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Efficacy and Safety of C/P Cream for Facial SD

pISSN 1013-9087eISSN 2005-3894


Ann Dermatol Vol. 28, No. 6, 2016 https://doi.org/10.5021/ad.2016.28.6.733

ORIGINAL ARTICLE

Efficacy and Safety of Cream Containing


Climbazole/Piroctone Olamine for Facial Seborrheic
Dermatitis: A Single-Center, Open-Label Split-Face
Clinical Study
Hae Jeong Youn1, Soo Young Kim1, Minji Park2, Won Hee Jung2, Yang Won Lee1,3,
Yong Beom Choe1,3, Kyu Joong Ahn1,3
1
Department of Dermatology, Konkuk University School of Medicine, Seoul, 2Department of Systems Biotechnology, Chung-Ang
University, Anseong, 3Research Institute of Medical Science, Konkuk University, Seoul, Korea

Background: Seborrheic dermatitis (SD) is a multifactorial lient cream-treated left side. For the C/P cream, the MICs
disease; Malassezia species play an important role in its were 0.625, 5, 0.625, and 2.5 mg/ml for Malassezia restricta,
pathogenesis. Objective: We aimed to determine whether a M. globosa, M. sympodialis, and M. slooffiae, respectively.
cream containing climbazole/piroctone olamine (C/P Conclusion: Based on the reduced casual sebum level and
cream), antifungal agents with expected efficacy against extent of erythema, the antifungal activity of C/P cream
Malassezia species, could improve SD symptoms. Methods: against Malassezia species seems useful for the treatment of
We instructed 24 patients with mild-to-moderate SD to apply mild to moderate SD. (Ann Dermatol 28(6) 733739, 2016)
the C/P cream and emollient cream on the right and left sides
of the face, respectively, every morning and evening for 4 -Keywords-
weeks. The casual sebum level (measured with Sebumeter; Climbazole, Malassezia species, Piroctone olamine,
Courage & Khazaka Electronic GmbH, Germany) and the ex- Seborrheic dermatitis

tent of erythema (measured with Mexameter ; Courage &
Khazaka Electronic GmbH) on the face were measured at
baseline and after 4 weeks. The minimal inhibitory concen- INTRODUCTION
tration (MIC) was determined to demonstrate the antifungal
activity of the C/P cream. Results: The casual sebum level and Seborrheic dermatitis (SD) is a chronic dermatitis that af-
1
erythema were measured at week 4, and the median values fects 1%3% of the population . SD is characterised by
demonstrated a quantitative improvement on the C/P sharply defined erythematous patches and plaques with
cream-treated right side of the face compared to the emol- greasy-looking, yellowish scales on seborrheic areas such
as the scalp, face, upper trunk, and flexures. The growth of
Received November 13, 2015, Revised April 8, 2016, Accepted for Malassezia species was suggested as an important patho-
publication April 11, 2016 genic factor of SD2,3, as demonstrated by studies that
Corresponding author: Yang Won Lee, Department of Dermatology, Konkuk showed that SD was improved by the use of antifungal
University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul
agents4,5. Current treatment options include antifungal
05030, Korea. Tel: 82-2-2030-5172, Fax: 82-2-2030-5179, E-mail: 20050078@
kuh.ac.kr drugs, anti-inflammatory agents (steroids, calcineurin in-
This is an Open Access article distributed under the terms of the Creative hibitors, and lithium salts), keratolytic agents, and photo-
Commons Attribution Non-Commercial License (http://creativecommons. therapy. SD is usually treated with topical corticosteroids
org/licenses/by-nc/4.0) which permits unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work
and antifungals. However, prolonged use of topical ste-
is properly cited. roids may cause adverse effects such as skin atrophy, te-
Copyright The Korean Dermatological Association and The Korean langiectasia, rosacea, and acne. The use of topical anti-
Society for Investigative Dermatology fungal agents in the treatment of mild SD is well

Vol. 28, No. 6, 2016 733


HJ Youn, et al

established. Itraconazole can be prescribed for moderate to DS+), which contains climbazole and piroctone ol-
severe facial SD and result in significant clinical improve- amine, on the right side of the face and emollient cream
ment and decrease in the growth of Malassezia species6. (Atoderm; Bioderma Laboratoire Dermatologique), a
The cream containing climbazole/piroctone olamine (C/P moisturizer that does not contain climbazole and pir-
cream) (Sensibio DS+; Bioderma Laboratoire Dermatol- octone olamine, on the left side every morning and eve-
ogique, Lyon, France) tested in this study is a cosmetic ning for 4 weeks. The use of other cosmetics, therapeutic
product containing piroctone olamine and climbazole. external preparations, and drugs that could affect the clin-
Piroctone olamine, the ethanolamine salt of the hydroxa- ical trial was prohibited during the study. At the baseline
mic acid derivative piroctone, is a hydroxypyridone an- visit and at 4 weeks, (1) Sebumeter and Mexameter
ti-mycotic agent. Climbazole is an imidazole antifungal (Courage & Khazaka Electronic GmbH, Cologne, Germany)
agent. A non-steroidal cream containing piroctone olamine were used to measure the casual sebum level and most in-
was reported to effectively treat SD by inhibiting the tense erythema on the forehead and cheek on both sides;
growth of Malassezia species7, and a shampoo containing and (2) patients were asked to subjectively score their itch-
piroctone olamine and climbazole effectively reduced iness, burning sensation, erythema, scaling, and tightness
dandruff by suppressing the growth of Malassezia8. on each side of the face as none, 0; mild, 1; moderate, 2;
However, no study thus far has reported on an over- or severe, 3. This research was conducted in winter from
the-counter product containing piroctone olamine and November to December.
climbazole for the treatment of facial SD. We aimed to
Safety evaluation
evaluate the efficacy and safety of C/P cream in the treat-
ment of facial SD. Safety was assessed by inquiring about local irritation or
other adverse events by using questionnaires.
MATERIALS AND METHODS Antifungal assay
Patients
To determine the antifungal activity of the C/P cream and
This 4-week single-center, open-label split-face study was emollient cream against specific Malassezia species
approved by the institutional review board of Konkuk strains, their minimal inhibitory concentrations (MICs)
University Medical Center (IRB no. KUH1120054). All of were measured in a laboratory. MIC is the lowest concen-
the patients included in this study signed an informed con- tration of antifungals or antibiotics that will inhibit the visi-
sent form. The participants were 24 patients diagnosed ble growth of a microorganism after overnight incubation.
with facial symmetric mild-to-moderate SD by a dermato- Malassezia restricta, M. sympodialis, and M. slooffiae
logist. The severity of SD9 was determined by using two were isolated and identified at Konkuk University Medical
scales; one scored erythema, plaque, infiltration, and pus- Center, South Korea, and M. globosa (Centraalbureau voor
tules as absent (0), mild (1), moderate (2), or severe (3), Schimmelcultures [CBS] 7966) was purchased from the
and the other scored the extent of lesions as less than 10% CBS Fungal Biodiversity Center. These strains were grown
(1), 10%30% (2), 30%50% (3), 50%70% (4), or on Leeming and Notman agar medium10 (0.5% glucose,
more than 70% (5). The total score was calculated by mul- 1% polypeptone, 0.01% yeast extract, 0.8% bile salt,
tiplying the severity by the lesion area of erythema, plaque, 0.1% glycerol, 0.05% glycerol monostearate, 0.05%
infiltration, and pustules, respectively, and adding the tween 60, 1.2% agar, 0.5% whole fat cow milk, and 170
scores of all four items. The total scores were categorised g/ml chloramphenicol). Susceptibility testing of the C/P
into mild (5 points), moderate (611), or severe (12 cream and emollient cream was performed according to a
60). Patients who used any oral drug that could affect the method described previously11. Antifungal assays were re-
condition of the skin (steroids, antibiotics, antifungal peated twice, and identical results were obtained.
agents, antihistamines, etc.) within 4 weeks of study entry
Statistical analysis
or any therapeutic external preparation within 2 weeks of
study entry were excluded. Patients with a skin disease The Wilcoxon signed rank test was used to compare the
other than SD and those who underwent a facial proce- values in the C/P cream-treated area with respective val-
dure within 6 months of study entry were excluded as ues in the emollient-treated area. Significance levels were
well. set at p0.05. Analyses were performed using SPSS ver.
23.0 for Windows (SPSS Inc., Chicago, IL, USA).
Treatment and assessment
The patients were instructed to apply C/P cream (Sensibio

734 Ann Dermatol


Efficacy and Safety of C/P Cream for Facial SD

RESULTS ing Sebumeter and Mexameter , and compared at base-


line and 4 weeks. At week 4, the C/P cream-treated area
Study population
showed a statistically significant reduction in the median
The patients mean age was 35.37 years. We enrolled 24 casual sebum level on the forehead (marked with a black
Korean patients (6 men and 18 women), none of whom bold line in Fig. 1) compared to the emollient cream-treat-
withdrew from the study. ed area (p=0.011). On the cheek, the C/P cream-treated
area also showed a lower median casual sebum level
Efficacy of the C/P cream in comparison with that of
compared to the emollient-treated area, but this was not
the emollient cream
statistically significant (Fig. 1). At week 4, the C/P cream-treat-
ed area showed a statistically significant reduction (p=0.002)
1) Assessment of the changes in the objective SD symptoms
in median erythema level compared to the emollient
The casual sebum level and extent of erythema on the left- cream-treated area, on both the forehead and the cheek
and right-side forehead and cheek were measured by us- (Fig. 2).

2) Evaluation of the changes in the subjective SD symptoms


A questionnaire was administered at baseline and 4 weeks
to determine differences in symptoms between the left

Fig. 1. The casual sebum level measured using Sebumeter and



Mexameter (Courage & Khazaka Electronic GmbH, Germany)
at baseline and week 4. A p-value0.05 was considered
statistically significant (*p0.05). C/P cream: cream containing
climbazole/piroctone olamine.
Fig. 3. Symptom intensity reported by patients at baseline. C/P
cream: cream containing climbazole/piroctone olamine.


Fig. 2. Erythema measured using Sebumeter and Mexameter
(Courage & Khazaka Electronic GmbH, Germany) at baseline and
week 4. A p-value0.05 was considered statistically significant
(*p0.05). C/P cream: cream containing climbazole/piroctone Fig. 4. Symptom intensity reported by patients at week 4. C/P
olamine. cream: cream containing climbazole/piroctone olamine.

Vol. 28, No. 6, 2016 735


HJ Youn, et al

and right sides of the face (Fig. 3, 4). The week 4 median ing inflammatory and hyper-proliferative epidermal re-
15
itchiness, burning sensation, and erythema were reduced sponses . The following are the four sequential pathophy-
in both the C/P cream-treated area and emollient siological phases of SD15: 1) Malassezia ecosystem and in-
cream-treated area, suggesting that the patients subjective teraction with the epidermis; 2) initiation and propagation
symptoms improved with both treatments; there was no of inflammation; 3) disruption of proliferation and differ-
statistically significant difference between the two entiation processes of the epidermis; and 4) physical and
treatments. functional skin barrier disruption. According to these phas-
es, if the proliferation of Malassezia species is controlled,
Adverse events
the progression of the pathophysiological phases of SD
No serious adverse effects requiring medical treatment and its signs and symptoms would be improved.
were reported, although 2 patients reported a temporary Climbazole [(1-4-chlorophenoxy)-1-(1H-imidazonyl)-3,3-
pricking sensation after application of the C/P cream. dimethylbutan-2-one] is an imidazole antifungal agent
commonly used in the treatment of human fungal skin in-
Antifungal activity of the C/P cream and emollient cream
fections such as dandruff and SD. Similarly, with other
The antifungal activity of the C/P cream and emollient azole antifungal agents, climbazole is thought to exhibit
cream against Malassezia species was measured (Table 1). antifungal activity by inhibiting ergosterol, a major com-
The MIC of the C/P cream, an index indicating antifungal ponent of fungal cytoplasmic membranes. Azoles that
agent activity, was 0.625 mg/ml for M. restricta, 5 mg/ml bind to a cytochrome P-450 molecule are involved in the
for M. globosa, 0.625 mg/ml for M. sympodialis, and 2.5 synthesis of ergosterol16. Azoles bind by their basic nitro-
mg/ml for M. slooffiae, indicating antifungal activity gen to the heme iron and by their N-1 substituent to the
against all the aforementioned species. The C/P cream is a protein moiety of fungal P-450s, resulting in the blocking
crude mixture. The concentrations of climbazole and pir- of P-450-mediated reactions17.
octone olamine, which are single compounds with anti- Piroctone olamine [1-hydroxy-4-methyl-6(2,4,4-trimethylpentyl)-
fungal action, were re-evaluated in order to determine 2(1H)-pyridone, 2-aminoethanol salt] is a pyridine derivate,
whether their antifungal activities were proportionate to as is ciclopirox olamine. It is a component of many cosmetic
the amounts of their active ingredients. This substance products such as anti-dandruff shampoo and is known to
was also shown to be effective against M. restricta, M. glo- have a fungicidal effect. Piroctone olamine penetrates the
bosa, M. sympodialis, and M. slooffiae. The emollient cell membrane and forms complexes with iron ions, inhibit-
cream was not observed to exert any antifungal activity. ing energy metabolism in mitochondria18. Piroctone ol-
amine has been approved for use in cosmetic products at a
DISCUSSION maximal concentration of 1% (rinse-off products) or 0.5%
(other products).
The pathophysiological mechanism of SD remains unclear. The C/P cream tested in this study is a topical agent con-
Although Malassezia species are a part of the normal mi- taining both climbazole and piroctone olamine, as well as
croflora found on normal skin of 75% to 98% of healthy other effective ingredients such as 18-glycyrrhetinic acid
adults12, its role in SD has been supported by the positive and golden algae extract (Laminaria ochroleuca). 18-
correlation between the population density of Malassezia glycyrrhetinic acid is extracted from the root of the liq-
13
species on the skin and the severity of SD , as well as the uorice plant, a perennial plant with upright stems covered
high therapeutic efficacy of antifungal agents in SD14. The with leaves and lilac-coloured flowers. It provides imme-
current understanding of the pathophysiological mecha- diate relief owing to its endogenous anti-inflammatory
nism of SD suggests a role of Malassezia species in trigger- properties19. Golden algae extract (L. ochroleuca) is a lipi-

Table 1. Minimal inhibitory concentration measured to determine the antifungal activity of the cream containing climbazole/piroctone
olamine (C/P cream)
Malassezia species C/P cream (mg/ml) Piroctone olamine (g/ml) Climbazole (g/ml) Emollient cream (mg/ml)
M. globosa 0.625 1.25 0.3125 N/A
M. restricta 5 10 2.5 N/A
M. sympodialis 0.625 1.25 0.3125 N/A
M. slooffiae 2.5 5 1.25 N/A
N/A: no antifungal activity detected.

736 Ann Dermatol


Efficacy and Safety of C/P Cream for Facial SD

dic extract of golden algae. It reduces skin reactivity by in- cheeks, and chest of Korean patients with SD31. In a study
hibiting the synthesis of the cytokines involved in the irri- involving Japanese patients with facial SD, M. globose
tation20. (93.5%) and M. restricta (61.3%) were the two most com-
The patients in the present study showed significant im- monly detected Malassezia species by using a PCR-based,
18
provements in SD according to the results of Sebumeter non-culture dependent method . Considering the anti-
and Mexameter. In the patient satisfaction questionnaire, fungal activity of the C/P cream against M. restricta, M.
patients reported an improvement in itchiness, burning globosa, M. sympodialis, and M. slooffiae, the SD symp-
sensation, and erythema in both the C/P cream-treated toms seemed improved by its antifungal activity against
right side of the face and emollient cream-treated left side. Malassezia species especially M. restricta, the most fre-
But because there was no marked difference between the quently occurring species on the face.
right and left sides, it may have been difficult for patients SD shows a strong correlation with sebaceous gland activ-
to sense and describe the symptom improvement ity32. SD is most common in adolescence and young
separately. adulthood, when sebaceous glands are at their most
The advantages of the C/P cream are that it can be pur- active. In addition, the SD lesions were distributed on
chased without prescription, can replace lotion applied parts of the body where sebaceous glands were present,
every day after facial wash, and can mitigate the symp- such as the face, scalp, chest, and back1. SD is considered
2,3
toms of SD without serious adverse effects that require to be a Malassezia driven disease and Malassezia spe-
32
medical treatment. The disadvantage was that the moistu- cies require lipids . We measured the casual sebum level
rising effect was not sufficient to prevent skin tightness in expecting that a reduction in the amount of casual sebum
the winter; the patients often mentioned that they would would be associated with reduced proliferation of
like to use it in the summer. Malassezia species, which would result in an improve-
We determined the MICs for Malassezia species in order ment in the symptoms of SD. Looking at the final results,
to examine the antifungal activity of the C/P cream. The since the symptoms of SD seemed to improve in the C/P
C/P cream is a crude mixture, and simple comparison with cream-treated right facial side which also showed a nota-
single compounds in terms of MIC for Malassezia species ble reduction in its casual sebum level, this suggests that
may not be feasible. To resolve this issue, we re-examined reducing the casual sebum level may assist indirectly in
the concentrations of climbazole and piroctone olamine improving the symptoms of SD.
to determine whether their active ingredients validly re- This study has some limitations. This was a simple, sin-
flected their degree of antifungal activity. Schmidt and gle-center open-label study. The number of patients was
Rhl-Hrster21 found that the MICs of climbazole and ke- small (n=24). The long-term efficacy of the C/P cream
toconazole for M. furfur were 0.06 g/ml. In another tested was not evaluated. Therefore, additional clinical da-
22
study, Schmidt found that the MIC of climbazole for M. ta are required to determine the long-term efficacy and
pachydermatis was 0.06 g/ml. Prabhamanju et al.23 safety of the C/P cream tested.
reported that for M. furfur, the MIC of climbazole was In conclusion, based on the reduction of the casual sebum
20 g/ml and that of piroctone olamine was 5 g/ml. level and the extent of erythema, this C/P cream with anti-
Gokulshankar et al.24 reported that the MICs of climbazole fungal activity against Malassezia species seems useful for
for M. furfur, M. globosa, and M. restricta were 62.5, 125, the treatment of mild-to-moderate SD. The objective im-
and 125 g/ml, respectively. Considering the above-men- provement in SD was associated with anti-Malassezia ac-
tioned findings in the literature, climbazole and piroctone tivity of C/P cream.
olamine in the C/P cream can be expected to have anti-
fungal activities against M. restricta, M. globosa, M. sym- ACKNOWLEDGMENT
podialis, and M. slooffiae.
The use of cultural and phenotypical typing methods re- This work was supported by the Basic Science Research
sulted in contradictory data about the proportion of Program through the National Research Foundation of
Malassezia species in SD25-27. However, the molecular Korea (NRF), funded by the Ministry of Science, ICT, and
analysis of Malassezia species in SD demonstrated that M. Future Planning NRF-2013R1A1A2007863 and Bioderma
restricta was consistently the most common28-30. Accord- Laboratoire Dermatologique.
ing to a study on the distribution of Malassezia species in Bioderma Laboratoire Dermatologique provided the re-
the human body that used 26S rDNA polymerase chain search funding, as well as the Sensibio DS+ and Atoderm
reaction (PCR)-restriction fragment length polymorphism, distributed to the patients free of charge, but had no partic-
M. restricta was detected dominantly in the forehead, ipation in the study proceedings, data analysis, or the proc-

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HJ Youn, et al

ess of manuscript preparation and submission. 16. Van den Bossche H, Willemsens G, Cools W, Cornelissen
F, Lauwers WF, van Cutsem JM. In vitro and in vivo effects
of the antimycotic drug ketoconazole on sterol synthesis.
REFERENCES Antimicrob Agents Chemother 1980;17:922-928.
17. Joly V, Bolard J, Yeni P. In vitro models for studying toxicity
1. Gupta AK, Bluhm R. Seborrheic dermatitis. J Eur Acad of antifungal agents. Antimicrob Agents Chemother 1992;
Dermatol Venereol 2004;18:13-26. 36:1799-1804.
2. Elewski BE. Safe and effective treatment of seborrheic 18. Kim Y, Alpmann P, Blaum-Feder S, Krmer S, Endo T, Lu D,
dermatitis. Cutis 2009;83:333-338. et al. Increased in vivo efficacy of lenalidomide by addition
3. Gupta AK, Bluhm R, Cooper EA, Summerbell RC, Batra R. of piroctone olamine. In Vivo 2011;25:99-103.
Seborrheic dermatitis. Dermatol Clin 2003;21:401-412. 19. Scrivener Y, Cribier B. Pathogenesis of seborrheic
4. Alizadeh N, Monadi Nori H, Golchi J, Eshkevari SS, dermatitis. Ann Dermatol Venereol 2004;131:119-122.
Kazemnejad E, Darjani A. Comparison the efficacy of 20. Tsukahara M, Nishino T, Furuhashi I, Inoue H, Sato T,
fluconazole and terbinafine in patients with moderate to Matsumoto H. Synthesis and inhibitory effect of novel
severe seborrheic dermatitis. Dermatol Res Pract 2014; glycyrrhetinic acid derivatives on IL-1 beta-induced
2014:705402. prostaglandin E(2) production in normal human dermal
5. Kastarinen H, Okokon EO, Verbeek JH. Topical anti- fibroblasts. Chem Pharm Bull (Tokyo) 2005;53:1103-1110.
inflammatory agents for seborrheic dermatitis of the face or 21. Schmidt A, Rhl-Hrster B. In vitro susceptibility of
scalp: summary of a Cochrane Review. JAMA Dermatol Malassezia furfur against azole compounds. Mycoses 1996;
2015;151:221-222. 39:309-312.
6. Shemer A, Kaplan B, Nathansohn N, Grunwald MH, 22. Schmidt A. In vitro activity of climbazole, clotrimazole and
Amichai B, Trau H. Treatment of moderate to severe facial silver-sulphadiazine against isolates of Malassezia pachy-
seborrheic dermatitis with itraconazole: an open non- dermatis. Zentralbl Veterinarmed B 1997;44:193-197.
comparative study. Isr Med Assoc J 2008;10:417-418. 23. Prabhamanju M, Gokul Shankar S, Babu K, Ranjith MS.
7. Del Rosso JQ. Adult seborrheic dermatitis: a status report on Herbal vs. chemical actives as antidandruff ingredients-which
practical topical management. J Clin Aesthet Dermatol are more effective in the management of dandruff?-an
2011;4:32-38. overview. Egypt Dermatol Online J 2009;5:8.
8. Schmidt-Rose T, Braren S, Flster H, Hillemann T, Oltrogge 24. Gokulshankar S, Ranjith MS, Sumithira, Ranganathan S,
B, Philipp P, et al. Efficacy of a piroctone olamine/climbazol Manuel F, Mohanty BK. Factors determining the
shampoo in comparison with a zinc pyrithione shampoo in antidandruff effect of climbazole in a shampoo formulation.
subjects with moderate to severe dandruff. Int J Cosmet Sci J Appl Cosmetol 2011;29:135-140.
2011;33:276-282. 25. Crespo Erchiga V, Ojeda Martos AA, Vera Casao A,
9. Barac A, Pekmezovic M, Milobratovic D, Otasevic-Tasic S, Crespo Erchiga A, Snchez Fajardo F. Isolation and
Radunovic M, Arsic Arsenijevic V. Presence, species distri- identification of Malassezia spp. In pytiriasis versicolor,
bution, and density of Malassezia yeast in patients with seborrheic dermatitis and healthy skin. Rev Iberoam Micol
seborrhoeic dermatitis-a community-based case-control study 1999;16:S16-S21.
and review of literature. Mycoses 2015;58:69-75. 26. Sandstrm Falk MH, Tengvall Linder M, Johansson C,
10. Leeming JP, Notman FH. Improved methods for isolation Bartosik J, Bck O, Srnhult T, et al. The prevalence of
and enumeration of Malassezia furfur from human skin. J Malassezia yeasts in patients with atopic dermatitis,
Clin Microbiol 1987;25:2017-2019. seborrhoeic dermatitis and healthy controls. Acta Derm
11. Sugita T, Tajima M, Ito T, Saito M, Tsuboi R, Nishikawa A. Venereol 2005;85:17-23.
Antifungal activities of tacrolimus and azole agents against 27. Gupta AK, Kohli Y, Summerbell RC, Faergemann J.
the eleven currently accepted Malassezia species. J Clin Quantitative culture of Malassezia species from different
Microbiol 2005;43:2824-2829. body sites of individuals with or without dermatoses. Med
12. Dessinioti C, Katsambas A. Seborrheic dermatitis: etiology, Mycol 2001;39:243-251.
risk factors, and treatments: facts and controversies. Clin 28. Tajima M, Sugita T, Nishikawa A, Tsuboi R. Molecular
Dermatol 2013;31:343-351. analysis of Malassezia microflora in seborrheic dermatitis
13. Heng MC, Henderson CL, Barker DC, Haberfelde G. patients: comparison with other diseases and healthy
Correlation of Pityosporum ovale density with clinical subjects. J Invest Dermatol 2008;128:345-351.
severity of seborrheic dermatitis as assessed by a simplified 29. Patio-Uzctegui A, Amado Y, Cepero de Garca M, Chaves
technique. J Am Acad Dermatol 1990;23:82-86. D, Tabima J, Motta A, et al. Virulence gene expression in
14. Schwartz RA, Janusz CA, Janniger CK. Seborrheic dermatitis: Malassezia spp from individuals with seborrheic dermatitis.
an overview. Am Fam Physician 2006;74:125-130. J Invest Dermatol 2011;131:2134-2136.
15. Schwartz JR, Messenger AG, Tosti A, Todd G, Hordinsky M, 30. Lee YW, Byun HJ, Kim BJ, Kim DH, Lim YY, Lee JW, et al.
Hay RJ, et al. A comprehensive pathophysiology of dandruff Distribution of malassezia species on the scalp in korean
and seborrheic dermatitis-towards a more precise definition seborrheic dermatitis patients. Ann Dermatol 2011;23:
of scalp health. Acta Derm Venereol 2013;93:131-137. 156-161.

738 Ann Dermatol


Efficacy and Safety of C/P Cream for Facial SD

31. Oh BH, Lee YW, Choe YB, Ahn KJ. Epidemiologic study of 32. Ro BI, Dawson TL. The role of sebaceous gland activity and
Malassezia yeasts in seborrheic dermatitis patients by the scalp microfloral metabolism in the etiology of seborrheic
analysis of 26S rDNA PCR-RFLP. Ann Dermatol 2010;22: dermatitis and dandruff. J Investig Dermatol Symp Proc
149-155. 2005;10:194-197.

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