Clotrimazole

Abstract

We describe the incidental clearance of preexisting tinea versicolor skin infection with the treatment of oral isotretinoin therapy for acne vulgaris.

Case Report

A 14-year-old Middle Eastern male presented to our clinic in May 2004 for the treatment of acne vulgaris recalcitrant to oral antibiotic therapy (Monodox[R]). On physical examination, in addition to his moderate inflammatory, papular acne vulgaris, the patient's upper back and shoulders showed the presence of several ill-defined, annular lesions with fine scale and decreased pigmentation. Potassium hydroxide prep was positive for hyphae that were representative of Malassezia furfur. A diagnosis of tinea versicolor (TV) was made. Per patient report, these lesions had been present intermittently for several years. He had moderate treatment success with over-the-counter 1% Ketoconazole shampoo; however, symptoms returned with discontinuation. He was not using any topical therapies for his truncal rash at the time of his clinic visit.

The patient was started on isotretinoin 40 mg twice a day for his acne. At one month follow-up, improvement of the patient's acne vulgaris was noted and his upper back/shoulder lesions had resolved completely. Potassium hydroxide prep at this time was negative for hyphae. The patient completed 5 months of isotretinoin therapy with resolution of his acne vulgaris, and his TV remained clinically clear. Per patient report, his trunk remains clear 9 months after completing his therapy.

Background

TV, also known as pityriasis versicolor, is a common superficial fungal infection of the skin characterized by scaling and pigmentary changes. Lesions associated with this condition are round or oval and range from hyperpigmented or hypopigmented macules and/or patches, (1) measuring 1 to 3 cm in diameter. (2) Lesions follow the pattern of sebaceous gland distribution (3) and appear most commonly on the upper trunk, upper arms, neck, and face. (2) Mild pruritus is occasionally noted, but the condition is generally asymptomatic with cosmetic appearance of color alteration being the primary concern. (2)

Malassezia furfur, a dimorphic lipophilic fungus, has been implicated in the pathogenesis of the disease. Pityrosporum ovale and Pityrosporum orbiculare are other names developed based on micromorphology and the phase of the life cycle in which the organism resides. (1,4) The organism is part of the skin's normal flora. (5) It is found in the stratum corneum and hair follicles, (6) which are rich in sebum. The sebum provides the fungus free fatty acids and triglycerides for nourishment, therefore satisfying the complex lipid requirements for its growth. (1) Early studies have shown the organism growing in a yeast and mycelial phase. In healthy skin, the yeast phase is predominant. The fungus converts from a yeast to a pathogenic mycelial form resulting in mild inflammation due to certain factors including heat, moisture (ie, hyperhidrosis), and occlusion by clothing or cosmetics. (7) Traditional therapy for TV includes topical agents such as selenium sulphide, ciclopirox olamine, and the topical azoles such as clotrimazole and fluconazole. Oral therapies include ketoconazole, itraconazole, and fluconazole. (8)

Isotretinoin (Accutane[R]) is a synthetic derivative of vitamin A which is traditionally used in the treatment of severe, recalcitrant nodular acne and moderately severe acne as well as gram-negative folliculitis, hidradenitis suppurativa, and severe rosacea as well as many other off-label uses. The mechanism of action is not completely understood. However, studies have shown isotretinoin to decrease several quantifiable factors including the size of inflammatory and non-inflammatory lesions, sebaceous gland size, sebum production, the degree of follicular keratinization, and the colony counts of Propionibacteria acnes. (9)

Sebum production is altered by circulating levels of adrogens. (10) Isotretinoin has been shown to decrease skin androgen receptor levels (11) and induce a significant decrease in skin 5[alpha] reduction. (12) Thus, isotretinoin therapy may both directly and indirectly decrease sebum production.

Recent reports indicate effectiveness in treating Pityrosporum folliculitis and seborrhoeic dermatitis with oral isotretinoin therapy. Both articles attribute treatment success to the reduction in sebum secretion or alteration in its biochemical content. (13,14)

While we do not recommend oral isotretinoin for the routine treatment of TV, our observation of clearance during treatment for acne vulgaris leads to a better understanding of the life cycle of M. furfur and the likely requirement for excessive sebum production to yield the pathology behind TV. Such understanding may allow for the development of new, novel topical therapies to help treat this endemic and recurrent condition. Also, concomitant TV with acne requiring isotretinoin treatment does not require additional medication, such as oral ketoconazole or topical antifungals.

References

1. Michalowski R, Rodziewicz H. Pityriasis versicolor in children. Br J Dermatol. 1963;75:397-400.

2. Cohen, Bernard, Mallory. In: Zetelli BJ, Davis HW, eds. Atlas of Pediatric Physical Diagnosis. 3rd ed, St Louis: Mosby Inc; 1997:228.

3. Leeming JP, Norman FH, Holland KT. The distribution and ecology of Malassezia furfur and cutaneous bacteria on human skin. J Appl Bacteriol. 1989;67:47-52.

4. Gordaon MA. Lipophilic yeastlike organisms associated with tinea versicolor. J Invest Dermatol. 1951;17:262-267.

5. Schmidt A. Malessezia furfur: a fungus belonging to the physiological skin flora and its relevance in skin disorders. Cutis. 1997;59:21-29.

6. Mark R, Drawber RPR. In situ microbiology of the stratum corneum. Arch Derm. 1972;105:216-221.

7. Faergemann J. Lipophilic yeasts in skin disease. Semin Dermatol. 1985;4:173-184.

8. Gupta AK, Bluhm R, Summerbell R. Pityriasis versicolor. J Eur Acad Dermatol Venereol. 2002;16:19-33.

9. Orfanos CE, Zouboulis CC, Almond-Roesler B, et al. Current use and future potential role of retinoids in dermatology. Drugs. 1997;53(3):358-388.

10. Strauss JS, Kligman AM, Pochi PE. The effect of androgens and estrogens on human sebaceous glands. J Invest Dermatol. 1962;39:139-55.

11. Boudou P, Soliman H, Chivot M, Villette JM, Vexiau P, Belanger A. Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients. J Clin Endocrinol Metab. 1995;80(4):1158-61.

12. Boudou P, Chivot M, Vexiau P, et al. Evidence for decreased androgen 5a-reduction in skin and liver of men with severe acne after 13-cis-retinoic acid treatment. J Clin Endocrinol Metab. 1994;78:1064-1069.

13. Friedman, SJ. Pityrosporum folliculitis: treatment with isotretinoin. J Amer Acad Dermatol. 1987;16:632-3.

14. Cowley NC, Farr PM, Shuster S. The permissive effect of sebum in seborrhoeic dermatitis: an explanation of the rash in neurological disorders. Br J Dermatol. 1990;122 (1):71-6.

Address for Correspondence

Asra Ali MD

University of Texas

Health Science Center at Houston

Department of Dermatology

6655 Travis Street, Suite 980

Houston, TX 77030

Phone: 713-500-8329

e-mail: Asra.Ali@uth.tmc.edu

Holly Bartell, Brian L Ransdell, MD, Asra Ali MD

University of Texas, Health Science Center at Houston, Department of Dermatology, Houston, TX

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