Efficacy of oral isotretinoin in combination with levocetirizine in management of severe acne vulgaris

Nội dung text: Efficacy of oral isotretinoin in combination with levocetirizine in management of severe acne vulgaris

1. SCIENTIFIC RESEARCH EFFICACY OF ORAL ISOTRETINOIN IN COMBINATION WITH LEVOCETIRIZINE IN MANAGEMENT OF SEVERE ACNE VULGARIS Thai Thi Dieu Van*, Nguyen Van Thuong*,**, Truong Thi Huyen Trang**, Vu Thai Ha*,**, Vu Thi Hong Luyen**, Vu Thanh Tung**, Hoang Van Tam*,**, Dinh Huu Nghi*,**, Vu Huy Luong*,**. ABSTRACT Objective: To evaluate the outcomes of the treatment of severe acne vulgaris by combining oral isotretinoin and levocetirizine. Method: controlled comparative clinical trial. 60 patients with severe acne vulgaris were randomly divided into 2 groups: 30 patients in treated group were managed with oral isotretinoin 0,3 - 0.5mg/kg/ day and levocetirizine 5mg/day and 30 patients in control group were managed with oral isotretinoin 0,3 - 0.5mg/kg/day only. Assessment was made at baseline, after 3, 4, 8 and 12 weeks. Result: at week 12, the treated group showed better outcome compared with control group: 46.7% had good improvement, 53.3% had moderate improvement and 0% had little improvement, meanwhile in control group the rates were 10%, 83.3% and 6.7%, respectively (p < 0.05). Side effects including pruritus, tingling in treated group were lower than control group (p < 0.05). Quality of life in both groups were improved but better improvement was achieved in treated group (p < 0.05). Conclusion: oral isotretinoin combined with levocetirizine showed better outcomes, less side effects and better improved quality of life than oral isotretinoin only in management of severe acne vulgaris. Keywords: acne vulgaris, severe, isotretinoin, levocetirizine, antihistamine. 1. INTRODUCTION therapeutics which can improve patients’ quality Acne is a chronic condition of pilosebaceous of life [2], [3]. unit, commonly affects adolescents [1]. Although The efficacy of isotretinoin in management of this is a self - limited disease but its complications acne has been demonstrated in many studies. It is including atrophic scarrings, keloids can be life - the only drug which targets all causative factors of long and become psychological burdens which acne. However, isotretinoin has many side effects, cause low self - esteem, depression and anxiety. As commonly cheilitis, xerosis, erythema and pruritus. a result, there is a significant demand for effective These symptoms often disappear after 1 - 2 Scientific Reviewer: PhD. Pham Thi Minh Phuong months but they affect significantly on the patients’ * Hanoi Medical University adherence so it is important to use adjuvant ** National hospital of Dermatology and Venereology therapies to limit these disadvantages [4], [5]. 60 DERMATOLOGY No. 29 (September 2019)
2. SCIENTIFIC RESEARCH The roles of antihistamines in allergic ramdomly into 2 groups, each group had 30 condition have been well - established. Recently, patients. researchers have demonstrated efficacy of - Treatment: antihistamines especially the second generation Treated group: oral isotretinoin 0,3 - 0.5mg/ in reducing seborrhae, improving acne and kg/day combined with levocetirizin 5mg/day, reducing side effects of isotretinoin [3], [6], [7]. facial wash by Ziaja Med Physioderm in the For these reasons, we conducted this clinical morning and evening, topical acid azelaic 20% 2 trial to evaluate efficacy of levocetirizine in times/day after washing in 12 weeks. combination with isotretinoin in managing Control group: oral isotretinoin 0,3 - 0.5mg/ severe acne vulgaris. kg/day only, facial wash by Ziaja Med Physioderm 2. METHOD in the morning and evening, topical acid azelaic 20% 2 times/day after washing in 12 weeks. 2.1. Objects - Assessment: 60 severe acne vulgaris patients according to + Week 0: Doctor examines, counts number Global acne grading system (GAGS), ≥ 18 years - of lesions, evaluates GAGS and Dermatology life old, treated in National hospital of Dermatology quality index (DLQI). and Venereology from August 2018 to July 2019. • GAGS is a quantitative scoring system to 2.2. Method assess acne severity. The total severity score is derived from summation of 6 regional sub scores. Controlled comparative clinical trial on 60 severe acne vulgaris patients. They were assigned Chest and Regions Forehead Right cheek Left cheek Nose Chin back Score (A) 2 2 2 1 1 3 Score (B) No lesions: 0 Comedones: 1 Papules: 2 Pustules: 3 Nodules: 4 Score A x Score B Total Mild ( 1 - 18), Moderate (19 - 30), Severe (31 - 38), Very severe (> 38) No. 29 (September 2019) DERMATOLOGY 61
3. SCIENTIFIC RESEARCH • DLQI is a ten – question questionnaire used + Moderate improvement: reduced from ≥ to measure the impact of skin disease on the 50 to < 80% number of lesions. quality of life. + Little improvement: reduced from ≥ 25 to < + Week 3, 4, 8, 12: Doctor examines, counts number 50% number of lesions. of lesions, evaluates GAGS, DLQI and side effects. + No improvement: reduced < 25% number - Outcome assessment: of lesions. + Good improvement: reduced ≥ 80% number of lesions. 3. RESULTS 3.1. Demographic and baseline characteristics Treated group Control group p Male 19 19 Sex 1 Female 11 11 Age (year) 22,3 ± 4.0 22,4 ± 4.2 0.93 Duration (year) 2,2 ± 1.2 2,3 ± 1.0 0.81 Weight (kg) 56,1 ± 7.0 55,2 ± 6.8 0.61 BMI 20,3 ± 2 20,4 ± 1.9 0.94 Number of inflammatory lesions 44,3 ± 10.9 46,1 ± 10.4 0.51 Number of non - inflammatory lesions 21,6 ± 16.9 20,0 ± 14.6 0.69 Total lesions 65,9 ± 19.2 66,1 ± 18.2 0.97 GAGS 32,6 ± 2.6 32,9 ± 1.6 0.64 DLQI 15,7 ± 4.7 16,3 ±4.3 0.59 At baseline, regarding sex, age, duration, weight, BMI, number of lesions, GAGS score and DLQI in both groups had no significant difference (p > 0.05). 3.2. Treatment outcomes 3.2.1. Inflammatory lesions counts Treated group had less inflammatory lesions at week 3, week 4, week 8 and week 12 than control group, difference showed statistical significance at week 12 (p < 0.05). 62 DERMATOLOGY No. 29 (September 2019)
4. SCIENTIFIC RESEARCH Inflammatory lesion counts 50 45 40 35 30 25 20 15 10 5 0 Week 0 Week 3 Week 4 Week 8 Week 12 Treated group Control group 3.2.2. Non - inflammatory lesion counts Non inflammatory lesion counts 25 20 15 10 5 0 Week 0 Week 3 Week 4 Week 8 Week 12 Treated group Control group Number of non - inflammatory lesions in both groups at week 3, 4, 8 and 12 showed no statistical difference (p > 0.05). No. 29 (September 2019) DERMATOLOGY 63
5. SCIENTIFIC RESEARCH 3.2.3. Total lesions counts Total lesions counts 80 70 60 50 40 30 20 10 0 Week 0 Week 3 Week 4 Week 8 Week 12 Treated group Control group Treated group had less total lesions at week 3, week 4, week 8 and week 12 than control group, difference showed statistical significance at week 12 (p < 0.05). 3.2.4. Changes in GAGS score Changes in GAGS score 35 30 25 20 15 10 5 0 Week 0 Week 3 Week 4 Week 8 Week 12 Treated group Control group Treated group had greater reduction in GAGS score than control group at week 0, week 3, week 4, week 8 and week 12. Difference showed statistical significance at week 12 (p < 0.05). 64 DERMATOLOGY No. 29 (September 2019)
6. SCIENTIFIC RESEARCH 3.2.4. Outcome assessment Good Moderate Little No p improvement improvemnt improvement improvement n 14 16 0 0 Treated group % 46.7 53.3 0 0 0,002 n 3 25 2 0 Control group % 10 83.3 6.7 0 Treated group was more effective than control group, difference showed statistical significance with p < 0.05. 3.2.5. Side - effects assessment - Acne flares 5 patients (16.7%) in treated group and 8 patients in control group (26.7%) experienced acne flares, mainly at week 3 and week 4. - Other side - effects. Week 3 Week 4 Week 8 Week 12 Side - Treated Control Treated Control Treated Control Treated Control effects group group group group group group group group Cheilitis n 23 27 18 24 10 14 4 3 % 76.7 90 60 80 33.3 46.7 13.3 10 p 0.2 0.09 0.3 1 Xerosis n 9 11 9 8 3 3 1 0 % 30 36.7 30 26.7 10 10 3.3 0 p 0.6 0.8 1 1 Dry eyes n 3 5 3 2 0 0 0 0 % 10 16.7 10 6.7 0 0 0 0 p 0.7 1 Xerostomia n 3 0 2 0 0 0 0 0 % 10 0 6.7 0 0 0 0 0 p 0.2 0.5 Epistaxis n 0 0 0 0 0 0 0 0 % 0 0 0 0 0 0 0 0 p Pruritus, n 10 19 5 13 0 4 0 1 tingling % 33.3 63.3 16.7 43.3 0 13.3 0 3.3 p 0.02 0.02 0.04 1 No. 29 (September 2019) DERMATOLOGY 65
7. SCIENTIFIC RESEARCH Cheilitis was the most common side - effect, affecting 76.7% patients in treated group and 90% in control group at week 3, followed by pruritus and xerosis. No patient experienced epistaxis. Side - effects including cheilitis, xerosis, xerostomia, epistaxis were not different between 2 groups (p > 0.05) except for pruritus which had significant difference with p < 0.05 at week 3, 4, 8. 3.2.6. DLQI changes DLQI changes 18 16 14 12 10 8 6 4 2 0 Week 0 Week 4 Week 8 Week 12 Treated group Control group Quality of life of patients in treated group was better than in control group as DLQI reduced more significantly, with p < 0.05 at week 8 and week 12. 4. DISCUSSION adjuvant therapy when applying low dose or Indication of isotretinoin is to treat moderate intermittent dose [8], [9] to severe acne vulgaris which does not respond In our study, after 12 weeks, number of to other conventional therapy. This is the only inflammatory lesions in isotretinoin combined drug which can target all the causative factors with levocetirizine group reduced more of acne however dose - dependant side - effects significantly than using isotretinoin only impact significantly on patients’ adherence. To (p < 0.05). However, the number of non - inflammatory overcome these disadvantages, many authors lesions in both groups were not different (p > 0.05). suggested using lower dose than recommended As a result, GAGS in treated group reduced more dose in guidelines (0.5 - 1.0 mg/kg/day) but significantly than in control group (11.0± 5,2 at week the efficacy of low – dose or intermittent dose 12 compared with 14.0 ± 5.0). of isotretinoin in acne is still limited and lack Histological and immunological studies of evidences. As a result, it is necessary to add demonstrated that inflammation was the 66 DERMATOLOGY No. 29 (September 2019)
8. SCIENTIFIC RESEARCH fundamental process in the early development > 0.05) except for pruritus and tingling which had of acne lesions [10]. Inflammatory reaction was significant difference with p < 0.05 at week 3, 4, mediated by histamine, leukotriene and moreover, 8. This result was similar to Duong Thi Lan (2018) C. acnes changed pH of micro - environment in and Yosef (2016) and could be explained by anti - pilosebaceous unit, formed an optimal condition pruritus effect of antihistamin levocetirizine [6], [13]. to generate histamine and other inflammatory Acne, especially severe acne can impact mediators which caused pruritus. Levocetirizin seriously on patients’ mental health. Successful not only inhibited H1 - receptors but also had treatment leads to reduction of depression, other anti - inflammatory effects which had been anxiety, low self - esteem but some well - proved in many in vitro and in vivo studies [11]. known adverse effects of isotretinoin including Beside, Pell et al has shown that antihistamine depression and suicide can worsen the mental can reduce squalene level in seborrheic gland, problems of patients. In our study along with squalene is an oxydized substance, secreted lesions reduction, GAGS reduction, reduction in from sebocytes and plays a role in comedonal pruritus, pain, the quality of life of patients also and inflammatory pathogenesis. He also found improved in both groups. However DLQI in treated histamine receptor presence on sebocytes, group was lower than control group with p < 0.05 demonstated how an antagonist to these from week 4 which implicated that the quality receptors modulated cellular function [12] of life in treated group was better improved . [13]. So levocetirizine took effect through this Further study was necessary to evaluate whether mechanism, however, our study limitation was it was because of combination of isotretinoin not using seborrheic measuring equipment to and levocetirizine improved acne better and evaluate seborrhare in patients. lesser side effects which made the patients more Through many demonstrated evidence, comfortable or levocetirizine reduced mental the treated group combined isotretinoin side – effect of patients. with levocetirizine had 46.7% achieved good 5. CONCLUSION improvement, 53.3% moderate improvement and 0% little improvement, in control group was Oral isotretinoin combined with levocetirizine 10%, 83.3% and 6.7% respectively. The treated showed better outcomes, less side effects and group showed better efficacy than control group, better improved quality of life than oral isotretinoin difference had statistical significance with p < 0.05. only in management of severe acne vulgaris. Side - effect assessment REFERENCES Acne flares: 16.7% in treated group and 26.7% in control group experienced acne flares, all in 1. Hay R.J., Johns N.E., Williams H.C., et al. mild level, mainly at week 3 and week 4. Side - (2014). The global burden of skin disease in 2010: effects including cheilitis, xerosis, xerostomia, an analysis of the prevalence and impact of skin epistaxis were not different between 2 groups (p conditions. J Invest Dermatol, 134(6), 1527-1534. No. 29 (September 2019) DERMATOLOGY 67
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