Efficacy of Topical 10% Isoniazid Cream Versus Triple Combination Cream (Kligman's Formula) in the Treatment of Mixed Melasma

Saadia  Jabeen; Summaya  Saleem; Asfa  Falak; Muhammad  Tanveer; Laila  Irshad; Rabia  Abid

doi:10.54112/bcsrj.v6i6.2140

Authors

Saadia Jabeen Department of Dermatology, CMH, Gujranwala, Pakistan
Summaya Saleem Department of Dermatology, CMH, Gujranwala, Pakistan
Asfa Falak Department of Dermatology, CMH, Gujranwala, Pakistan
Muhammad Tanveer Department of Medical Specialists, CMH Gujranwala, Pakistan
Laila Irshad Department of Dermatology, CMH, Gujranwala, Pakistan
Rabia Abid Department of Dermatology, CMH, Gujranwala, Pakistan

DOI:

https://doi.org/10.54112/bcsrj.v6i6.2140

Keywords:

Adverse effects, Hyperpigmentation, Isoniazid, Kligman’s formula, Melasma, Skin lightening, Topical therapy, Triple combination

Abstract

Melasma is an acquired pigmentary skin disorder characterized by symmetrical brown patches, most commonly on the face. The standard treatment involves topical triple-combination cream (Kligman's formula), but prolonged use is associated with adverse effects. Objectives: To compare the efficacy and safety of topical 10% isoniazid cream versus triple combination cream in the treatment of mixed melasma. Methods: This study was conducted at the Department of Dermatology, CMH Gujranwala, from 1st Sep 2024 to 31st March 2025. A total of 140 patients clinically diagnosed with mixed melasma were randomized into two groups of 70 each. Group A received 10% isoniazid cream, and Group B received the standard triple-combination cream, applied once daily at night for 8 weeks. Both groups used broad-spectrum sunscreen during the day. Efficacy was assessed using the modified Melasma Area and Severity Index (mMASI) and the physician global assessment (PGA). Adverse effects were also recorded. Results: Group A showed a greater mean reduction in mMASI score (5.7 ± 1.4) than Group B (4.4 ± 1.6), with a significant p-value (0.001). Excellent improvement (≥75%) was achieved in 40.0% of Group A, compared with 22.9% in Group B. Fewer adverse effects were reported in the isoniazid group. Conclusion: Topical 10% isoniazid cream was more effective and better tolerated than the triple combination cream for managing mixed melasma.

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References

Abdalla MA. Melasma clinical features, diagnosis, epidemiology, and etiology: an update review. Siriraj Med J. 2021;73(12):841-850. https://doi.org/10.33192/Smj.2021.109

Dharman BK, Sridhar S. Diffuse facial melanosis: an overview of etiology and dermoscopic findings. J Skin Sex Transm Dis. 2020;2(2):86-93. https://doi.org/10.25259/JSSTD_42_2019

Mpofana N, Chibi B, Visser T, Paulse M, Finlayson AJ, Ghuman S, et al. Treatment of melasma on darker skin types: a scoping review. Cosmetics. 2023;10(1):25. https://doi.org/10.3390/cosmetics10010025

Espósito ACC, Cassiano DP, da Silva CN, Lima PB, Dias JAF, Hassun K, et al. Update on melasma. Part I: pathogenesis. Dermatol Ther (Heidelb). 2022;12(9):1967-1988. https://doi.org/10.1007/s13555-022-00779-x

Bostan E, Cakir A. The dermoscopic characteristics of melasma in relation to different skin phototypes, distribution patterns, and Wood lamp findings: a cross-sectional study of 236 melasma lesions. Arch Dermatol Res. 2023;315(7):1927-1938. https://doi.org/10.1007/s00403-023-02584-8

Elethawi AM, Al-Gurairi FT. The impact of intense-pulsed light and modified Kligman’s formula for management of moderate to severe melasma: a comparative study. J Adv Med Med Res. 2024;36(2):1-8. https://doi.org/10.9734/jammr/2024/v36i25362

Vasam M, Korutla S, Bohara RA. Acne vulgaris: a review of the pathophysiology, treatment, and recent nanotechnology-based advances. Biochem Biophys Rep. 2023;36:101578. https://doi.org/10.1016/j.bbrep.2023.101578

Khan SR, Manialawy Y, Siraki AG. Isoniazid and host immune system interactions: a proposal for a novel comprehensive mode of action. Br J Pharmacol. 2019;176(24):4599-4608. https://doi.org/10.1111/bph.14867

Babu D, Morgan AG, Reiz B, Whittal RM, Almas S, Lacy P, et al. Eosinophil peroxidase oxidizes isoniazid to form the active metabolite against Mycobacterium tuberculosis, isoniazid-NAD+. Chem Biol Interact. 2019;305:48-53. https://doi.org/10.1016/j.cbi.2019.03.019

Netcharoensirisuk P, Abrahamian C, Tang R, Chen CC, Rosato AS, Beyers W, et al. Flavonoids increase melanin production and reduce proliferation, migration, and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2. Sci Rep. 2021;11(1):8515. https://doi.org/10.1038/s41598-021-88196-6

Bertotti PP, Cé R. Melasma: understanding its complexity and accurate therapeutic approaches. Rev Cient Sophia. 2024;16(1):878-883. DOI not available.

Nasimi M, Ghiasi M, Lajevardi V, Nasiri F, Shakoei S. A split-face comparison of fractional erbium: YAG laser plus Kligman’s formula vs Kligman’s formula monotherapy for facial melasma. Arch Dermatol Res. 2022;314(8):791-797. https://doi.org/10.1007/s00403-021-02294-z

Sankar J, Chauhan A, Singh R, Mahajan D. Isoniazid historical development, metabolism-associated toxicity, and a perspective on its pharmacological improvement. Front Pharmacol. 2024;15:1441147. https://doi.org/10.3389/fphar.2024.1441147

Ahramiyanpour N, Mahmoudi Z, Nezhad NZ, Khazaeli P, Amiri R, Kasraee B. Topical isoniazid as a novel treatment for melasma: a randomized, double-masked, vehicle-controlled clinical trial. J Cosmet Dermatol. 2024;23(8):2636-2643. https://doi.org/10.1111/jocd.16320

Asadullah K, Ghafoor R, Sanawar P, Jabeen N, Siddiqui FI, Qadir M. Comparison of the efficacy of the combination of TAM formula versus the Kligman formula for melasma at a tertiary care hospital in Karachi. J Popul Ther Clin Pharmacol. 2024;31(1):649-655. https://doi.org/10.53555/jptcp.v31i1.4063

Bertold C, Fontas E, Singh T, Gastaut N, Ruitort S, Wehrlen Pugliese S, et al. Efficacy and safety of a novel triple combination cream compared to Kligman’s trio for melasma: a 24-week double-masked prospective randomized controlled trial. J Eur Acad Dermatol Venereol. 2023;37(12):2601-2607. https://doi.org/10.1111/jdv.19455

Basit A, Rahman A, Uddin R. Oral tranexamic acid with triple combination cream (fluocinolone, hydroquinone, and tretinoin) versus triple combination cream alone in treatment of melasma. J Ayub Med Coll Abbottabad. 2021;33(2):293-298. DOI not available.

Kamal K, Paracha MM, Idrees N, Bakhtiar R, Ullah I, Nadeem M. Effectiveness of triple combination cream and 30% glycolic acid peel versus triple combination cream alone in treating epidermal melasma. Med Forum Mon. 2020;31(3):53-57. DOI not available.

Colón LE, Johnson LA. Successful treatment of moderate to severe melasma with triple-combination cream and glycolic acid peels: a pilot study. Cutis. 2008;82:372-378. DOI not available.

Akhtar N, Hassan T, Shahzad MK, Aliya N, Yousaf S, Anwar M. Comparison between efficacy of serial glycolic acid peel with modified Kligman’s regimen vs modified Kligman’s regimen alone in epidermal melasma. Pak J Health Sci. 2024;5(3):29-33. https://doi.org/10.54393/pjhs.v5i03.1284