Outcome of Adapalene and Isotretinoin in the Treatment of Acne Vulgaris

Topical application of Isotretinoin and Adapalene has proved may begin a new era of treatment with low-irritant retinoids. It seems that, Adapalene treatment is a good choice for topical treatment of acne vulgaris with less side effects and high efficacy. Adapalene should be described as first line for treatment of acne vulgaris.


INTRODUCTION
Acne is an extremely common skin disease, and thus, individuals have various beliefs and perceptions about its treatment methods. In a recent community-based study, 68% of male and 66.8% of female teenage participants were reported to have acne [1].
Although less frequently encountered than in adolescence, a significant number of adults, and 20 years of age or older, also have acne [1]. In many cases, acne is regarded as a physiologic phenomenon, which is likely to regress spontaneously after adolescence. However, in some individuals, acne persists and substantially increases the likelihood of scarring [2]. Because acne is a common skin condition, it has a great impact on quality of life. Thus, a detailed understanding of its more general aspects is important [3]. Numerous clinical research studies have been undertaken on its epidemiology in western countries [1,4,5].
However, comparatively few have been undertaken in African and Asian populations [6,7]. Acne is usually diagnosed by the patient. The physician needs to determine if the condition is non-inflammatory (open and closed comedons), inflammatory (papules or pustules) or a mixture of both, the most common situation.
Topical treatment is sufficient in most patients with acne, but systemic therapy is required in patients who have acne nodules and cysts [4]. Topical retinoids such as Tretinoin, Isotretinoin, or Adapalene are effective in many patients with comedonal acne.
Adapalene is a topical retinoid derived from naphthoic acid with a selective effect on the epidermis. It is indicated for treatment of acne vulgaris, alone or with other anti-actinic topicals. It displays comedolytic and anti-inflammatory activities.
Topical retinoids are comedolytic and antiinflammatory. They normalizefollicular hyperproliferation and hyperkeratinization. They reduce the numbers of microcomedones, comedons, and inflammatory lesions and may be used alone or in combination with other acne medications. The most commonly prescribed topical retinoids for acne vulgaris include Adapalene, Tazarotene, and Tretinoin. These retinoids should be applied once daily to clean, dry skin, but they may need to be applied less frequently if irritation occurs [9]. Skin irritation with peeling and redness may be associated with the early use of topical retinoids. Alternate-day dosing may be used ifirritation persists. Topical retinoids thin the stratum corneum, and they have been associated with sun sensitivity. So patients should be instructed about sun protection [8]. Retinoids are used in the treatment of many diverse diseases and are effective in the treatment of a number of dermatological conditions such as inflammatory skin disorders, skin cancers, disorders of increased cell turnover as psoriasis, and photoaging [9].
Adapalene is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne and is also used (off-label) to treat keratosis pilaris as well as other skin conditions [10].
Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased [11]. Application of Adapalene gel to the skin 3-5 minutes before application of clindamycin enhances penetration of clindamycin into the skin, which may enhance the overall efficacy of the treatment as compared to clindamycin alone [12].
Unlike tretinoin (Retin-A), Adapalene has also been shown to retain its efficacy when applied at the same time as benzoylperoxide due to its more stable chemical structure [8,9]. Adapalene in small concentrations is a moderator of cellular differentiation, keratinization, and inflammatory processes. It has both exfoliating and antiinflammatory effects. The exact mode of action of Adapalene is unknown.
Adapalene is applied topically to the skin, and its absorption into the blood through this medium is very low. Only trace amounts of Adapalene have been found in the plasma of chronically treated patients [13].
Tretinoin is all-trans stereoisomer of retinoic acid, used topically for treatment of cases of acne vulgaris in which comedons, pustules, and papules predominate; it prevents comedons formation and suppresses keratin synthesis; common adverse effects are erythema and desquamation. It is also administered orally in treatment of acute [13].
In a Pakistani clinical study conducted by Iftikhar et al. Adapalene cream 0.1% was compared against Isotretinoin 0.05% in the treatment of acne vulgaris. The study targeted comparing efficacy and tolerability of Adapalene cream 0.1% and Isotretinoin cream 0.05% in the treatment of acne vulgaris [14].
Both Adapalene and Isotretinoin demonstrated comparable efficacy. However, significantly lower skin irritation was noted with Adapalene.
The only frequent adverse event is a mild skin irritation during the first two weeks of treatment.

Objective
The present study was undertaken to compare the efficacy and tolerability of Adapalene cream 0.1% and Isotretinoin cream 0.05% in the treatment of acne vulgaris of the face.

MATERIALS AND METHODS
This is an observational, cross-sectional hospitalbased study included the both genders attended Khartoum Teaching Dermatology Hospital with acne vulgaris from September 2010 to September 2011. Pregnant women, breast feeding women and patients on a previous treatment have been excluded

Sample Size
According to the Equation: Where: N= Sample size. Z = constant 1.96 2 P = Prevalence = 10% Q = (1-P). D = allowable error = 4% It was determined to be 90 patients, but 100 patients of mild to moderate acne irrespective of age, sex and social status were enrolled. After an informed consent, a detailed history was taken and scrupulous physical examination was performed in each patient.
Patients were randomized into two groups A and B (fifty patients for each). The randomized process was conducted by asking the patient to take folded paper contained the A or B letter and then the patient would be enrolled in Adapalene or Isotretinion group. Patients in group A applied Adapalene cream 0.1% and group B used Isotretinoin cream 0.05% once daily at night for 6 weeks. Quantity of cream remained the same i.e. equivalent to size of half a pea.
All patients were clinically diagnosed. Efficacy variables included non-inflammatory, inflammatory lesions and total lesion counts; global grade; and global assessment of improvement in acne severity. Skin tolerability variables that were known to be associated with topical retinoid derivatives included erythema, desquamation (scaling), dryness, pruritus, and stinging/ burning, thus the presence of any of them during the course of treatment have been accounted as a drug intolerability indicator. During period of follow-ups we encouraged our patients to mention any symptoms concomitant with our regular reexaminations. Demographic data collected by direct interviewing to the intended subjects and clinical examination was done according to the attached questionnaire.
Data was analyzed by Statistical Package for Social Sciences (SPSS), version 10, t-test used to compare quantitative variables (score of nonmedical treatment according to socioeconomic status). Analysis of variance ANOV A was used to compare score of nonmedical treatment according to education level.
Chi-squared test was used to determine the statistical significances of association between qualitative variables. Test was considered significant, when P. value is less than 0.05.

RESULTS
Fifty patients were treated with Adapalene and fifty were treated with Isotretinoin. The means age of Adapalene and Isotretinoin groups were 27.42±10.15 and 24.28±7.92.
The gender distribution of Adapalene and Isotretinoin groups, in both groups the percentage of males was 22% and female 78%. Among Adapalene group the mild cases were 36% and moderate cases were 64%, while among Isotretinoin group, the mild cases were 18% [9] and the moderate were 82%. Cases with inflammatory lesions were 62% of Adapalene groups, while 76% were of Isotretinoin groups.
Analysis indicated that Adapalene cream was significantly (P < 0.01) more effective in treating acne than Isotretinoin gel after 3 and 6 weeks from treatment. After 3 weeks of treatment with Adapalene 2% was cured, 94% were improved and 4% were not improved, while within Isotretinoin group 2% was cured, 46% were improved and 52% were not improved. After 6 weeks of treatment with Adapalene 90% was cured and 10% were improved, while within Isotretinoin group 8% was cured, 50% were improved and 42% were not improved. After 6 weeks of treatment with Adapalene 28% of cases had lesions, while among Isotretinoin group they were 84%.  Acne improvement according to type of drug used after 3 weeks

After 3 weeks Cured
After 3 weeks Improved

After 3 weeks Not Improved
After 6 weeks Cured After 6 weeks Improved After 6 weeks Not Improved

DISCUSSION
Acne vulgaris is a chronic, inflammatory disease of the pilosebaceous unit, that affects seborrhoeic areas like face, back, and chest and characterized by comedons, papules, pustules, nodules, cysts, and scars. Almost every individual has some degree of acne during puberty with spontaneous resolution occurring in early adult life. Occasionally, the disea into the fourth decade or even remains a lifelong problem. Because of the involvement of the face with considerable cosmetic problems, acne is a major psychosocial problem for many teenagers and young adults [15][16][17].
The treatment of acne vulgaris is not curative. The purpose is to reduce discomfort due to inflamed lesions, to improve the appearance, and to prevent scars. Acne management is a long term treatment and requires patience. The patient should be informed on the issue Topical treatment of acne vulgaris has changed over the years. Agents containing sulphur or resorcinol were used in especially first part of 20 th century. Salicylic acid which is a keratolytic agent was popular in some time. Nowadays, the most popular topical agents were retinoids, 7

Lesions after treatment among adapalene and Isotretinoin group
Acne vulgaris is a chronic, inflammatory disease of the pilosebaceous unit, that affects areas like face, back, and chest and characterized by comedons, papules, pustules, nodules, cysts, and scars. Almost every individual has some degree of acne during puberty with spontaneous resolution occurring in early adult life. Occasionally, the disease persists into the fourth decade or even remains a lifelong problem. Because of the involvement of the face with considerable cosmetic problems, acne is a major psychosocial problem for many teenagers aris is not curative. The purpose is to reduce discomfort due to inflamed lesions, to improve the appearance, and to prevent scars. Acne management is a longterm treatment and requires patience. The patient should be informed on the issue [15,18]. al treatment of acne vulgaris has changed over the years. Agents containing sulphur or resorcinol were used in especially first part of century. Salicylic acid which is a keratolytic agent was popular in some time. Nowadays, the ents were retinoids, benzoyl peroxide, azelaic acid, and topical antibiotics [19].
Topical application of Isotretinoin and Adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages and less irritancy over tretinoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors.
Theobjectives of this study were to compare the efficacy and tolerability of Adapalene cream0 and Isotretinoin cream 0.05% in the treatment of acne.
Result indicated that both Adapalene cream 0.1% and Isotretinoin are effective in treating acne. However Adapalene was found significantly more effective than Isotretinoin 6 weeks of treatment all patient (Mild and Moderate) treated with Adapalene were either cured or improved, while among Isotretinoin group 42% of patients were not improved and 50% improved. Patients remained with lesions after 6 weeks of treatment among Adapalene group were significantly lesser than among Isotretinion group. This result with agrees with previous studies by Ioannides et al 28.00%

84.00%
; Article no. BJMMR.22385 Isotretinoin group benzoyl peroxide, azelaic acid, and topical Topical application of Isotretinoin and Adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages inoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors. of this study were to compare the ene cream0.1% 05% in the treatment of Result indicated that both Adapalene cream 1% and Isotretinoin are effective in treating acne.
However Adapalene was found significantly more effective than Isotretinoin, After 6 weeks of treatment all patient (Mild and Moderate) treated with Adapalene were either cured or improved, while among Isotretinoin group 42% of patients were not improved and 50% improved. Patients remained with lesions among Adapalene group were significantly lesser than among Isotretinion group. This result with agrees with et al. [20] and

Lesions
Ahmed et al. [21]. All these studies ensured the efficacy of Adapalene in comparison with other different retinoids.
The study demonstrated that Adapalene has faster effect than Isotretinoin. After 3 weeks of treatments 96% of patients treated with Adapalene were either cured or improved, while among Isotretinoin group the percentage was 48%. The faster onset of action of Adapalene was also recorded by considering the safety and tolerability and like many previous studies [20,21] Adapalene showed significantly higher safety and tolerability concomitant with Iftikar [14]. The safety and tolerability was assessed depending on the degree of scaling, erythema, burning sensation and pruritus. This anti-inflammatory effect is due to inhibition of the lipooxygenase activity and also to oxidative metabolism of arachidonic acid. These mechanisms may be the reason for decreased risk of irritation with Adapalene. Adapalene has a very low percutaneous absorption once the drug has penetrated the stratum corneum, so that it becomes entrapped in the epidermis and hair follicle, which are targeted areas. Only trace amounts (0.25 ng/ml) of parent substance have been found in the plasma of acne patients following chronic topical application of Adapalene in controlled trials. Excretion appears to be primarily by the biliary route. Erythema, peeling, dryness and burning are the most frequent encountered side effects accorded with Millikan results [22].

CONCLUSIONS
The purpose of treatment of acne vulgaris is to reduce discomfort due to inflamed lesions, to improve the appearance, and to prevent scars. Both Adapalene cream 0.1% and Isotretinoin are effective in treating acne, however Adapalene was found significantly more effective than Isotretinoin. Adapalene has faster onset of action of, which reflect on patients psychologically in term of improvements, comforts and good appearance. Significantly lower skin irritation was noted with Adapalene, indicating that Adapalene may begin a new era of treatment with low-irritant retinoids.

RECOMMENDATIONS
Adapalene treatment is a good choice for topical treatment of acne vulgaris with less side effects and high efficacy. Adapalene should be described as first line for treatment of acne vulgaris.

ETHICAL APPROVAL
The purpose of the study was explained to the participants and verbal informed consent was obtained, in addition to considering privacy of participants. The ethical clearance was granted from the Sudanese Medical Specialization Board Ethical committee.