MedicineToday 2014; 15(6): 35-47 PEER REVIEWED FEATURE 2 CPD POINTS Therapies for common cutaneous fungal infections KENG-EE THAI MB BS(Hons), BMedSci(Hons), FACD Key points A practical approach to the diagnosis and treatment of common fungal • Fungal infection should infections of the skin and hair is provided. Topical antifungal therapies always be in the differential are effective and usually used as first-line therapy, with oral antifungals diagnosis of any scaly rash. being saved for recalcitrant infections. Treatment should be for several • Topical antifungal agents are typically adequate treatment weeks at least. for simple tinea. • Oral antifungal therapy may inea and yeast infections are among the dermatophytoses (tinea) and yeast infections be required for extensive most common diagnoses found in general and their differential diagnoses and treatments disease, fungal folliculitis and practice and dermatology. Although are then discussed (Table). tinea involving the face, hair- antifungal therapies are effective in these bearing areas, palms and T infections, an accurate diagnosis is required to ANTIFUNGAL THERAPIES soles. avoid misuse of these or other topical agents. Topical antifungal preparations are the most • Tinea should be suspected if Furthermore, subsequent active prevention is commonly prescribed agents for dermatomy- there is unilateral hand just as important as the initial treatment of the coses, with systemic agents being used for dermatitis and rash on both fungal infection. complex, widespread tinea or when topical agents feet – ‘one hand and two feet’ This article provides a practical approach fail for tinea or yeast infections. The pharmacol- involvement. to antifungal therapy for common fungal infec- ogy of the systemic agents is discussed first here. • Oral antifungal treatments tions of the skin and hair. It is not intended to can often be pulsed inter mit- be an in-depth treatise on derma tomycoses, Systemic antifungal agents tently, reducing the overall and onychomycosis and cutaneous candidiasis Terbinafine dose required. are not covered in detail. The initial section Terbinafine is a highly effective antifungal agent, briefly reviews the practical pharma cology of by virtue of its fungicidal property. It is an ally- commonly used antifungal agents, in order to lamine and works by inhibiting squalene epoxi- guide their use. The defining features of various dase. It has greater affinity for fungal squalene Dr Thai is a Consultant Dermatologist and Visiting Medical Officer at the Epicutaneous Patch Testing Clinic and Hair Copyright _Layoutand 1 Nail17/01/12 Clinic, Prince 1:43 PM of Wales Page Hospital, 4 Randwick; a Visiting Medical Officer at the Macquarie University Hospital, © GETTY IMAGES/SPL CREATIVE Macquarie Park; and in private practice in Gordon, Sydney, NSW. MedicineToday x JUNE 2014, VOLUME 15, NUMBER 6 35 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2014. TREATING COMMON FUNGAL INFECTIONS CONTINUED epoxidase than the human type. Inhibition interactions and there are no contraindi- may reduce absorption of griseofulvin; they results in a deficiency of ergosterol (an impor- cations to its use with other drugs. How- should be taken two hours after the anti- tant fungal cell wall constituent) and the ever, because it is an inhibitor of cytochrome fungal agent. Griseofulvin can increase the accumulation of squalene, both of which P450 2D6, care should be taken when metabolism of warfarin and the contra- disrupt fungal cell membranes. It is especially administering it to patients taking tricyclic ceptive pill. When co-administered with effective against infections caused by der- antidepressants and other drugs metabo- alcohol, patients should be warned about matophytes (Epidermophyton, Micro- lised by this isozyme. the disulfiram-like reaction that can occur. sporum and Trichophyton). About 80% of an oral dose of terbinafine Griseofulvin Itraconazole is absorbed, regardless of food intake, but Griseofulvin was the first important oral Itraconazole, a triazole, is useful in the first-pass metabolism limits bioavailability antifungal agent available for the treat- treatment of onychomycosis and dermato- to 40%. Terbinafine is lipophilic and thus ment of fungal skin infections. Histori- mycoses. It is also useful for infections widely distributed, with significant and cally its main use was in the treatment of caused by Candida, Malassezia and some rapid distribution in skin stratum cor- tinea capitis. Being only fungistatic, it nondermatophyte moulds. It acts by inhib- neum, sebum, hair and nails. is not as effective as the other agents iting 14α-demethylase, resulting in inhi- High concentrations of the medication described here. bition of ergosterol production from are reached in the stratum corneum within Treatment needs to be continuous until lanosterol. hours of commencement of therapy. After mycological and clinical cure when gri- Being a highly lipophilic drug, itracona- 12 days of terbinafine 250 mg per day, there seofulvin is used to treat dermatophyte zole is best taken with a meal. A low pH is enough drug in the skin to maintain a infections. This often leads to protracted gastric environment is also useful to aid minimum inhibitory concentration (MIC) courses (several weeks to months), espe- absorption. In patients who have relative for two to three weeks after cessation of cially with onychomycosis, for which up achlorhydria (i.e. those taking H2-antago- treatment. Terbinafine is found in the dis- to 18 months of treatment may be required. nists, proton pump inhibitors or antacids) tal nail after one week of therapy, and after It is important to note that griseofulvin or who are taking the drug on an empty six or more weeks of treatment it is detect- has no activity against the yeasts Candida stomach, absorption is aided by the able for at least another 30 weeks (indicat- and Malassezia (formerly known as co- administration of a cola soft drink. The ing the potential for continued action). It Pityrosporum). drug is often used in a pulsatile manner. is also found in the hair after one week of Typical doses in children are 10 to Itraconazole rapidly presents into the treatment, and may be detected for up to 15 mg/kg daily, with recalcitrant cases stratum corneum and persists for three to another 50 days after just two weeks of requiring up to 25 mg/kg daily, and in four weeks after cessation of therapy. In treatment. adults, 500 mg to 1 g daily. The medication the nail, a MIC is achieved after only one As terbinafine is metabolised in the liver is best taken with a fatty meal to increase week of 200 mg itraconazole twice a day. and the metabolites are excreted in the absorption. For children, the tablets can be After several one-week-per-month pulses urine, dose adjustment is required in crushed and administered with, for exam- of treatment, the drug can persist for patients with renal failure where the serum ple, chocolate, full-cream ice cream or months in the nail plate. Appreciable creatinine level exceeds 300 µmol/L. With peanut butter. The medication is presented amounts are present in hair after only one the exception of those with renal insuffi- to the skin via sweat, concentrating in the week of therapy, with higher concentrations ciency, dose adjustment is not required in stratum corneum. It is quickly cleared from found with longer pulses. Itraconazole can the elderly. skin and hair after cessation of therapy. persist for up to nine months after cessation Terbinafine is generally a very safe Although well tolerated, side effects are of therapy. agent. The most common adverse effects common with the use of griseofulvin and are headache, gastrointestinal symptoms include headaches, photosensitivity, drug Fluconazole and drug eruptions; hepatic and haema- rashes, gastrointestinal disturbance, uri- Fluconazole is a commonly used tological complications are quite uncom- nary and menstrual disturbances, liver broad-spectrum triazole that, like other mon. Blood counts and liver function tests dysfunction and neurological effects azoles, inhibits 14α-demethylase. However, should be performed if terbinafine is to be (fatigue, mood changes, dizziness, blurred it is much less lipophilic and much less used continuously for more than six weeks. vision). Changes to spermatogenesis occur, protein-bound than other azoles. It has One peculiar side effect is a disturbance, and men taking griseofulvin should not very high bioavailability and its absorption or even loss, of taste in some patients, father children for at least six months after is not affected by food. which can be irreversible.Copyright _Layout 1 17/01/12ceasing 1:43 treatment.PM Page 4 When used as a once-a-week 150 mg Terbinafine has no serious drug The use of antacids and H2-antagonists pulse, fluconazole is present in the skin 36 MedicineToday x JUNE 2014, VOLUME 15, NUMBER 6 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2014. TABLE. TREATMENT OPTIONS FOR COMMON CUTANEOUS FUNGAL INFECTIONS Fungal infection First-line therapy Second-line therapy General notes Tinea corporis, Topical terbinafine Oral terbinafine 250 mg for 2 to 4 Keep skin dry Tinea capitis, Topical imidazoles weeks Identify and eliminate Tinea cruris, Fluconazole 200 mg weekly for 2 to source Tinea faciei, 4 weeks (off-label use) Tinea manuum Itraconazole 200 mg twice daily for 1 week per month for several months Griseofulvin 500 mg daily for several