American Journal of Clinical and Experimental Medicine
`2016; 4(3): 76-80
`http://www.sciencepublishinggroup.com/j/ajcem
`doi: 10.11648/j.ajcem.20160403.17
`ISSN: 2330-8125 (Print); ISSN: 2330-8133 (Online)
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`77
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`Ma’arifah Nadjar et al.: The Effectiveness of Benzoyl Peroxide 5% Gel with 0.05% Tretinoin Gel in
`Patients with Mild Acne Vulgaris (Identification of P. Acnes)
`
`
`
`causing the formation of papules and pustules which
`exacerbate the disease severity. When formed, papules or
`pustules can develop into nodules or cysts. [3]
`The average age to suffer from acne is 11 years old in
`females and 12 years old in males. Acne affects males more
`often in teenager age. A study suggests that acne affects 56%
`of males and 45% of females of 14-16 years old with
`moderate to severe degee in 11%. [4]
`Etiology of acne vulgaris
`is not well understood.
`Pathogenesis of acne is a multifactorial process in the
`phylocebaceous gland which enable the bacteria to develop
`and form inflammations. There are 4 steps to identify the
`acne: follicular epidermal hyperproliferation, excessive
`sebum production,
`inflammation,
`and
`activation of
`propionibacterium acnes. Each of this processes are related
`each other and under the hormonal and immune system
`effects. [1]
`Management of acne vulgaris varies depending on the type
`and severity of acne lesions. In mild type, the most
`appropriate treatment is topical treatment. Topical treatment
`is indicated for comedonal acne and mild to moderate
`papulopustular acne without scar. The topical agents included
`tretinoin, antimicrobial and antibacterial agents. The
`application is 4-8 weeks before chaging the regimen. [5]
`
`2. Patient and Methods
`
`This study was a double blind clinical trial. This study was
`conducted in Dermatology and Venereology Polyclinic of
`Wahidin Sudirohusodo Hospital, Hasanuddin Teaching
`Hospital, Necri Laboratory of Hasanuddin Hospital,
`
`3. Result
`
`conducted during Januari 2016 to February 2016. Study
`population consisted of 40 female with mild acne vulgaris
`patients aged 15-20 years old. These acne patients are based
`on combined acne severity classification (2002). Patients
`agreed and signed the informed consent form. Patients did
`not have topical treatment history in 2 weeks, not using
`antibiotic and anti-inflammation in the last 2 weeks, not
`currently having other skin diseases on face such as allergic
`contact dermatitis, ready to participate in evaluation and
`treatment as per study procedures and follow the control
`schedule according to study plan, and ready to participate in
`this study until the end of the study.
`Data were collected by: 1) Interview/history taking, 2)
`physical evaluation by observing the clinical signs of acne
`vulgaris in facial area, and then calculating the papule and
`pustule number, and determining the acne degree by using
`combined acne severity classification on right-hand half face
`and then on left-hand half face and then the face of patients
`were photographed in straight sitting position, from front
`direction, left and right direction, 3) Measuring the sebum
`level using sebumeter in mild acne vulgaris patients (left and
`right side) by paying attention to the T and U area. Patients
`were followed-up (week 2, 4, and 6), 4) PCR evaluation with
`DNA extraction and electrophoresis of PCR result, (5)
`Application of benzoyl peroxide 5% gel and tretinoin 0.05%
`gel.
`The collected data were processed using SPSS version
`17.0. Analysis hypothetical test by Uji Mann-Whitney Test
`and Chi-Square Test. Hypothesis was accepted when the p
`value <0.05.
`
`Table 1. Comparison of PCR results between benzoyl peroxide 5% gel and Tretinoin 0,05% gel before treatment.
`
`Group
`
`Pre benzoyl peroxide 5% gel
`
`Pre Tretinoin 0,05% gel
`
`Total
`
`Note: Chi-Square Test.
`
`PCR
`
`Positive
`
`11 (55%)
`
`9 (45%)
`
`20 (50%)
`
`Negative
`
`9 (45%)
`
`11 (55%)
`
`20 (50%)
`
`Total
`
`p value
`
`20 (100%)
`
`20 (100%)
`
`40 (100%)
`
`0.527
`
`Table 1 shows positive PCR results in 20samples (100%), and negative PCR results in 20 samples (100%).
`
`Table 2. Comparison of sebum level of acne vulgaris patients between benzoyl peroxide 5% gel grup and tretinoin 0.05% gel group at day 0, day 14, day 28
`and day 42.
`
`Day
`
`Day 0
`
`Day 14
`
`Day 28
`
`Day 42
`
`n
`
`40
`
`40
`
`40
`
`40
`
`Sebum Level (ug/cm-2)
`
`benzoyl peroxide 5% gel Median (min-max) n= 20
`
`Tretinoin 0.05% gel Median (min-max) n= 20
`
`77.6(4.2-198)
`
`86.1 (26.2-201)
`
`64.7 (35.2-213.8)
`
`47.5 (21-138)
`
`84.5 (46-194)
`
`63.6 (28.8-194)
`
`61.5 (24.6-180.4)
`
`61.9 (27.6-140)
`
`Difference
`
`p
`
`6.9
`
`22.5
`
`3.2
`
`14.4
`
`0.646
`
`0.402
`
`0.291
`
`0.176
`
`Note: Mann-Whitney test, Normality Test= Shapiro-wilk.
`
`Table 2 shows the comparison of sebum level of mild acne vulgaris patients between benzoyl peroxide 5% gel and tretinoin
`0.05% gel application at day 0 to day 42, with no significant difference (p<0.05).
`
`Strathclyde Ex. 2024, p. 2
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`American Journal of Clinical and Experimental Medicine 2016; 4(3): 76-80
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`78
`
`Table 3. Comparison of Comedone Number of Acne Vulgaris Patients with Benzoyl Peroxide 5% Gel and Tretinoin 0.05% Gel Treatment.
`
`Day
`
`Day 0
`Day 14
`Day 28
`Day 42
`
`n
`
`40
`40
`40
`40
`
`Comedone Number
`Benzoyl peroxide 5% gel Median (min-max) n= 20 Tretinoin 0.05% gel Median (min-max) n= 20
`19(10-19)
`19(9-19)
`18.5(10-19)
`19 (10-19)
`11.5 (7-19)
`19 (4-19)
`10 (5-19)
`19 (4-19)
`
`Difference
`
`p
`
`0
`0.5
`7.5
`9
`
`0.405
`0.040
`0.002
`0.001
`
`Note: Mann Whitney Test, Normality Test = Shapiro-wilk.
`
`Table 3 indicates the comparison of comedone number of mild acne vulgaris patients between the benzoyl peroxide 5% gel
`and tretinoin 0.05% gel treatment at day 0, day 14, day 28 and day 42, with p < 0.05 only at day 14 and day 28.
`
`Table 4. Comparison of Papule Number of Acne Vulgaris Patients with Benzoyl Peroxide 5% Gel and Tretinoin 0.05% Gel Treatment.
`
`Day
`
`Day 0
`Day 14
`Day 28
`Day 42
`
`n
`
`40
`40
`40
`40
`
`Papule number
`Benzoyl Peroxide 5% gel Median (min-max) n= 20
`9.5(3-14)
`9(2-14)
`6 (1-12)
`3 (0-10)
`
`Tretinoin 0.05% gel Median (min-max) n= 20
`12(4-15)
`11 (2-14)
`9.5 (2-14)
`8 (2-14)
`
`Difference
`
`p
`
`2.5
`2
`3.5
`5
`
`0.035
`0.122
`0.122*
`0.330
`
`Note: Mann Whitney test, Normality test= Shapiro-wilk, *t-test.
`
`Table 4 shows the comparison of papule number of mild acne vulgaris patients between benzoyl peroxide 5% gel and
`tretinoin 0.05% gel treatment at day 0, day 14, day 28, and day 42. Only day 0 that indicates significant results (p<0,05).
`
`Table 5. Comparison of Pustule Number in Acne Vulgaris patients with benzoyl peroxide 5% gel and tretinoin 0.05% gel treatment.
`
`Day
`
`Day 0
`Day 14
`Day 28
`Day 42
`
`n
`
`40
`40
`40
`40
`
`Pustule Number
`Benzoyl peroxide 5% gel Median (min-max) n= 20
`1(0-8)
`1(0-6)
`1 (0-3)
`0 (0-3)
`
`Tretinoin 0.05% gel Median (min-max) n= 20
`2(0-8)
`1.5 (0-7)
`2 (0-9)
`1 (0-6)
`
`Difference
`
`p
`
`1
`0.5
`1
`1
`
`0.330
`0.311
`0.210
`0.072
`
`Note: Mann Whitney test, Normality Test = Shapiro-wilk.
`
`Table 5 indicates the comparison of pustule number in mild acne vulgaris between benzoyl peroxide 5% gel and tretinoin
`0.05% gel treatment at day 0, day 14, day 28 and day 42, with no significant difference (p<0.05).
`
`Table 6. Side effect in benzoyl peroxide 5% gel and tretinoin 0.05% gel treatment before and after treatment.
`
`Side Effect
`
`Erythema
`Pruritus
`Painful
`Exfoliative
`Dryness
`Burning sensation
`None
`
`Median (min-max)
`Benzoyl peroxide 5% gel n (20)
`4(33.3%)
`9(42.9%)
`5(29.4%)
`6(30.0%)
`2(18.2%)
`0(0%)
`3(37.5%)
`
`Note: Linear Test, (*) uji Fisher’s exact test.
`
`
`Tretinoin0.05% gel n(20)
`8(66.7%)
`12 (57.1%)
`12(70.6%)
`14(70.0%)
`9(81.8%)
`2(100.0%)
`5(62.5%)
`
`n
`
`12
`21
`17
`20
`11
`2
`8
`
`p
`
`0.173
`0.348
`0.027
`0.012
`0.014
`0.487*
`0.695*
`
`Table 6 indicates the significant side effects observed,
`including the painful, exfoliative, and dryness side effects,
`where p < 0.05. More than one side effect were observed in
`some patients.
`
`4. Discussion
`
`Acne vulgaris is a common inflammatory disease of parts
`of follicle pilosebaseus. The disease is characterized by
`lesions varying in severity from open and closed comedones
`on the face, in mild cases are comedones, papules, nodules,
`
`and cysts either on the face or body in severe disease. [6]
`The findings of this study indicate that from 40 samples of
`patients with mild acne vulgaris that had been evaluated by
`PCR, there is no significant difference between groups
`treated with benzoyl peroxide 5% gel and tretinoin 0.05%
`gel. It was found that 11 patients in benzoyl peroxide 5% gel
`group were PCR positive, and 9 patients in tretinoin 0.05%
`gel group were PCR positive. Polymerase chain reaction is an
`enzymatic method
`to
`amplify DNA
`in
`vitro.
`Propionibacterium acnes (P. acnes) is a commensal organism
`on skin playing role as an opportunist pathogen. P. acnes is
`
`Strathclyde Ex. 2024, p. 3
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`

`

`79
`
`Ma’arifah Nadjar et al.: The Effectiveness of Benzoyl Peroxide 5% Gel with 0.05% Tretinoin Gel in
`Patients with Mild Acne Vulgaris (Identification of P. Acnes)
`
`
`
`not considered to be infectious but it has a role in the
`development of acne, with important factors that include
`micro-environment of the follicle causing the bacterial
`colonization into follicle duct and resulting in inflammation.
`There is a relationship between p. acnes reduction and acne
`clinical improvement. This P. acnes reduction is related to
`proinflammatory mediators reduction. Host response to
`inflammatory stimulus seems to explain the variation of
`inflammation intensity. [7] P. acnes is found in both acne
`affected and normal hair follicles along with other skin
`commensals such as Staphylococcus aureus and Malassezia
`spp. Although present in healthy and diseased follicles, it
`may be a matter of the threshold number of bacterial cells
`that are required to cause disease. [8] In these mild acne
`vulgaris patients, the PCR is sequenced to make sure if the
`produced sample had been accurate in showing P.acnes. The
`discovery and benefits of this PCR technique has a wide
`impact on science and technological development in acne
`vulgaris, particularly in dermatology field.
`Patients in 15-16 years old category with benzoyl peroxide
`5% gel treatment were 13 patients (48.1%) and with tretinoin
`0.05% gel were 14 patients (51.9%). Patients in 17-18 years
`old category with benzoyl peroxide 5% gel treatment were 7
`patients (53.8%), and with tretinoin 0.05% gel treatment
`were 6 patients (46.2%). Benzoyl peroxide 5% gel is
`generally well tolerated with minimum side effects. [9]
`Tretinoin 0.05% gel has been approved by FDA for use in
`children above 10 years old. The safety and efficacy of this
`agent have been documented in a large scale trial with
`pediatric patients between 12 to 18 years old. Topical retinoid
`has been widely used in this age group. [10]
`Comparison of sebum level of patients with mild acne
`vulgaris between BPO 5% gel and tretinoin 0.05% gel
`treatment at day 0 to day 42 indicated no significant
`difference. Sebum is a complex mixture of triglyceride, ester
`wax, squelene, and minority of cholesterol and phospholipid.
`Abnormality in sebum content is considered one of the some
`factors invelved in acne pathogenesis, with good role in
`comedogenesis or in inflammatory reaction development that
`cause acne lesions clinicaclly. Production and secretion of
`sebum is a vital condition in acne vulgaris, even though the
`hipersecretion is not enough to initiate the development of
`lesion. However, sebum in acne patients are different,
`quantitatively and qualitatively, from sebum in patients with
`normal skin. [11] Tretinoin works by reducing the sebaceous
`gland activities, which reduces sebum production. Sebum
`reduction reduces the propionibacterium acnes development,
`accummulated in fatty acid in sebum. [12]
`Comparison of comedone number of patients with mild
`acne vulgaris between benzoyl peroxide 5% gel and tretinoin
`treatment at day 14, 28, and 42 indicated a significant
`difference. The comparison of papule number of patients
`with mild acne vulgaris between benzoyl peroxide 5% gel
`and tretinoin 0.05% gel treatment indicated a signicant
`results only at day 0. Comparison of pustule number of
`patients with mild acne vulgaris between benzoyl peroxide
`5% gel and tretinoin 0.05% gel at day 0 to day 42 indicated
`
`no significant difference. Benzoyl peroxide has a keratolytic
`and anti-inflammatory effect which contribute to its clinical
`effectiveness due to lyphophylic properties, penetrating into
`stratum corneum and degraded into benzoic acid and
`hydrogen peroxide. [13] Tretinoin increases the cells turn
`over in skin surface, which can reduce the formation of
`hyperkeratinized plaque and microcomedone. [12]
`Benzoyl Peroxyde (BPO) is a non-antibiotic antibacterial
`used as an effective treatment in mild to moderate acne
`vulgaris. This agent can be applied 1 to 2 times a day, with
`preparations that include lotion, cream, gel, foam, solution, at
`concentration of 1%, 2.5%, 4%, 5%, and 10%. The
`mechanism of this agent is to kill bacterium by oxidating the
`given cell membrane, at its antimicrobial activities. Several
`studies suggest that BPO has a keratolytic effect and anti-
`inflammatory that contribute to its clinical effectivenesss due
`to its lypophylic properties. BPO penetrates into stratum
`corneum and damaged into benzoic acid and hydrogen
`peroxide [13]
`BPO is effective as topical antibiotic in the treatment of
`inflammatory and non-inflammatory acne lesion therapy.
`Several studies have shown that BPO is effective in reducing
`inflammatory and non-inflammatory lesions, BPO has a fast
`action onset, good efficacy and generally weel tolerated, and
`no bacterial resistance to BPO. BPO can be applied 1 to 2
`times a day (morning and night). [3] Some studies have
`implicated the use of benzoyl peroxide at concentration of
`5% for mild acne vulgaris treatment with 30% of lesion
`reduction. [14] Resistance can be prevented by avoiding the
`use of antibiotic monotherapy,
`limiting
`the
`length of
`antibiotic use, and the use of antibiotics along with benzoyl
`peroxide if possible. [15]
`Topical retinoid is appropriate for maintenance treatment.
`Topical
`retinoid
`reacts
`against
`the
`comedone
`(macrocomedone and microcomedone) and has a direct anti-
`inflammatory effect. [16] The action mechanism of topical
`retinoid is by preventing the comedone development (anti-
`comedogenic)
`and healing
`the
`existing
`comedone
`(comedolytic), Retinoid acid activate the nuclear retinoid
`acid receptors, where it increases the tur over of follicular
`epithelial cells and recovering the abnormal desquamation,
`reduce comedogenesis and
`trigger
`the
`resolution of
`comedone development. Several studies have suggested that
`topical retinoid has a direct effect as anti-inflammatory agent
`that
`is
`related
`to non-specific
`immunity modulation,
`including
`the TLR2
`receptor
`reduction,
`inflammation
`mediator, and change the inflammatory cell activity. [13] The
`most common side effect is pruritus om 21 patients (9
`[42.9%] in benzoyl peroxide 5% gel group and 12 [57.1%] in
`tretinoin 0.05% gel group. Whereas the exfoliative skin was
`observed in 20 patients (6 [30%] in benzoyl peroxide 5% gel
`group and 12 [70.6%] in tretinoin 0.05% group. The side
`effects of bezoyl peroxide included skin irritation (dryness,
`stinging
`sensation, burning
`sensation, erythema, or
`exfoliative skin). [3] The most frequent side effect of retinoid
`topical was local irritation, including erythema, dryness,
`burning sensation, exfoliation and pruritus. [13]
`
`Strathclyde Ex. 2024, p. 4
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`

`

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`American Journal of Clinical and Experimental Medicine 2016; 4(3): 76-80
`
`
`80
`
`5. Conclusions
`
`This study concludes that benzoyl peroxide 5% gel and
`tretinoin 0.05% gel have the same effectiveness in patients
`with mild acne vulgaris. However, benzoyl peroxide 5% gel
`is faster in reducing comedone, papule or pustule compared
`to tretinoin 0.05% gel. Decreased sebum level indicated no
`significant difference between benzoyl peroxide 5% gel and
`tretinoin 0.05% gel. P. acnes were found in patients with mild
`acne vulgaris before the administration of benzoyl peroxide
`5% gel and tretinoin 0.05% gel, although not in all samples.
`
`Contraceptives In Acne Vulgaris. J Am Acad Dermatol. 2014;
`1-9.
`
`[7] Gollnick H. & Cunliffe W. Management of acne are report
`from a global alliance to improve outcome in acne. J Am Acad
`Dermatol. 2003; 49: S1-38.
`
`from
`[8] Achermann Y. et al. Propionibacterium acnes:
`Commensal to Opportunistic Biofilm-Associated Implant
`Pathogen. Clinical Microbiology Reviews J. 2014; 27: 419–
`440.
`
`[9] Ramanathan S. and Hebert A. A. Management of acne
`vulgaris. J pediatr Health Care. 2011; 25: 332-337.
`
`References
`
`
`
`[10] Eichenfield L. F. et al. Evidence-Based Recommendations for
`the Diagnosis and Treatment of Pediatric Acne. Acad Pe J.
`2013; 131, 163-182.
`
`[1] Zaeglein A. et al. Acne vulgaris and acneiform eruptions. In
`wolf, K. Goldsmith, L, Katz, S. Gilchrest, B, Paller, A. &
`Leffell, D. Eds. Fitzpatrick’s dermatology in general medicine.
`New York. 8th ed. 2012. 1264-1290.
`
`[2] Zaenglein, A. L. Thiboutot, D. M. Acne vulgaris.
`Dermatology. J. L. Bolognia, J. L. Jorizzo and J. V. Schaffer.
`USA, elsevier. 2011; 36: 545-559.
`
`[3] Benner N. & Sammons D. Overview of the treatment of acne
`vulgaris. Osteophatic Fam Physician J. 2013; 5: 185-190.
`
`[4] Layton A. M. Disorders of the Sebaceous Glands. Burns T.
`Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of
`Dermatology. 8th ed. Wiley-Blackwell. 2010. p. 42. 17-42.55.
`
`[5] Kraft, J., Freiman, A. Management of Acne. Canadian
`Medical Association J. 2011; 183 (7): 430-435.
`
`[6] Koo, E, B., Petersen, T, D, Kimball, A. B. Meta-Analysis
`Comparing Efficacy Of Antibiotics Versus Oral
`
`
`[11] Pappas, A., Johnsen, S., Liu, C. J. Eisinger, M. Sebum
`analysis Of Individuals with and without Acne. Dermato-
`endocrinology. 2009; 1: 3. 157-161.
`
`[12] Wolff K. et al. Topical tretinoin, Fitzpatrick's Dermatology in
`General Medicine, Ac. 2008; 3789-3797.
`
`[13] Malhotra N, et al. Real World Acne Therapy in Primary Care.
`Dermatol J. 2012; 5: 29-43.
`
`[14] Liao DC. Management of Acne. Fam J Pract. 2003; 52: 43.
`
`[15] Ramdani R, 1 Sibero, H. T. Treatment for Acne Vulgaris. J
`Majority. 2015; 4: 87-95.
`
`[16] Tsatsou F. & Christos. C. Z Acne vulgaris. Treatment of Skin
`Disease: Comprehensive Therapeutic Strategies. M. G.
`Lebwohi, W. R. Heymann, J. B.-. jones and I. Coulson. New
`York, Elsevier. 3. 2014. 6-11.
`
`Strathclyde Ex. 2024, p. 5
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`