Indian Journal of Drugs in Dermatology

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 5  |  Issue : 1  |  Page : 19--25

A comparative study between topical adapalene (0.1%) versus a combination of topical adapalene (0.1%) and intense pulsed light therapy in the treatment of inflammatory and noninflammatory facial acne vulgaris: A split-face randomized controlled trial


Shah Karan, Jadhav Vikrant, Gugle Anil 
 Department of Dermatology, Dr. Vasantrao Pawar Medical College, Nashik, Maharashtra, India

Correspondence Address:
Dr. Jadhav Vikrant
Maitreya, Plot No. 29, Kalpataru Nagar, Ashoka Marg, Nasik - 422 011, Maharashtra
India

Abstract

Introduction: Acne vulgaris is a common dermatological disorder encountered in dermatology practice. Various treatment modalities are available for acne. Lasers and light-based therapies are also gaining popularity with good clinical results. The choice of treatment depends on the type and severity of acne. Aims:(1) To evaluate the efficacy and safety of topical adapalene (0.1%) gel in facial acne vulgaris. (2) To evaluate the efficacy and safety of topical adapalene (0.1%) gel in combination with intense pulsed light (IPL) in facial acne vulgaris. (3) To compare the above results. Materials and Methods: A total of 50 patients with facial acne were included. IPL device equipped with an acne treatment filter emitting light between 430 and 1200 nm was used. Adapalene 0.1% in gel form was used. One side of the face was treated with plain adapalene gel and another side with a combination of daily application of adapalene, with fortnightly exposure of IPL. A total of four sittings of IPL at the interval of 15 days were given. Final evaluation was done 2 weeks after the last session of IPL. Results: On adapalene + IPL-treated side, statistically significant reduction in comedones started from the 2nd visit,P < 0.05. On the 6th visit, there was statistically significant difference in mean comedones (P < 0.05) between two sides. After the study (9 weeks), the mean reduction in inflammatory lesion was 69.98% for adapalene-treated side and 79.92% for combination therapy. Conclusion: IPL therapy with 430–1200 nm wavelength filter is an effective adjuvant therapy when used with adapalene 0.1 gel. It gives an additional benefit in the treatment of acne. We can avoid systemic antibiotics and retinoids using adapalene and IPL combination in mild-to-moderate acne.



How to cite this article:
Karan S, Vikrant J, Anil G. A comparative study between topical adapalene (0.1%) versus a combination of topical adapalene (0.1%) and intense pulsed light therapy in the treatment of inflammatory and noninflammatory facial acne vulgaris: A split-face randomized controlled trial.Indian J Drugs Dermatol 2019;5:19-25


How to cite this URL:
Karan S, Vikrant J, Anil G. A comparative study between topical adapalene (0.1%) versus a combination of topical adapalene (0.1%) and intense pulsed light therapy in the treatment of inflammatory and noninflammatory facial acne vulgaris: A split-face randomized controlled trial. Indian J Drugs Dermatol [serial online] 2019 [cited 2019 Oct 17 ];5:19-25
Available from: http://www.ijdd.in/text.asp?2019/5/1/19/263093


Full Text



 Introduction



Acne vulgaris is one of the most common dermatological disorders encountered in clinical practice. Although it is not a life-threatening disorder, it usually disfigures the face during the vulnerable adolescent period. It predominantly affects sites that cannot be hidden. It intensifies the teenager's instability and often leaves permanent scars on the psyche.

The incidence of acne vulgaris is so common that one can call it as a physiological process, but it is better regarded as a disease because it has an inflammatory component which produces significant disfigurement on the face which is cosmetically and socially a very important site.[1] The pathogenesis of acne is multifactorial, including hormonal, microbiological, and immunological mechanisms. It is a disease of pilosebaceous follicles causing excess sebum production and proliferation of Propionibacterium acnes. Several factors affect disease severity and its sequele.

Clinical presentation of the disease consists of comedones, papules, pustules, and nodules following which residual scarring and pigmentation may occur on the affected sites. It is challenging for a dermatologist to treat acne and prevent its sequelae. Various treatment modalities are available for acne. Conventionally, topical medicines and systemic drugs form the first line of treatment. Lasers and light-based therapies are also gaining popularity nowadays with good clinical results. The choice of treatment depends on the type and severity of the disorder.

Most topical and oral treatments for acne are inconvenient and have side effects. Adapalene, third-generation retinoid, was developed as a topical treatment for acne and has demonstrated good clinical efficacy. If used with full compliance, adapalene has a better benefit–risk ratio than other retinoids.[2]

Lights and lasers have received immense attention in the management of acne in the past 10 years. There is rising number of lasers and light-based therapies for the treatment of acne. These therapies have been reported to be convenient, safe, and effective in treating acne. Patients have better compliance for these therapies as these are noninvasive and give results in shorter duration.[3] Among these therapies, intense pulsed light (IPL) therapy has been proven to be useful in reducing inflammatory lesions of acne.[4]

Both adapalene and IPL therapy used as monotherapy have been proven to be effective in treating inflammatory lesions of acne. There is a paucity of reports mentioning the use of IPL as adjuvant therapy. Hence, we intend to compare the outcome when IPL is used as an adjuvant therapy with adapalene.

Aims and objectives

To evaluate the efficacy and safety of topical adapalene (0.1%) in facial acne vulgarisTo evaluate the efficacy and safety of topical adapalene in combination with IPL in facial acne vulgarisTo compare the above results.

 Materials and Methods



The present study was carried out in the department of dermatology of a tertiary health care institute. We performed a prospective, parallel group, randomized controlled trial. Considering type I error (alpha) as 0.05, power as 80%, and an expected difference of 30% in response rate between the groups, the sample size was calculated as 30 in each group.

We included 50 patients in this study, considering the future rate of dropout. Using random allocation software for parallel group randomized trials, one side of the face was randomly selected and treated with topical adapalene gel, while the other side of the same patient was treated with a combination of IPL and topical adapalene gel. This study was approved by our institute's ethics committee of Dr. Vasantrao Pawar Medical College, Nashik, with registration number IEC/58/09. Written informed consent of each patient was taken from the patient before enrolling.

One investigator (KS) enrolled the patients, second investigator (VJ) administered the treatment, and follow-up evaluation was done by a third investigator (AG). The final evaluator and statistician were blinded in the study. Blinding of the patient and investigator administering IPL were not possible in this split-face study.

Patient selection

Inclusion criteria

Patients with bilateral involvement of face and having minimum 10 inflammatory and/or noninflammatory acne lesions on each side, including comedones, papules, and pustules; patients above 18 years of age; and patients not on any antiacne medication for the last 1 month were included.

Exclusion criteria

Pregnant and nursing women; any woman of childbearing potential who is not ready to use contraception as advised; patients receiving any systemic steroid or retinoids for the last 1 month; patients with other forms of acne (e.g., acne fulminans, acne conglobata, and nodulocystic acne); patients with a history of photosensitive disorder or history of photosensitive medication; and patients with known hypersensitivity to adapalene or light-based therapies were excluded.

Treatment modalities

An IPL device equipped with an acne treatment filter which emits light between 430 and 1200 nm was used. Adapalene 0.1% in gel form was used.

Methods

On visit 1 (day 1), all selected patients were evaluated for baseline lesion count, degree of erythema, clinical grading, and Michaelson severity index (MSI) score.[5]

Except for clinical grading, all other parameters were recorded separately for each side of the face.

Lesion count

Lesion count was done by the same investigator on every visit. Microcomedones were not counted. Open and closed comedones were counted together. All inflamed lesions, i.e., lesions with erythema, were considered as papules, and visible pus-filled lesions were counted as pustules. Nodules, cysts, and infiltrated lesions were excluded.

Based on this, the MSI was calculated. According to this MSI,[5] multiplication factors for individual types of acne lesions were assigned. Multiplication factor was 0.5 for comedones (open and/or closed), 1.0 for papules, and 2.0 for pustule. Taking “n” as the number of lesions, the severity index was calculated as follows: MSI = (0.5 × n) + (1 × n) + (2 × n).

Erythema

Grading of erythema was done as follows: no erythema; mild – just perceptible erythema (pink colored); moderate – red colored; severe – fiery or dark red erythema.

All patients received test shots of IPL on their first visit. Test shots of IPL were given on postauricular area. Patients were instructed to use adapalene 0.1% gel on their whole face once at night throughout the treatment period. After IPL session, the patients were instructed not to apply adapalene gel for two nights.

On visit 2 (after 1 week), if no untoward event occurred to the test shots, then as per randomization patient's one side of the face was treated with IPL therapy using an acne treatment filter (430–1200 nm wavelength).

The parameters of IPL therapy were adjusted according to Fitzpatrick's skin type and previous response to treatment. Total fluence used was depending on patient's skin type and its response to previous treatments. For the test shot, 5 and 10 J/cm2 were used. Treatment fluence was in between 15 and 20 J/cm2. Total number of shots required to cover one side of the face was around 10–12. Other parameters which were kept constant are first pulse width – 10 ms, first pulse duration – 2.5 ms, subsequent pulse width – 10 ms, subsequent pulse duration – 2.5 ms, number of pulses – 2.

Immediately after applying a cooling gel on treatment area (about 1-mm thickness), the handpiece was kept and the button was pressed to emit the light. After a gap of 2–3 s, subsequent areas were treated in the same manner without overlapping. Little heat or stinging sensation was considered as an effective shot. During the procedure, both patient and physician used UV protective goggles to protect the eyes. Sun protection was mandatory for all patients during the treatment period. Any adverse reaction to light therapy was noted. The patients were called after 2 weeks for the next sitting of IPL.

On visits 3–5 (after weeks 3, 5, 7, respectively), the same procedure was repeated as of visit 2. On each visit, detailed evaluation of lesion count and its severity was done. Total four sessions of IPL were done at the interval of 2 weeks.

On visit 6 (after week 9), final evaluation of patients' lesion count and severity scoring of both side were done.

Statistical analysis

Data were collected and statistically evaluated using “z” test to compare the results. The “z” test was performed using the Statistical Package for the Social Sciences (SPSS inc. Chicago, IL, U.S.A) for Windows, version 17.0 software, for 50 participants in each group. A P < 0.05 was considered as statistically significant.

 Results



[Table 1] shows baseline demographics. [Table 2] shows the mean values of comedones on each visit and percentage reduction in number of comedones on each visit with topical adapalene.{Table 1}{Table 2}

[Table 3] shows the mean values of comedones on each visit and percentage reduction in number of comedones on each visit with combination of topical adapalene and intense pulsed light.{Table 3}

[Table 4] shows the mean values of inflammatory lesions on the right side of face and percentage reduction in number of inflammatory lesions during each visit.{Table 4}

[Table 5] shows the mean values of inflammatory lesions on the left side of face and percentage reduction in number of inflammatory lesions during each visit.{Table 5}

[Table 6] shows the mean values of MSI score on the right side of face and % reduction in MSI score during each visit.{Table 6}

[Table 7] shows the mean values of MSI scores on the left side of face and percentage reduction in MSI score during each visit.{Table 7}

[Table 8] shows the percentage reduction in MSI score during each visit with (visit 1-3).{Table 8}

[Table 9] shows the percentage reduction in MSI score during each visit (visit 4-6).{Table 9}

[Table 10] shows side effects with adapalene and IPL.{Table 10}

 Discussion



Acne is a disease that affects almost 90% of the population. The clinical presentation ranges from comedones to red papules, pustules, and nodules. Scarring is associated, which can be extremely disfiguring. The disease is associated with higher incidence of depression, social deprivation, and low self-esteem.

IPL devices use flash lamps and band passed filters to emit polychromatic incoherent high-intensity pulsed light of determined wavelength and pulse duration. Basic principle of IPL is selective thermal damage of the target tissue as in that of the laser.

In acne, IPL has following effects:[6]

Photodynamic effect is evoked by visible and UV light that is absorbed by porphyrins (protoporphyrin IX, coproporphyrins III) that are produced by P. acnes. It is followed by generation of reactive oxygen species which have bactericidal effects. These porphyrins have absorption peaks at 400, 510, 542, 578, 630, and 665 nmSelective photothermolysis of smaller blood vessels supplying sebaceous glands which reduce sebum production. Hb has an absorption peak at 580 nm.

The use of IPL offers the possibility to cover the absorption peaks of both Hb and porphyrins; hence, it is a suitable tool for acne treatment.

In the present study, we compared the efficacy of IPL as an adjuvant therapy when used with topical adapalene. We used only adapalene 0.1% gel for the treatment of inflammatory and noninflammatory lesions in acne vulgaris patients on one side of the face. We found a significant decrease in the inflammatory (papules + pustules) and noninflammatory lesions (comedones) from the baseline. At the completion of the study (at 9 weeks), the total comedone reduction was 56.60% and that of inflammatory lesion was 69.98% [Figure 1], [Figure 2], [Figure 3], [Figure 4]. The reduction in the mean MSI score in patients was 65.54% at the completion of the study. The significant reduction in mean of inflammatory lesions, noninflammatory lesion, and total lesion counts started from the 1st week onward. Our results are similar to that of Rao et al.,[7] who found significant decrease (P < 0.05) in mean inflammatory and noninflammatory lesion and total lesion counts from the 1st week onward. At 12 weeks, total reduction was 66.7% for inflammatory lesions and 70.3% for open and around 50% for closed comedones. Decrease in total lesion count was 69% at 12 weeks. Percy[8] also found a significant reduction in the total number of lesions using adapalene 0.1% gel. Of patients who completed 12 weeks of therapy, 96.3% showed a global improvement in their acne from baseline. Eighteen percent showed complete clearing of lesions and another 44% showed a significant improvement (>75%).{Figure 1}{Figure 2}{Figure 3}{Figure 4}

Behrooz et al.[9] and Sami et al.[10] found a significant decrease in total lesion count using IPL therapy. Sami et al. mentioned clearance of 90% of lesions after 6 sessions (one treatment per week). Kumaresan and Srinivas[11] also found 49.19% reduction in mean total MSI score after four sessions of IPL alone. Rojanamatin and Choawawanich[12] used 5-aminolevulinic acid in combination with IPL, who found a significant decrease in the total lesion count. Chang et al.[13] compared efficacy of combination of IPL and benzoyl peroxide with benzoyl peroxide alone. They found no additional benefit of IPL in reducing inflammatory lesions.

We used combination of adapalene 0.1% gel and IPL in the treatment of acne vulgaris on one side of the face after randomization. At the completion of the study (9 weeks), the reduction in inflammatory and noninflammatory lesion was 79.92% and 64.37%, respectively. The reduction in MSI score in patients was found to be significant as compared to baseline. The reduction was 73.94% at the completion of the study (at 9 weeks).

When both treatment modalities were compared, we found a significant reduction in lesion count (both inflammatory and noninflammatory) and MSI score, using adapalene alone and combination therapy.

The additional significant benefit of IPL was observed from the 7th week when compared to adapalene alone in reducing lesion count. The mean reduction in comedone was 56.6% for adapalene treated side and 64.37% for IPL-treated side at the completion of the study (9 weeks) and mean reduction in inflammatory lesion was 69.98% for adapalene-treated side and 79.92% for combination therapy at the completion of the study (9 weeks).

The difference in the mean reduction of MSI was significant from the 7th week between adapalene-treated side and IPL-treated side. At the completion of the study (9 weeks), the mean reduction in MSI was 65.54% and 73.94% for adapalene-treated side and adapalene + IPL-treated side, respectively. This difference in the reduction of mean MSI was found to be highly significant (P < 0.01). No study of comparison of adapalene gel and combination of IPL with adapalene gel in acne was available, so we compare our results with Chang et al.[13] These results are not consistent with that of Chang et al.,[13] who found no additional benefit of IPL over benzoyl peroxide alone. They used 3-week interval between IPL sittings and number of treatment sessions was 3, whereas we used four sittings of IPL at 2 weeks' interval. This might be the responsible factor for the difference.

Side effects

In our study, the side effects observed were burning, dryness, and erythema. Of these, the most common side effects observed on adapalene-treated side were burning which was accounted in 46% of patients, followed by dryness in 8% patients and erythema in 2% patients. On IPL-treated side, burning (30%) was predominant side effect, followed by erythema (18%). All these side effects were transient and subsided within 5–7 days. In a study by Rao et al.,[7] few patients discontinued the therapy due to severe side effects. In our study, all side effects were mild to moderate and none of the subjects discontinued the therapy. Our findings of side effects are similar to Percy,[8] who also noted burning, dryness and erythema as common side effects. Cunliffe et al.[14] and Dunlap et al.[15] compared adapalene 0.1% gel with tretinoin 0.025% cream and found adapalene to be superior to tretinoin in terms of tolerability.

Erythema was observed mainly on IPL-treated side after two sitting of IPL, which was temporary, subsided within 2 days. Sami et al.[10] experienced minimal adverse events as being mild and usually self-limiting.

 Conclusion



Adapalene 0.1% gel is an effective treatment modality for the treatment of inflammatory and noninflammatory lesions of acne. The drug is safe and has minimal side effects such as burning and dryness.

IPL therapy with 430–1200 nm wavelength filter is an effective adjuvant therapy when used with adapalene gel. This light therapy is well tolerated by patients and has minimal side effects, which are transient.

Compared to adapalene as monotherapy, combination therapy (adapalene + IPL) does have an additional benefit in the treatment of acne. It causes faster clearance of lesions. We recommend four or more sittings at 2 weeks' interval to achieve additional benefit. IPL therapy also has an effect on acne sequel such as pigmentation. If we use this combination of adapalene and IPL, we can treat mild-to-moderate acne without use of systemic antibiotics and isotretinoin, avoiding side effects of these drugs. This combination gives advantage of treating acne sequelae such as pigmentation.

There are no sufficient studies mentioning the role of IPL as an adjuvant therapy; hence, more studies are invited to prove the effectiveness of IPL on the long term.

Limitations

The limitations of the study were (a) a small sample size, (b) short follow-up period, and (c) blinding of patient and IPL operator was not possible.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest

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