White : Diseases of the Skin - Systemic Therapies

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Gary M. White & Neil H. Cox

Diseases of the Skin

4	Systemic Therapies

ANTIFUNGAL AGENTS

Systemic antifungal agents used in dermatology fall into several groups according to mode of action. The most commonly used for superficial mycoses interfere with ergosterol, a sterol of the fungal but not of the host cell walls. Topical agents (Ch.26) can be used for many infections; systemic agents are generally indicated for infection of nails, thick skin sites (Fig.4.4a), scalp and other hairy areas (Fig.4.4b), deeper or systemic infections, extensive disease (Fig.4.4b), failure of topical agents, or in immunosuppressed individuals. However, it is important to make a firm diagnosis by appropriate mycologic sampling (Ch. 26) before considering systemic therapy.

Figure 4.4 (a)Involvement of thick skin sites ( a ), hairy areas

Figure 4.4 (b),and extensive skin involvement

Figure. 4.4 (c)as shown here, are indications for systemic rather than topical antifungal therapy. Note that the palm involvement in (a) is unilateral, a typical feature of fungal infection of the hands. Pustules are common at hairy sites affected by athlete’s foot-type fungi, as in (b), although they are uncommon on the scalp in children affected by cat or dog ringworm. All three patients had Trichophyton rubrum infection, neglected in the patient shown in (c).

•	Azoles—these inhibit sterol demethylase to reduce ergosterol synthesis, and include imidazoles (e.g. ketoconazole) and triazoles (e.g. itraconazole).
•	Allylamines (e.g. terbinafine)—inhibit squalene expoxidase to reduce ergosterol synthesis.
•	Polyenes (e.g. amphotericin)—disrupt cell membranes.
•	Griseofulvin—blocks microtubules.
•	Flucytosine—inhibits DNA and RNA synthesis.

The commonest agents used for superficial infections are terbinafine (usually the most effective for dermatophyte infections), fluconazole (mainly used for candidal infection), and itraconazole (which has a wide spectrum of activity). Itraconazole is useful in pityriasis versicolor (Fig.4.5), and opinion varies as to whether it should be first-line therapy or used if topical treatment fails. Griseofulvin is used rather less in developed countries, as it is fungistatic and slower to work, but it is widely used worldwide, as it is much cheaper than the newer agents. Ketoconazole is used less often systemically than in the past, as it has been associated with hepatotoxicity and therefore requires closer monitoring.

Figure 4.5 Pityriasis versicolor, a yeast infection for which itraconazole is effective.

Side effects of the commonly used agents are generally few and mild, but azoles in particular have the potential for drug interactions with other medications that are metabolized by cytochrome P450. Taste disturbance is a feature with terbinafine, and provocation of discoid lupus erythematosus has been reported.