Clinical Dermatology

Griseofulvin is an orally administered antibiotic that provides effective treatment for most dermatophyte fungal infections. Absorption of griseofulvin from the gastrointestinal tract is less than ideal, but it can be enhanced when particle size is decreased during the manufacturing process. Two forms of griseofulvin are in current use. The first is called “microsized” and is the form of griseofulvin used when a prescription for the generic product is written. Dosage with this form of griseofulvin is generally 1.0 g/ day, divided into a morning and evening dose taken with meals. The second utilizes an even smaller particle size, which has been suspended in polyethylene glycol (Gris-PEG, Fulvicin PIG). The recommended dosage with these products is 500 to 750 mg/day. Griseofulvin is delivered to the stratum corneum via transepidermal water loss and through the deposition of sweat containing griseohllvin on the surface of the skin. Concentration of the drug in the stratum corneum is thus higher than can be obtained in the plasma.

Systemically administered griseofulvin can be used in all cases of tinea capitis, fungal folliculitis in areas other than the scalp, and onychomycosis; topical antifungal therapy is not etlixtive for these three conditions. Griseofulvin is also useful in instances of tinea corporis that are too extensive for topical therapy. Griseofulvin is not effective in the treatment of cutaneous yeast infections such as candidiasis or pityriasis (tinea) versicolor, nor is it effective in the treatment of systemic hmgal infections.

Griseofulvin has an unjustifiably bad reputation for the frequency and severity with which side effects occur. Gastrointestinal upset and headaches develop in about 10% of patients, but they are usually not severe enough to warrant discontinuation of the medication. Urticaria occurs in 1 % or 2% of patients; this does require discontinuation of use. Photosensitivity eruptions, proteinuria, and leukopenia occur with great rarity. Most clinicians do not obtain urine and blood tests for patients taking griseofulvin for less than 3 months. Griseofulvin is contraindicated in patients with all types of porphyria and should be used with extreme care in patients taking warfarin-like anticoagulants.

Ketoconazole represents a great advance in the treatment of fungal and yeast infections. Advantages include greater efficac)’ in resistant dermatophyte infections, effectiveness against yeast as well as dermatophyte infections, and once daily dosage. Unfort­unately, these are partially olfset by its very high cost, interaction with other medications, potential for significant hepatoxicity, and steroid-like and antiandrogenic properties when taken in high doses. As a result, it probably represents the systemic treatment of choice only for griseofulvin-resistant infections, short-term therapy for pityriasis (tinea) versicolor, some systemic fungal diseases, and unusual cases of onychomycosis.

Ketoconazole obtains its antifungal effect by interfering with the integrity of the fungal cell walls. It is generally given for cutaneous infections in a single morning dose of 200 mg. Rarely, twice that dose will be required. Long-term administration such as would be required for routine nail infections is discouraged because of some remaining concern over toxicity.

Fluconazole (Diflucan) is a new triazole antifungal agent related to ketoconazole. It is currently approved for treatment of severe candidal infections only, but it is also an effective agent for dermatophyte fungal infections. It appears to be appreciably safer than ketoconazole, but this advantage is currently offset by its extremely high price.

Itraconazole is another new triazole that has just been released in the United States. It is extremely effective against dermatophyte infections; its use in onychomycosis results in a cure rate roughly twice that for griseofulvin. It is also effective against sporotrichosis.

Terbinafine is a member of the allylamine family, but unlike naftifine, it is suitable for both topical application and oral administration. It is an extremely effective agent against dermatophytes and appears to be quite safe. Release in United States is expected shortly.

Flucytosine and amphotericin B are antifungal agents that are rarely used by dermatologists. These agents are not discussed here, therefore.

This entry was posted on Thursday, February 19th, 2009 at 4:45 am and is filed under Skin Disorders. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.