Intradermal in The Professional Medical Journal www.theprofesional.com ORIGINAL PROF-0-4190 https://doi.org/10.29309/TPMJ/2021.28.03.4190

Evaluate the efficacy of intradermal tranexamic acid in melasma. 1. MBBS, FCPS Assistant Professor Dermatology Dow University of Health Sciences, Karachi. 2. MBBS, FCPS Associate Professor Dermatology Tayyaba Iqbal1, Sadaf Ahmed Asim2, Madiha Sajid3, Sadia Hafeez4, Maria Mansoor5, Reema Mirza6 Dow University of Health Sciences, Karachi. ABSTRACT… Objective: To evaluate the efficacy of intradermal tranexamic acid in melasma. 3. MBBS, FCPS Stduy Design: Cross-Sectional study. Setting: Out-patient Department of Dermatology at Assistant Professor Dermatology Dow University of Health Sciences, Dow University of Health Sciences. Period: January 2018 to June 2018. Material & Methods: Karachi. Enrolling 73 patients the research was done on patients with resistant melasma. For this 0.2 4. MBBS, FCPS ml tranexamic acid diluted in 0.8 ml normal saline was injected intradermally into the melasma Assistant Professor Dermatology lesion at 1 cm distance at every 2 weeks for 4 months and results were analysed by using the Dow University of Health Sciences, Karachi. modified Melasma Area and Severity Index (MASI) at their first visit and then monthly with strict 5. MBBS, FCPS sun protection. A total of 73 patients were included in this study with age ranging from 22 years Assistant Professor Dermatology to 47 years. All of them had resistant melasma and had not taken any treatment for the last six Dow University of Health Sciences, Karachi. months. Results: Out of 73 patient 10 (13.7%) patients had poor response, 48 (65.8%) patients 6. MBBS, FCPS had fair response, 14 (19.1%) patients had good responses and only 1 (1.4%) had excellent Assistant Professor Dermatology response. No significant side effects were observed. Out of 73 patients, 63 patients were Dow University of Health Sciences, satisfied with the treatment. Only 2 patients complained of redness over the affected area which Karachi. subsided within a week without any intervention, no other side effects were noted. Conclusion: Correspondence Address: Intralesonal tranexamic acid is safe, effective and an affordable option in resistant melasma. Dr. Tayyaba Iqbal Departement of Dermatology Melasma, MASI, Tranexamic Acid. Dow University of Health Sciences, Key words: Karachi. [email protected] Article Citation: Iqbal T, Asim SA, Sajid M, Hafeez S, Mansoor M, Mirza R. Evaluate the Article received on: efficacy of intradermal tranexamic acid in melasma. Professional MedJ 23/09/2019 2021; 28(3):350-354. https://doi.org/10.29309/TPMJ/2021.28.03.4190 Accepted for publication: 08/07/2020 INTRODUCTION , while only 20% of melasma occurred Melasma is the most prevalent and distressing before the pregnancy. The main risk of onset pigmentary disorder among Asians women during pregnancy was the hormonal cause and mainly in their reproductive years, but 10% associated with increased sun exposure.4,5 involvement is also observed in men.1 It is a most frequent acquired hypermelanosis, which There are three clincal patterns of melasma affects sun-exposed areas of the skin. Sun according to their localization: a centrofacial exposure, pregnancy, hormonal treatment and pattern, a malar pattern, and a mandibular endorcinogical disorders are the most common pattern. Melasma can also be classified on the aggrevating and precipiatating factors.2 Melasma basis of localization of melanosomes either in frequently causes a considerable psychological the epidermis or dermis which can be assess influence with a negative effect on quality of life by examination of patients with Wood’s light and emotional well-being.3 (365 nm). There are four types of melasma which are described on the basis of Wood’s light The most common age of melasma in adults examination: an epidermal type, a dermal type, women is between 30 years to 40 years, but it can a mixed type, and a fourth type, described in start earlier before 30 years or after 40 years, or patients of dark complexion, in which the lesions even seen in post-menopausal women. In fairer are not distinct on Wood’s light examination, due skin, it usually manifest earlier, whereas in darker to the increased number of melanosomes in the skin, it manifest late. Usually women observed dark skin individuals.6 this type of pirmentation in pregnancy or after the

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Different topical agents which affects on Karachi, in out-patient department, enrolling 73 pigmentation are hydroquinone, retinoic acid, patients. The research was done in six months kojic acid, azelaic acid, and chemical peels duration. Patient with resistant melasma who including glycolic, trichloroacetic acid, salicylic were meeting the inclusion criteria were included and lactic acid are in use for treating melasma. after taking an informed consent in the study. All of these have variable result and require long Patient who were pregnant and lactating women, term applications. Physical modalities like lasers patients with chronic liver, kidney, heart disease, and dermabrasion have also been used with connective tissue disease, dyscrasia, limited success. Side effects are observed with photodermatosis or hormonal diseases, patients these treatment options, especially on prolonged on hormonal treatment, facial dermatitis and usage which have limited efficacy and more those who had been treated for the melasma often the condition relapses on discontinuation within 4 weeks prior to study were excluded of therapy. As there is no satisfactory agents for from the study. A complete history was taken melasma, research is ongoing to develop newer, regarding the duration of pigmentation and the safer and advanced treatment for treating this treatment taken for the pigmentaion and entered psychosocial disorder which causes significant into the Performa. Modified MASI score were cosmetic disfigurement, and distress to the calculated on the first visit and after every 2 patient.7 weeks. Photograph of the face were taken after the consent at every visit from the same camera Conventially Tranexamic acid is a hemostatic at fix distance with natural light source. drug. It is temperature-stable and does not get easily oxidized.8 It is a lysine analogue with After aseptic measure, topical anesthesia cream antiplasmin activity and interferes with the was applied, 0.2 ml tranexamic acid diluted in 0.8 structure of plasminogen and preventing the ml normal saline was injected intradermally into binding of plasminogen to the lysine-binding the melasma lesion at 1 cm distance by using sites of keratinocytes.19,10 Due to low level of an insulin syringe with a 30-gauge needle. After Arachidonic acid there is decrease production the procedure patients were strickly advised to of prostaglandin which reduces melanocyte avoid sun and heat exposure for 6 to 8 hours. tyrosinase activity and melanogenesis11,12,13 and The procedure was repeated after 2 weeks for thus improves melasma.14,15 4 months. The results were evaluated by using the modified Melasma Area and Severity Index Acquired defective color vision, an active intra- (MASI) at baseline and then monthly. Only sun vascular clotting disorders, and hypersensitivity protection was advised to the patients. to Tranexamic acid are the contraindication of Tranxemanic acid. Furthermore, it should be cau- RESULTS tiously prescribed for people with cardiovascu- The results indicated that out of 73 patients 8 were lar disease, cerebrovascular disease, and those male while 65 were female (Table-I, Figure-1). using anti-platelets and anti- fibrinolytic agents. Out of 73 patients 10 (13.7%) patients had poor The commonly reported side effects of systemic response, 48 (65.8%) patients had fair response, Tranexamic acid are GI complaints (nausea, diar- 14 (19.1%) patients had good response and only 1 rhea, and abdominal pain).16 (1.4%) had excellent response (Table-II, Figure-2). Only 2 patients complaining of redness over the MATERIAL & METHODS affected area which subsided within a week, with The research is Cross-sectional analytic study, no other side effect noted, like infection, swelling conducted in the out-patient department of and local pain. dermatology; Dow University of Health Sciences,

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Improvement Total Poor Fair Good Excellent Count 1 5 2 0 8 Male % within Gender 12.5% 62.5% 25.0% 0.0% 100.0% Gender Count 9 43 12 1 65 Female % within Gender 13.8% 66.2% 18.5% 1.5% 100.0% Count 10 48 14 1 73 Total % within Gender 13.7% 65.8% 19.2% 1.4% 100.0% Table-I. Gender * improvement crosstabulation

Frequency Percent Valid Percent Cumulative Percent Valid Poor 10 13.7 13.7 13.7 Fair 48 65.8 65.8 79.5 Good 14 19.2 19.2 98.6 Excellent 1 1.4 1.4 100.0 Total 73 100.0 100.0 Table-II. Improvement

Figure-1. Figure-2.

DISCUSSION It is much safer, convenient and cheaper modality Melasma is one of the most common, aquired and show benefit in those patients who cannot and persistent hyperpigmentary disorders found apply topical agents frequently or develop mainly in Asian women and dark-skinned patients. irritation or acne with the topical agents. There is no exact causative agents or factors for melasma but it is precipiated or aggrevated Tranexamic acid is a medication used to treat by certain factors like sunlight, hormones and or prevent excessive blood loss from major pregnancy. It is very resistant to treatment and trauma, postpartum , surgery, tooth the main options are hydroquinone, azelaic acid, removal, nosebleeds, and heavy menstruation. kojic acid, Vitamin C and sun protection. It is a synthetic lysine analog, which have an antifibrinolytic activity by reversibly binding four Tranexamic acid is the newer addition in melasma. to five lysine receptor sites on plasminogen. It It can be used orally, topically and intralesionally. prevents pigmentation caused by ultraviolet light

352 www.theprofesional.com Professional Med J 2021;28(3):350-354. Intradermal tranexamic acid in melasma 4 by interfering with the structure of plasminogen 3. Freitag FM, Cestari TF, Leopoldo LR, Paludo P, Boza JC. and preventing the binding of plasminogen to the Effect of melasma on quality of life in a sample of women living in southern Brazil. J Eur Acad Dermatol lysine-binding sites of keratinocytes, and it also Venereol. 2008; 22:655–62. act on angiogenesis. 4. Ortonne JP, Arellano I, Berneburg M et al. A global survey In this research study we enrolled 73 patients who of the role of ultraviolet radiation and hormonal had taken convential treatment with no or partial influences in the development of melasma. J Eur Acad Dermatol Venereol 2009; 23: 1254–1262. response, majority had melasma for more than 5 years. Out of 73 patient 63 patients improved 5. Tamega Ade A, Miot LD, Bonfietti C, Gige TC, Marques while 10 patients did not show any improvement. ME, Miot HA. Clinical patterns and epidemiological Similar study conducted in Korea on 100 women characteristics of facial melasma in Brazilian women. J Eur Acad Dermatol Venereol. 2013; 27:151– by Lee et al in 2006, also showed significant 156 improvement of melasma.10 Another study conducted in India also showed that tranexamic 6. Nestor PS, Madhu AP, Syozo S, Thomas B, Jorge acid appear to be promising therapeutic option LS, et al, Melasma: A clinical, light microscopic, for melasma.17 ultrastructural, and immunofluorescence study. Journal of the American Academy of Dermatology. Volume 4, Issue 6, June 1981, Pages 698-710. Tranexamic acid is an economical option, appear promising and used as an adjuvant with other 7. Pawaskar MD, Parikh P, Markowski T, Mc Michael AJ, therapy. Further studies are however needed with Feldman SR, Balkrishan R. Melasma and its impact on health related QOL in Hispanic women. J Dermatolog increase concentration of tranexamic acid and Treat 2007; 18:5-9. with combination therapy. The limitation of the research study is that the size of the sample size 8. Fox C. From Tranexemic acid on freckles to can be larger for longer duration treatment. non-animal fillers: Patent, Literature finding. Cosmetics and Toiletries. Available at: http: //www. cosmeticsandtoiletries.com. Accessed September CONCLUSION 25,2011. Intradermal tranexamic acid is safe and effective treatment in melasma, side effects which may 9. Tse TW, Hui E. Tranexamic acid: An important adjuvant be observed by taking systemic tranexamic in the treatment of melasma. J Cosmet Dermatol 2013; 12:57-66. acid can be avoided by intradermal injections. It inhibits melanocyte activation and melanocyte 10. Sharma R, Mahajan VK, Mehta KS, Chauhan PS, Rawat proliferation which is due to ultraviolet light and R, Shiny TN. Therapeutic efficacy and safety of oral under the influence of hormones. It also inhibited tranexamic acid and that of tranexamic acid local neovascularization by inhibiting VEGF, and mast infiltration with microinjections in patients with melasma: a comparative study. Clin Exp Dermatol. cell-induced basement membrane damage. Thus 2017 Oct;42(7):728-734. doi: 10.1111/ced.13164. Epub improved pigmentation and erythema. It can be 2017 Jun 25. PMID: 28649780. used alone or as adjuvant therapy in resistant melasma. 11. Lee JH, Park JG, Lim SH, Kim JY, Ahn KY, Kim MY, et al. Localized intradermal microinjection of tranexemic Copyright© 08 July, 2020. acid for treatment of melasma in Asian patients: A preliminary clinical report. Dermatol Surg 2006; REFERENCES 32:626-31. 1. Sarkar R, Puri P, Jain RK, Singh A, Desai A. Melasma in men: A clinical, etiological and histological study. J 12. Wang N, Zhang L, Miles L, Hoover-Plow J. Plasminogen Eur Acad Dermatol Venereol 2010; 24:768-72. regulates pro-opiomelanocortin processing. J Thromb Haemost. 2004; 2:785–96. 2. Prignano F1, Ortonne JP, Buggiani G, Lotti T. Therapeutical approaches in melasma. Dermatol 13. Chang WC, Shi GY, Chow YH, Chang LC, Hau JS, Lin MT, Clin. 2007 Jul; 25(3):337-42, viii. et al. Human plasmin induces a receptor-mediated arachidonate release coupled with G proteins in endothelial cells. Am J Physiol. 1993; 264:C271–81.

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14. Maeda K, Naganuma M. Topical trans-4-aminomethyl 16. Lee HC, Thng TG, Goh CL. Oral tranexamic acid cyclohexanecarboxylic acid prevents ultraviolet (TA) in the treatment of melasma: A retrospective radiation-induced pigmentation. J Photochem analysis. J Am Acad Dermatol 2016; 75:385-92. Photobiol B. 1998; 47:136–41. 17. Budamakuntla L, Loganathan E, Suresh D, Shanmugam 15. Kondou S, Okada Y, Tomita Y. Clinical study of effect S, Dongare A, Prabhu N, et al. A randomised, of tranexamic acid emulsion on melasma and open-label, comparative study of tranexamic freckles. Skin Res. 2007; 6:309–15. acid microinjections and tranexamic acid with microneedling in patients with melasma. J Cutan Aesthet Surg. 2013; 6(3):139.

AUTHORSHIP AND CONTRIBUTION DECLARATION

Sr. # Author(s) Full Name Contribution to the paper Author(s) Signature 1 Tayyaba Iqbal Collection of data.

2 Sadaf Ahmed Asim Interpretation and theorizing.

3 Madiha Sajid Data analysis.

4 Sadia Hafeez Collection of data.

5 Maria Mansoor Research design.

6 Reema Mirza Compling the data.

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