Comparison of Fractional CO2 Laser Monotherapy and Its Combination With Either Topical Vitamin C or Topical Timolol in the Treatment of Post-Acne Erythema: A Split Face Study

Background:

Acne vulgaris is one of the most prevalent causes of the clinic visit among young adults. Post-acne erythema (PAE) is one of the major sequelae of acne vulgaris and it commonly persists for long times as several months. It can be a predictor of developing atrophic scars in predisposed people. It almost develops in individuals with light skin phototypes. Although the exact mechanism of PAE is unknown, it is thought to occur secondary to epidermal thinning with resultant telengectasia and dermal vascular dilatation changes in response to the healing process. Other explanation is that PAE results from external agents as topical therapy which may cause irritation. Searching the literature, different results were found yet no gold standard treatment for PAE could be found till now. A very novel review categorized treatment of PAE into light and laser therapies which included; alexanderite (Alex) laser, pro-yellow laser, erbium glass fractional laser, Q-switched Neodymium:yttrium aluminum-garnet (Nd:YAG) laser pulsed dye laser, high power optically pumped semiconductor laser (HOPSL), broad band treatment, intense pulsed light (IPL) therapy, and radiofrequency (both fractional microneedling, and invasive short pulsed-type bipolar radiofrequency device (IPBRF)), they were all found to be effective modalities. The other modalities mentioned with also favorable outcome and more affordability were topical therapies including; 1.5% Oxymetazoline (OXZ), 5% tranexamic acid, vitamin C gel, brimonidine tartarate 0.2%, and a topical complex containing Glyceryl-octyl-ascorbic acid (GOVC), ascorbyl 2-phosphate 6-palmitate (APP), and DL-a- tocopherol phosphate (TP). Moreover topical timolol was found recently to be an effective option for PAE treatment. Fractional Co2 laser role in post acne erythema scars wasn't found in the literature; yet a study by Park et al, illustrated the role of fractional potothermolysis of 1550 nm, erbium-doped laser in PAE by many theories including; targeting tissue water which is a major component of blood vessels, it also results in photothermal damage of dermal vasculature leading to improved erythema. In addition, it produces multitudes of dermal microthermal zones of injury that may lead to multiple, random targeting of the dermal blood vessels. Although pulsed dye laser (PDL) targets hemoglobin, the fact that fractional laser penetrates deeper adds a more benefit for the more deeply located vessels in the dermis. Vitamin C (Vit. C) is a known potent antioxidant. A limited amount of vit. C is absorbed regardless the oral dose, due to its active transport. Moreover, vit. C bioavailability in the skin is insufficient with its oral intake, so its topical preparations are preferred in dermatological uses. It is used in numerous dermatological purposes including; photodamage, hyperpigmentation, and rejuvenation. A Japanese study was done using Isostearyl-L-ascorbic acid (ISAA) for treatment of post acne erythema, and post inflammatory hyperpigmentation and found significant improvement. They attributed this role to wound healing promoting effects of vitamin C through proliferation of collagen synthesis and inhibition of matrix metalloproteinase (MMP), and inhibition of tyrosinase. Besides, Vitamin C has anti-inflammatory effects by inhibiting pro-inflammatory cytokines including; IL1β, and TNF-α. Another study was done combining Vit.C with tranexemic acid and microneedling has found significant decrease in post acne erythema scars in comparison with microneedling alone.

Timolol, is a well tolerated nonselective β-adrenergic receptor blocker, its use becomes obviously increasing nowadays in a lot of dermatological purposes such as; infantile hemangioma, wound healing, Kaposi sarcoma, pyogenic granuloma. Moreover, it was reported recently to be effective in PAE treatment by inducing vasoconstriction, and inhibiting neoangiogenesis, this is deduced from its known role in treatment of infantile hemangioma. Taken together, and to the best of our knowledge, the literature lacks gold standard treatment for post acne erythema management, and no studies were found to compare effects of combined fractional CO2 laser with timolol Vs, fractional Co2 laser combined with Vit. C, Vs, fractional Co2 alone in patients of post acne erythema, which necessitates to be evaluated, to reach a better consensus while dealing with such common sequel.

Objectives:

• Assessment of efficacy of fractional laser in post acne erythema. - Assessment of topical vitamin C combined with fractional laser in treatment of post acne erythema. - Assessment of topical timolol combined with fractional laser in treatment of post acne erythema. - Comparison between efficacy of fractional Co2 laser combined with topical vitamin C Versus, fractional Co2 laser with topical timolol Versus, fractional Co2 laser alone in patients with post acne erythema.

Study design:

Randomized controlled trial

Study Methods

• Population of study: Patients with post acne erythema from outpatient dermatology department clinic, Kasr Alainy.
• Forty (40) Patients -with persistent post acne erythema for one month after acne vulgaris resolution or more- from outpatient dermatology department clinic, Kasr Alainy will be collected and written informed consent will be taken.
• Twenty patients(20) will undergo a split face study, with half face application of fractional Co2 session with the following parameters( power:15J, Dual time: 700, spacing:500, stack:1) followed by topical Vitamin C, the other half will undergo a fractional Co2 session alone. The other twenty patients (20) will undergo a split face study as well, with half face application of fractional Co2 session with the following parameters( power:15J, Dual time: 700, spacing:500, stack:1) followed by topical timolol 0.5% drops, the other half will undergo a fractional Co2 session alone.
• Laser sessions will be done every month for three months, and topical treatment will be continued in the intervals between sessions.
• Evaluation of patients will be done by dermoscopy, spectrophotometry, photography, and clinician erythema assessment scale (CEAS).
• Randomization will be carried out by asking patients who fulfill the inclusion criteria to draw closed opaque envelopes to determine to which group they will be assigned.
• Patients will be followed for three months after the treatment duration.

Statistical analysis • The collected data will be coded, entered, presented, and analyzed by computer using a database software program, Statistical Package for Social Science (SPSS) version.

• Qualitative data will be represented as frequencies and percent and Chi square (X2) test was used to detect relation between different qualitative variables.
• For quantitative variables mean ± standard deviation (SD) and median with range (for not normally distributed data) will be computed and Independent t-test (t) will be used for detection of difference between different quantitative variables, while nonparametric data will be evaluated with Mann-Whitney U test. funding: Vichy will fund us with topical Vitamin C 15%