Finally, an end to the coverup?

Special to The Times

WHEN fungus invaded her toenails 10 years ago, Ruth Carsch of San Francisco didn’t care too much at first. Her nails became “thick and fat and yellow,” says the 61-year-old information specialist, but she could always hide that behind colorful nail polish.

What she really minded, she says, was how the nail plates grew so thick from the infection that they squashed the toes beneath. “My toes are much fatter than they used to be. My feet are wider,” Carsch says. “It seems to have deformed my toes.”

Her podiatrist suggested topical creams, but often they couldn’t reach the skin-loving fungus found on the skin underneath the nails. “Or they could take my toenails out,” Carsch says. “I wasn’t ready for that one.” She refuses to take either of the two antifungal pills available, she says, because her sister-in-law suffered a dangerous drug interaction after taking one of them.


Carsch has instead signed up to help test a new topical antifungal treatment. The hope is that the liquid medication, manufactured by Anacor Pharmaceuticals of Palo Alto, can penetrate toenails, reaching infections on the nail bed and eliminating fungus altogether.

More than 35 million adults in the U.S. have at least one nail -- usually a toenail -- that is infected with fungus, a condition known as onychomycosis or tinea unguium. Infection risk goes up with age; between 25% and 40% of people older than 40 are affected, according to the American Academy of Dermatology.

Infected nails rarely get better without treatment, says Raza Aly, professor of dermatology at UC San Francisco. According to some industry estimates, toenail fungus sufferers worldwide spend about $300 million on topical treatments and about $2 billion on oral antifungals each year.

Still, fungal nail infections appear to be on the rise in the U.S., Aly says. This includes a growing number of women, whose infection rates have traditionally lagged behind men’s. It’s still unclear exactly why more women are seeking treatment, but Aly suspects that new footwear fashions are to blame. “Women are catching up to men. Now they’re also wearing tennis shoes and other occlusive shoes for several hours a day,” he says.

For many sufferers, an infected toenail is nothing more than an embarrassing eyesore. But for others, it could lead to more dangerous conditions, says Dr. Richard Scher, a professor of dermatology at Columbia University. In patients with diabetes or with circulatory or immune system problems, for example, a fungal infection can more easily open the door to a bacterial infection in the skin or veins in the legs -- a condition more difficult to treat, especially in these patients.

Existing toenail fungus treatments aren’t perfect, Scher says. Two antifungal pills, terbinafine and itraconazole, work well in most people but have been known in rare situations to cause serious liver problems such as hepatitis. Plus, some patients, like Carsch, prefer to avoid oral treatments or cannot take them because of drug interactions.


ONLY one topical treatment, ciclopirox, is approved by the U.S. Food and Drug Administration for treating nail fungus. In a lotion, the drug works well for fungal skin infections -- athlete’s foot, for example -- but in a lacquer, its efficacy for a complete cure is only 5.5% to 8.5%, Scher says.

Now researchers at Anacor hope their new drug can go where others can’t. “We set about finding a molecule that not only acted against the organisms that cause onychomycosis but that also penetrated the nail and nail bed,” says Dr. Karl Beutner, chief medical officer at Anacor. The new drug -- a fungicidal, rather than a fungistatic like many current treatments -- is designed to kill fungus, not just slow its growth. Called AN2690 for now, it works by shutting down the fungus’ protein synthesis process, Beutner says.

The drug’s small molecules seem to absorb easily into the water-rich environment of toenails, Beutner says. In the lab, researchers applied AN2690 every day for two weeks to detached cadaver fingernails. They found that 16% of the solution seeped all the way through the nails -- 200 times the amount that a ciclopirox solution managed under the same circumstances.

Two Phase 2 clinical trials of AN2690 are underway in the U.S. and Mexico. Researchers are looking to see if patients treated with the drug will grow at least 5 millimeters of fungus-free nail over six months. Halfway through the study, preliminary results suggest that 13 out of 24 patients are on track to meet that criteria, showing at least 2.5 millimeters of clear toenail growth, Beutner says.

Other companies are also working to develop topical antifungal treatments. Novartis AG, in Basel, Switzerland, is designing clinical trials in the U.S. and Europe for a new topical treatment containing terbinafine, the same antifungal in its oral medication. And in January, MediQuest Therapeutics of Seattle started recruiting for a Phase 2 clinical trial to test terbinafine and naftifine -- an antifungal commonly used to treat athlete’s foot -- in a new type of gel designed to effectively penetrate the nail.

Carsch realizes that compared with other potential health problems, her thick yellow toenails aren’t so bad. The infection isn’t painful, and she hasn’t had any complications, she says. Still, it would be nice to have her old toes back.

“I can’t wear certain shoes,” she says. “I can’t wear cute little strappy sandals.”



How to put your best foot forward

What causes it?

The main culprit behind toenail infections is a type of fungus called dermatophyte, although mold and yeast cause a small percentage of cases.

“Dermatophytes love skin,” says Raza Aly, professor of dermatology at UC San Francisco. They eat keratin -- the protein found in toenails, fingernails and the top layer of the skin.

When these fungi launch a toenail infection, they usually do so by latching onto the keratin-rich seam between the toenail tip and skin beneath. Or they can cause athlete’s foot first, usually by infecting the web of skin between toes, and then move on to also infect nearby toenails. Don’t assume fungus will go away on its own.

“If one nail is infected, it can get into the second, third and so on, until all 10 toenails are affected,” Aly says.

Who’s at risk?

Although everyone can develop toenail fungus, some people are more susceptible than others.

About 1 in 5 people, for example, has an inherited susceptibility to infections from Trichophyton rubrum, a common dermatophyte.

Athletes are more likely to develop the fungus because they’re more likely to have bruised toenails, wear stuffy athletic shoes and spend time in warm, damp locker rooms -- all of which are risk factors.

Age brings structural changes to toenails, too, which in turn bring more infections. It’s why children are less likely to have the fungus, and elderly people more likely.

“Nails don’t grow as fast as when you were young,” Aly says. “Fast-growing nails can get rid of fungus faster.”

Family members of those with toenail fungus also may be at higher risk.

Researchers at Case Western Reserve University in Ohio recently conducted DNA analyses of toenail fungus in 57 families, in the hopes of learning how fungus can pass from foot to foot in a family. They found that in 18% of the households, a single infected individual spread toenail fungus to at least one other family member.

These results, which will be presented in more detail in September, may help physicians decide whether to recommend preventive treatment for people who live with a toenail fungus sufferer.

How can it be prevented?

Don’t go barefoot in high-risk areas, such as locker rooms and communal showers. People infected with toenail fungus or athlete’s foot may shed their skin scales onto the floor -- along with fungi that can remain active for days. They stick to damp skin, where they can multiply and spread.

Be sure to wash and dry your feet carefully. Keep your toenails trimmed to minimize bruising and trauma -- these provide an ideal environment for fungus to take hold.

Let your feet breathe. Fungus thrives in warm, stuffy, damp environments -- such as the insides of close-fitting shoes or hosiery.

Don’t use other people’s foot-care instruments. If you must, cleanse them with alcohol first.

Don’t share shoes.

See a doctor about toenail fungus if you have other health problems, such as diabetes or disorders that suppress your immune system.