Abstract
Introduction: Acne vulgaris is a common inflammatory skin disorder affecting the sebaceous glands–rich areas, including the face, chest, and back. It typically arises during adolescence but can persist or appear in adulthood. Recent findings suggest that histamine, via H1 receptors on sebocytes, further contributes to inflammation and sebum secretion. Desloratadine, an H1 receptor antagonist, has anti-inflammatory effects and reduces sebum squalene levels, supporting potential as an adjunctive acne therapy. We assessed whether adding desloratadine to isotretinoin improves outcomes compared to isotretinoin monotherapy.
Methods: Following PRISMA guidelines, we searched PubMed, Web of Science, and Scopus targeting randomized controlled trials (RCTs) comparing isotretinoin plus desloratadine versus isotretinoin alone. Eligible studies reported the Global Acne Grading System (GAGS) score, inflammatory lesion count, or non-inflammatory lesion count. Results were pooled and expressed as differences (MD) with 95% confidence intervals (CI).
Results: Six RCTs, including 424 patients, met the inclusion criteria. Combination therapy demonstrated greater improvement in GAGS score (pooled MD −1.81, 95% CI [−2.52; −1.1], P < 0.00001). However, no significant differences were observed in inflammatory lesions (pooled MD 0.26, 95% CI [−1.01; 1.54], P = 0.68) or non-inflammatory lesions (pooled MD 0.30, 95% CI [−2.24; 2.84], P = 0.82). The addition of desloratadine to isotretinoin improved treatment efficacy and showed trends toward fewer flares and dry lips, although these differences did not reach statistical significance.
Conclusion: Desloratadine appears to enhance the efficacy and tolerability of isotretinoin, supporting its position as a promising adjunctive therapy for acne management.
References
1. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012: 361 [PMID: 21880356, https://doi.org/10.1016/S0140-6736(11)60321-8]
2. Akuffo-Addo E, Ramsay K, Mohsen S, Boisvert J, Mukovozov I. Visible Light in the Treatment of Acne Vulgaris. J Cutan Med Surg. 2024: 567 [PMID: 39056372, https://doi.org/10.1177/12034754241265697]
3. Bharti S, Vadlamudi HC. A strategic review on the involvement of receptors, transcription factors and hormones in acne pathogenesis. J Recept Signal Transduct Res. 2021: 105 [PMID: 32787477, https://doi.org/10.1080/10799893.2020.1805626]
4. Pandey D, Agrawal S. Efficacy of Isotretinoin and Antihistamine versus Isotretinoin Alone in the Treatment of Moderate to Severe Acne: A Randomised Control Trial. Kathmandu Univ Med J (KUMJ). 2019: 14 [PMID: 31734672,
5. Artuc M, Steckelings UM, Grutzkau A, Smorodchenko A, Henz BM. A long-term coculture model for the study of mast cell-keratinocyte interactions. J Invest Dermatol. 2002: 411 [PMID: 12190864, https://doi.org/10.1046/j.1523-1747.2002.01838.x]
6. Lee HE, Chang IK, Lee Y, Kim CD, Seo YJ, Lee JH, Im M. Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study. J Eur Acad Dermatol Venereol. 2014: 1654 [PMID: 25081735, https://doi.org/10.1111/jdv.12403]
7. Hazarika N, Yadav P, Bagri M, Chandrasekaran D, Bhatia R. Oral isotretinoin with desloratadine compared with oral isotretinoin alone in the treatment of moderate to severe acne: a randomized, assessor-blinded study. Int J Dermatol. 2024: 929 [PMID: 38546101, https://doi.org/10.1111/ijd.17129]
8. Zouboulis CC. Sebaceous gland receptors. Dermatoendocrinol. 2009: 77 [PMID: 20224688, https://doi.org/10.4161/derm.1.2.7804]
9. Pelle E, McCarthy J, Seltmann H, Huang X, Mammone T, Zouboulis CC, Maes D. Identification of histamine receptors and reduction of squalene levels by an antihistamine in sebocytes. J Invest Dermatol. 2008: 1280 [PMID: 18007585, https://doi.org/10.1038/sj.jid.5701160]
10. Geha RS, Meltzer EO. Desloratadine: A new, nonsedating, oral antihistamine. J Allergy Clin Immunol. 2001: 751 [PMID: 11295678, https://doi.org/10.1067/mai.2001.114239]
11. Wu RL, Anthes JC, Kreutner W, Harris AG, West RE, Jr. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 Receptor. Int Arch Allergy Immunol. 2004: 313 [PMID: 15564772, https://doi.org/10.1159/000082325]
12. Wozna J, Baloniak A, Stepka J, Polanska A, Mojs E, Zaba R. Efficacy of Combined Oral Isotretinoin and Desloratadine or Levocetirizine vs. Isotretinoin Monotherapy in Treating Acne Vulgaris: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Biomedicines. 2025: 1847 [PMID: 40868102, https://doi.org/10.3390/biomedicines13081847]
13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hrobjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021: n71 [PMID: 33782057, https://doi.org/10.1136/bmj.n71]
14. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernan MA, Hopewell S, Hrobjartsson A, Junqueira DR, Juni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019: l4898 [PMID: 31462531, https://doi.org/10.1136/bmj.l4898]
15. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997: 629 [PMID: 9310563, https://doi.org/10.1136/bmj.315.7109.629]
16. Terrin N, Schmid CH, Lau J, Olkin I. Adjusting for publication bias in the presence of heterogeneity. Stat Med. 2003: 2113 [PMID: 12820277, https://doi.org/10.1002/sim.1461]
17. El-Ghareeb MI, Kandeel AH, Khayrullah NM. Efficacy and safety of combined oral isotretinoin and desloratadine vs. isotretinoin alone in acne vulgaris: a comparative study. Arch Dermatol Res. 2025: 689 [PMID: 40204949, https://doi.org/10.1007/s00403-025-04145-7]
18. Asilian A, Abedini M, Iraji F, Jahanshahi A. Comparing the efficacy of oral isotretinoin alone and in combination with desloratadine in treating moderate to severe acne vulgaris: a randomized clinical trial. Iranian Journal of Dermatology. 2024: 153
19. Van TN, Thi LD, Trong HN, Van TC, Minh TT, Minh PPT, Huu ND, Cam VT, Huyen ML, Hau KT, Gandolfi M, Satolli F, Feliciani C, Tirant M, Vojvodic A, Lotti T. Efficacy of Oral Isotretinoin in Combination with Desloratadine in the Treatment of Common Vulgaris Acne in Vietnamese Patients. Open Access Maced J Med Sci. 2019: 217 [PMID: 30745963, https://doi.org/10.3889/oamjms.2019.054]
20. Mansoor M, Saeed W, Khan FN, Latif A, Altaf F. Efficacy of oral isotretinoin in combination with desloratadine versus oral isotretinoin alone in the treatment of moderate acne vulgaris2024:
21. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003: 582 [PMID: 12719681, https://doi.org/10.1097/01.MLR.0000062554.74615.4C]
22. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016: 945 [PMID: 26897386, https://doi.org/10.1016/j.jaad.2015.12.037]
23. Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004: 2203 [PMID: 15548781, https://doi.org/10.1056/NEJMra033121]
24. Tanghetti EA. The role of inflammation in the pathology of acne. J Clin Aesthet Dermatol. 2013: 27 [PMID: 24062871,
25. Dreno B, Dagnelie MA, Khammari A, Corvec S. The Skin Microbiome: A New Actor in Inflammatory Acne. Am J Clin Dermatol. 2020: 18 [PMID: 32910436, https://doi.org/10.1007/s40257-020-00531-1]

This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2026 Ahmed S Mohamed, Mazen Kafienah, Meena Rabi, Paul Fabian, Ali Gebril Ali, Mohamed Ali Abdel Rahman, Ayla Amjad, Eslam seddik

