Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Aditya K. Gupta, Elizabeth A. Cooper and Fiona C. Simpson
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Pityriasis (tinea) versicolor (PV) has a worldwide distribution, though the prevalence is higher in tropical climates than in temperate ones (30–40% vs 1–4%, respectively). PV is caused by the lipophilic yeast species Malassezia. Malassezia organisms are a normal part of human commensal skin flora, and PV results when they are converted from the yeast phase to a mycelial phase which is able to infect the stratum corneum, producing the characteristic hypo- or hyperpigmented lesions.
Infection is associated with sebaceous gland activity, hence infection is most often seen in adults and post-pubescent adolescents, rarely in prepubescent children. An equal prevalence between the sexes has been noted. Predisposing factors include high temperature and humidity, malnutrition, the use of oral contraceptives, hyperhidrosis, genetic susceptibility, increased plasma cortisol levels, and immunodeficiency.
Initially only two species under the genus name Pityrosporum were described. Genetic research in the 1990s confirmed at least seven species of Malassezia, and more have since been discovered. The most common species contributing to PV lesions are M. globosa (50–60%), M. sympodialis (3–59%), M. furfur, and M. slooffiae (each 1–10%). It is not currently known whether the clinical pattern of infection or antifungal susceptibility vary between the different infecting species.
Topical treatment is the first-line therapy in most cases. Topical azoles formulated as gels, creams, solutions, or shampoos (ketoconazole, fluconazole, bifonazole, clotrimazole, miconazole, etc.) have demonstrated efficacy for PV. The allylamine terbinafine has several topical formulations (solution, cream, gel, or spray) that have been used effectively, as have formulations of the benzylamine butenafine. Topical ciclopirox provides both antifungal and anti-inflammatory activity against Malassezia.
Systemic antifungal therapies may be warranted in severe cases, or cases with widespread body involvement, patients with recurrent disease, or those who are immunocompromised. Patients may also prefer a short-duration oral therapy to frequent application of a topical agent.
Second-line therapy for cases refractive to topical therapy may be treated with oral antifungals. Ketoconazole, itraconazole, and fluconazole show high efficacy in the literature. However, in contrast to topical terbinafine, oral terbinafine is not effective, and nor is griseofulvin.
Treatment does not vary with hyperpigmented versus hypopigmented disease. Although fungal organisms may be eradicated after 2 to 4 weeks of therapy, it may take significantly longer before the skin’s normal pigmentation is restored, particularly with hypopigmented lesions.
Relapse of PV is common owing to endogenous host factors: recurrence rates have been reported as high as 60–90% 2 years after treatment. Both ketoconazole (a single 400 mg dose or 200 mg daily for 3 days once monthly) and itraconazole (a single 400 mg dose once monthly for 6 months) have been used in prophylactic regimens for PV, though ketoconazole is not used because of its potential for hepatotoxicity.
Direct microscopy on KOH specimens
Wood’s light
Malassezia organisms should be identified by skin scrapings for definitive diagnosis, and are easily identified where microscopic examination of skin scrapings reveals fungal hyphae in a typical ‘spaghetti and meatball’ pattern. PV lesions fluoresce yellow/green or gold under Wood’s light; however, the examination is positive in only one-third of all PV cases, most likely when the causative organism is M. furfur.
Gupta AK, Kogan N, Batra R. Exp Opin Pharmacother 2005; 6: 165–78.
This is a thorough summary of peer-reviewed studies of topical and oral therapies in the treatment of tinea versicolor until 2005. Azole topical agents have shown good mycological cure, clinical cure, and complete cure in many double-blind randomized clinical trials, as have the non-specific topical agents (zinc pyrithione shampoo, selenium sulfide, etc.) and terbinafine.
Rigopoulos D, Gregoriou S, Kontochristopoulos G, Ifantides A, Katsambas A. Mycoses 2007; 50: 193–5.
Randomized double-blind assignment to either flutrimazole or ketoconazole shampoo, applied to head and body, left on for five minutes before rinsing; application repeated daily for 14 days. No significant difference was found in clinical response between treatments at day 28 (flutrimazole: 86.25%; ketoconazole: 88.5%) or clinical/mycological cure (flutrimazole: 75.9%; ketoconazole: 80.8%).
Montero-Gei F, Robles ME, Suchil P. Int J Dermatol 1999; 38: 601–3.
A randomized open-label trial of a single dose of fluconazole 450 mg, two 300 mg doses of fluconazole given 1 week apart, and itraconazole 200 mg daily for 7 days. Mycological cure rates seen at day 30 were 70%, 97%, and 80%, respectively (a significant difference between the two fluconazole doses), dropping to 55%, 77%, and 78% at day 60. Clinical cure rates at day 60 were 52%, 70%, and 74%, respectively.
Kose O, Bulent Tastan H, Riza Gur A, Kurumlu Z. J Dermatol Treat 2002; 13: 77–9.
A randomized open-label trial compared a single dose of itraconazole 400 mg to itraconazole 200 mg daily for 7 days. Mycological cure rates at week 6 for both regimens were greater than 80%, and clinical cure was 70–80% for the two regimens. There was no significant difference between regimens in outcomes
Farschian M, Yaghoobi R, Samadi K. J Dermatol Treat 2002; 13: 73–6.
A randomized, double-blind clinical trial of fluconazole 300 mg once weekly for 2 weeks versus 400 mg ketoconazole once weekly for 2 weeks (at least 25% of trunk affected). Mycological cure rates for fluconazole and ketoconazole at week 8 were 90% and 88%, respectively, reducing to 82% and 78%, respectively, at week 12.
Faergemann J, Gupta AK, Al Mofadi A, Abanami A, Shareaah AA, Marynissen G. Arch Dermatol 2002; 138: 69–73.
Patients achieving mycological cure after open treatment with itraconazole 200 mg once daily for 7 days entered a double-blind, placebo-controlled trial of itraconazole prophylaxis (itraconazole or placebo: 200 mg twice daily 1 day per month for 6 consecutive months). At the end of prophylaxis, 88% of itraconazole patients remained mycologically negative, compared to only 57% of placebo-treated patients (p < 0.001).
Partap R, Kaur I, Chakrabarti A, Kumar B. Dermatology 2004; 208: 55–9.
A randomized trial of patients with 15% or more skin surface area involvement, compared single doses of fluconazole (400 mg) and itraconazole (400 mg). At week 8, fluconazole showed a greater proportion of patients with reduced scaling and no residual pigmentation compared to itraconazole (65% and 20% vs 35% and 5%, respectively), though the difference did not reach statistical significance. Mycological cure for fluconazole was also higher than for itraconazole (65% vs 20%). Relapse was seen in both groups (fluconazole 35%, itraconazole 60%).
Yazdanpanah MJ, Azizi H, Suizi B. Mycoses 2007; 50: 311–13.
A randomized trial compared single-dose ketoconazole 400 mg to a fluconazole 300 mg dose once weekly for 2 weeks in patients with >25% body area affected. Clinical improvement rates 30 days after the start of treatment in the two groups were 87.9% and 81.5%, respectively (p = 0.37).
Dehghan M, Akbari N, Alborzi N, Sadani S, Keshtkar AA. J Dermatol 2010; 37: 699–702.
Patients were randomized to receive a single 400 mg dose of oral fluconazole with placebo cream to be applied twice daily for 2 weeks or a placebo capsule with 1% clotrimazole cream to be applied twice daily for 2 weeks. At the end of the 12-week follow-up period, 92% of the fluconazole group achieved complete cure whereas 81.8% of the clotrimazole group achieved complete cure (p = 0.77).
Faergemann J, Todd G, Pather S, Vawda ZFA, Gillies JD, Walford T, et al. J Am Acad Dermatol 2009; 61: 971–6.
Participants were randomized into six pramiconazole treatment groups: (1) 100 mg taken once; (2) 200 mg taken once; (3) 200 mg taken once daily for 2 days; (4) 200 mg taken once daily for 3 days; (5) 400 mg taken once; (6) placebo taken once daily for 3 days. The primary efficacy outcome was effective treatment (negative KOH microscopy and resolution of erythema, desquamation, and pruritus or minimal residuals for participants with severe baseline scores). At day 28, the highest proportion of participants with an effective cure received 200 mg daily for 2 days, 84.0% (95% CI: 69.6 to 98.4) and 200 mg daily for 3 days, 84.6% (95% CI: 70.7 to 98.5).
Pramiconazole is not currently approved or marketed. As more data accumulates, the level of evidence may alter.
Shi T, Ren X, Yu H, Tang Y. Dermatol 2012; 224: 184–8.
A prospective, randomized, double-blind clinical trial compared adapalene cream and 2% ketoconazole cream applied to the torso twice daily for 2 weeks. No significant difference was found in clinical response and mycological cure for ITT or per protocol analysis between treatments at 4 weeks. Participants experienced 75% and 70% mycological cure in the adapalene and ketoconazole groups, respectively.
Adapalene is not an antifungal drug; results are based on alterations in the skin’s properties.
Gold MH, Bridges T, Avakian E, Plaum S, Pappert EJ, Fleischer AB, et al. Skinmed 2011; 9: 283–6.
Participants received 1% naftifine gel twice daily for two weeks. At 6 weeks post-treatment, 50% of the participants had achieved a mycological cure.
Bartell H, Ransdell BL, Ali A. J Drugs Dermatol 2006; 5: 74–5.
This is a single case report of a 14-year-old boy presenting with acne vulgaris recalcitrant to oral antibiotic therapy, who also presented with PV infection on the upper back and shoulders. One month after starting oral isotretinoin 40 mg twice daily, the PV lesions had completely resolved. Resolution was attributed to the sebum-altering properties of isotretinoin.
The use of isotretinoin cannot be advocated because of the potential for serious side effects, particularly in females. In cases of concomitant PV and acne, no additional medication may be required for the PV infection.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Ketoconazole
Bifonazole
Terbinafine
Clotrimazole
Econazole
Oxiconazole
Butenafine
Ciclopirox
Fluconazole shampoo
Selenium sulfide 2.5%
Tioconazole
Zinc pyrithione shampoo
Itraconazole
Ketoconazole
Fluconazole
Itraconazole
Pramiconazole (oral triazole)
Adapalene
Naftifine (topical allylamine)
Isotretinoin
