Med. Mycol. J. Vol.Med. 57E, Mycol. E 63 J. − Vol. E 66, 57（No. 2016 3）, 2016 E63 ISSN 2185 − 6486

Short Report Treatment Outcomes for in the Dermatology Department of a University Hospital in Japan

Chikako Suzuki, Midori Hase, Harunari Shimoyama and Yoshihiro Sei

Department of Dermatology, Teikyo University Hospital

ABSTRACT

Topical or systemic antifungal therapy was administered to patients diagnosed with Malassezia folliculitis during the 5-year period between March 2007 and October 2013.The diagnosis of Malassezia folliculitis was established on the basis of characteristic clinical features and direct microscopic findings（10 or more -like fungi per follicle）.Treatment consisted of topical application of 2% ketoconazole cream or 100 mg oral itraconazole based on symptom severity and patientsʼ preferences. Treatment was given until papules flattened, and flat papules were examined to determine whether the patientʼs clinical condition had “improved” and the treatment had been “effective”.The subjects were 44 patients（35 men, 9 women）, with a mean disease period of 25 ± 15 days.In regard to the lesion site, the frontal portion of the chest was the most common, accounting for 60% of all patients.The mean period required for improvement was 27 ± 16 days in 37 patients receiving the topical antifungal agent and 14 ± 4 days in the 7 patients receiving the systemic antifungal agent.The results were “improved” and the treatment was “effective” in all patients.Neither treatment resulted in any adverse reactions.Although administration of oral agents has been recommended for the treatment of Malassezia folliculitis, this study revealed that beneficial results are safely obtained with topical antifungal therapy alone, similar to those of systemic antifungal agents. Key words：Malassezia folliculitis, diagnosis, treatment, ketoconazole cream, itraconazole

and ultraviolet exposure3）. Introduction Malassezia folliculitis eruptions are commonly distributed over the neck, chest, back, and the In 1968, Graham forwarded a disease concept extensor side of the upper arm.They also occur designated as Pityrosporum folliculitis1）.Furth- on the face in rare instances.They are dome- ermore, Potter et al.emphasized in 1973 that this shaped erythematous papules or pustules 2-3 mm disease is not rare, although it easily goes in size.Although they are on occasion confused unrecognized and is not uncommonly misdi- with , there are few comedos, and they are agnosed as acne, folliculitis, or eczema 2）. characteristically accompanied by mild pruritus. The genus Malassezia includes lipophilic The disease is diagnosed in patients with charac- present in the follicle infundibulum, with teristic clinical features and clusters containing counts and species varying among sites.These multiple yeasts（≥10 per visual field at 400 × yeasts undergo transition from the yeast to the magnification）under direct microscopic exami- mycelial form under certain conditions. Malasse- nation4）. zia folliculitis occurs when Malassezia grows in Although the results of topical or systemic yeast form in follicles under conditions such as antifungal treatment have been reported 5）, there high temperature and humidity, excessive sweat- are persisting issues, such as adverse reactions ing, being covered with clothes, cosmetics, or oil, associated with these drugs and the appearance

Address for correspondence : Chikako Suzuki Department of Dermatology, Teikyo University Hospital, Mizonokuchi, 3-8-3, Mizonokuchi, Takatu, Kanagawa 213-0001, Japan Received : 3, February 2016, Accepted: 23, March 2016 E-mail : [email protected] E64 Medical Mycology Journal Volume 57, Number 3, 2016 of drug-resistant yeasts6）.Thus, there are as yet sensation.The most common time of onset was no internationally approved guidelines for its summer（April to August）, reported by 75% of all treatment 7）. patients.Nine patients（20.5%）hadan underlying Malassezia folliculitis is a common and well- disease, eight（18.2%）had a history of topical known disease, although the number of reports is steroid treatment for underlying diseases such as surprisingly low.We summarize herein the treat- atopic dermatitis, and one was receiving oral ment results of patients with Malassezia folliculitis steroids for adult Stillʼs disease. diagnosed in our department. For treatment, 37 patients received topical application of 2% KCZ cream, and the mean time Subjects and Methods required for improvement was 27 ± 16 days（9-56 days）.Seven patients were given oral ITCZ 100 We retrospectively analyzed the medical re- mg; the mean time required for rash improvement cords of 44 patients receiving a diagnosis of was 14 ± 4 days（9-21 days）. Malassezia folliculitis during the 5-year period Since the papules disappeared or flattened in all between March 2007 and October 2013. patients, they were considered to have “im- For diagnosis, a pus specimen was squeezed proved” and “responded to treatment.” Fig. 1, 2 out and collected from a papule or a pustule using show the courses of three patients who received ophthalmic tweezers in patients suspected of treatment.Fig.3 presents direct microscopic having Malassezia folliculitis, and it was then images.During the treatment period, no adverse stained with acidic methylene blue. Malassezia reactions clearly associated with the medications folliculitis was diagnosed when 10 or more yeast were noted in any of the patients receiving a organisms per follicle were observed under direct topical or systemic antifungal agent. microscopic examination. Topical or systemic antifungal treatment was Discussion chosen based on the symptom severity（area of the lesion and the number of eruptions）and the The genus Malassezia includes fungi most patientʼ s own preferences, and the use or non- commonly present on the skin surface8）.In order use of drugs contraindicated for concomitant to accurately diagnose Malassezia folliculitis, it is administration with itraconazole（ITCZ）.This in- important to proactively perform direct microsco- formation was collected through a detailed inter- pic examination in patients suspected to have this view process.The two drugs were not used disease.Since Malassezia is present in the hair concurrently in any of our subjects.As topical follicle infundibulum, it is critical to sufficiently antifungal treatment, patients received simple collect the contents of the papule or pustule application of 2% ketoconazole（KCZ）cream containing sebum at the time of microscopic twice daily.As systemic antifungal treatment, examination.After appropriate staining, numer- patients orally took ITCZ 100 mg once daily. ous Malassezia yeasts are often observed at oil- Treatment was given until papules flattened, and rich sites. patients with flat papules were considered to Malassezia folliculitis, which is occasionally have “improved” and the treatment to have been encountered in daily medical practice, is rarely “effective”.Pictures were taken of the lesions diagnosed correctly.Thus, the actual situation of before and after the treatment. this disease has not been adequately elucidated. It is usually misdiagnosed as intractable acne or Results eczema in many patients, resulting in inappropri- ate treatment.Among approximately 350 patients There were 44 patients（35 men, 9 women）with with acneiform eruptions, the 44 described herein a mean age of 36 ± 12 years（range, 15-60 years）. were Malassezia yeast-positive, yielding a correct The mean disease period was 25 ± 15 days（9-56 diagnosis of Malassezia folliculitis. days）.The lesions were located in the frontal Malassezia folliculitis was formerly treated portion of the chest in 60% of the patients（chest, primarily with oral antifungal agents 5）.However, 60%; neck, 10%; back, 20%; extensor side of the many issues related to this treatment have been upper arm, 5%; others, 5%）.Approximately 80% of reported, including the onset of adverse reac- all patients had complained of a mild itching tions, the appearance of drug-resistant bacteria, Med. Mycol. J. Vol. 57（No. 3）, 2016 E65

（ａ） （ｂ） Fig.1．a: Twenty days after oral administration of prednisolone for adult Still's disease, a 26-year- old man presented with numerous red papules and pustules, the size of half a grain of rice, and corresponding to follicles all over the frontal portion of the chest.He had mild associated pruritus. b: Eighteen days after topical therapy with KTCZ.Although he was still taking oral prednisolone at 25 mg, his papules showed a flattening trend.The papules had mostly disappeared 28 days after topical therapy, and the patient was thus considered to have “improved”.

Fig.2．a: A 31-year-old woman presented with numerous red papules, the size of half a grain of rice, and corresponding to follicles on the extensor side of the upper arm.She had atopic dermatitis as an underlying disease.She visited our hospital as there was no improvement with treatment for eczema at another clinic. b: Twenty days after topical therapy with KCZ. Since the papules had mostly disappeared, she was considered to have “improved”. （ａ） （ｂ）

and minimal efficacy 6）.There are no interna- tionally approved guidelines for treating Malasse- zia folliculitis at present.In 2015, Hald et al. summarized Malassezia-related skin diseases and reported that systemic antifungal treatment is probably more effective than topical therapy, but recommended that the two be combined 7）.As to approaches other than systemic and topical antifungal treatments, Lee et al.reported photo- dynamic therapy for treatment-resistant Malasse- zia folliculitis, but their study had a small sample size and further research is needed in this area6）. Fig.3．Direct microscopic examination (acidic In this study, clinical symptoms improved within methylene blue staining; scale bar, 50 μm).Multiple yeasts with unipolar budding and stained violet one month in all patients that received the topical can be seen in a cluster. antifungal agent solely.Although it requires E66 Medical Mycology Journal Volume 57, Number 3, 2016 longer time for improvement by topical treatment 55: 1772-1774, 2013. in comparison with systemic therapy, topical 4）Yoshihiro Sei: Malassezia infection.Med.Mycol.J antifungal therapy is a safe and beneficial treat- 53: 77-11, 2012. 5）Abdel-Razek M, Fadaly G, Abdel-Raheim M, Al- ment for Malassezia folliculitis. Morsy F: Pityrosporum（malassezia）folliculitis in Saudi Arabia: diagnosis and the therapeutic trials. Conflict of Interest Clin Exp Dermatol 20: 406-409, 1995. 6）Lee JW, Kim BJ, Kim MN: Photodynamic therapy: All authors declare no conflict of interest. new treatment for recalcitrant Malasezzia folliculi- tis.Lasers Surg Med 42: 192-196, 2010. 7）Hald M, Arendrup MC, Svejgaaed E, Lindskov R, References Foged EK, Ditte Marie, Saunte DML: Evidence- based Danish guidelines for the treatment of 1）Graham JH: Pityrosporum ovale in the discussion. Malassezia-related skin diseases.Acta Derm Arch Dermatol 98: 421, 1968. Venereol 95: 12-19, 2015. 2）Potter BS, Burgoon CF JR, Johnson WC: Pityros- 8）Findley K, Oh J, Yang J, Conlan S, Deming C, porum folliculitis: report of seven cases and Meyer JA, Schoenfeld D, Nomicos E, Park M: review of the Pityrosporum organism relative to Topographic diversity of fungal and bacterial cutaneous disease.Arch Dermatol 107: 388-391, communities in .Nature 498: 367-370, 1973. 2013. 3）Yoshihiro Sei: Malassezia folliculitis.Hihu Rinsho