseofulvin patients remained infected. Low-dose continuous Itraconazole therapy produced a final cure rate of over 90%. Itraconazole (Sporanox) may be administered in a dose of 200mg daily for 12 consecutive weeks for toenail infection without finger-nail involvement. If only fingernails are affected, the manufacturer recommends “pulse therapy" of 200mg orally twice daily for one week, followed by 3 weeks of no medication, finishing with one final pulse in the same regimen as the first. The product should be taken with a full meal to enhance absorption. It may increase the plasma concentrations of warfarin, vinca alkaloids, midazolam, triazolam, diazepam, lovastatin, simvastatin, cyclosporine, methyl prednisolone, digoxin and quinidine. The plasma concentration of Itraconazole may be lowered if patients are also ingesting phenytoin, Phenobarbital, carbamazepine, isoniazid, rifampin or rifabutin. Because of its superiority over griseofulvin, Itraconazole has become one of the two most commonly used Onychomycosis medications in the United States. The other is terbinafine (Lamisil) 250 mg tablets.

The manufacturer recommends continuous therapy of one tablet daily for 6 weeks for fingernail Onychomycosis or for 12 weeks for toenail Onychomycosis. The clearance of the medication is increased 100% inpatients taking rifampin.

The Latest FDA Advisory for Systemic Antifungals

The July-August 2001issue of FDA Consumer relayed the contents of an FDA health advisory announcing serious risks associated with Sporanox (Itraconazole) and oral Lamisil (terbinafine hydrochloride). When taken orally for such conditions as Onychomycosis, both Sporanox and Lamisil have been associated with serious hepatic problems that have resulted in liver failure, the need for a transplant, and death. Both will carry new labeling recommending that patients furnish a nail specimen for testing to confirm the presence of fungi before either is prescribed. Sporanox has also been associated with a small hut serious risk of developing congestive heart failure. One report summarized the details of 58 patients who developed CHF that may have been due to Itraconazole Newly required labeling will state that it should not be given to patients with nail infections if they have evidence of cardiac dysfunction. The agency suggested that patients or health professionals who have knowledge of adverse events associated with either drug call the FDA's Med Watch Program.

New Topical Nail Lacquer

The recent warnings regarding oral agents have made a new topical nail lacquer more attractive. Ciclopirox (Penlac) 8% topical solution appears to exert its antifungal effect through chelation of iron and aluminum. Fungal cells degrade peroxides within them through metal-dependent enzymatic reactions. When the enzymes are denied iron and aluminum, the result may be a lethal build-up of peroxides. In manufacturer-sponsored studies on patients with 20%-65% involvement of the nail plate of the large toe, Ciclopirox demonstrated ability to produce a clear nail and negative mycology in 6%9% (is it 6% or 9%?) of patients, whereas patients receiving placebo alone only cleared in less than 1% of cases. Negative mycology alone was achieved for 29%-36% of patients, as opposed to 9%-11%who received placebo. Ciclopirox solution is applied to affected fingernails and toenails and the surrounding skin. It is specifically indicated for mild/moderate infections that do not involve the lunula and that are due to Trichophyton Rubrum. A professional also must remove the unattached, infected nails as often as every month. Patients should not take oral antifungal medications concomitantly Patients are directed to apply Ciclopirox evenly to the entire nail plate and 5 mm of surrounding skin. If the nail is free of the nail bed, the patient should attempt to apply the product to the undersurface of the nail plate. A full course of therapy is considered to be 48 weeks. Nail polish should not be used during the course of therapy. Once weekly, the accumulated coatings should be removed with alcohol, and the patient should file and trim the nails.