Evaluation of the Safety of Low-Dose Topical Imiquimod Cream on Frontal Sinus Ostium Stenosis Following Endoscopic Sinus Surgery: A Pilot Clinical Trial
Abstract
Introduction: Frontal sinus ostium stenosis is a common postoperative challenge in endoscopic sinus surgery, potentially leading to disease recurrence. Imiquimod is an immunomodulatory agent with anti-inflammatory and antifibrotic properties, recently gaining attention in experimental studies.
Objective: To evaluate the safety of low-dose topical imiquimod cream in reducing the rate of frontal sinus ostium stenosis following endoscopic sinus surgery.
Methods: This pilot randomized intra-patient controlled clinical trial was conducted on 20 patients with CRSwNP. Each patient underwent bilateral Draf 2a surgery. One frontal sinus was randomly assigned to receive Gelfoam impregnated with 5% imiquimod cream, with applications repeated in the second and fourth postoperative weeks. The contralateral side served as the control. Patients were assessed at week 4 and month 3 postoperatively via endoscopic and CT imaging. Endoscopic scores were based on the DIP system, and the STDR ratio was evaluated using 3D CT reconstruction. Data analysis was performed using paired t-tests and Wilcoxon tests at a significance level of 0.05.
Results: At three months post-surgery, STDR was significantly lower on the intervention side (p < 0.05), indicating reduced soft tissue density and opacification. Endoscopic evaluation also showed a marked improvement in polyp and inflammation scores on the treated side. No significant differences were observed at one month. No major local or systemic adverse effects were reported.
Conclusion: Topical application of low-dose imiquimod cream after endoscopic sinus surgery may effectively reduce inflammation, discharge, polyp formation, and opacification in the frontal sinus, and may be considered a safe preventive option for ostium stenosis. Larger trials are recommended to confirm these findings
2. Sedaghat AR, Kuan EC, Scadding GK. Epidemiology of chronic rhinosinusitis: prevalence and risk factors. J Allergy Clin Immunol Pract. 2022;10(6):1395-403. https://doi.org/10.1016/j.jaip.2022.01.016
3. Wautlet A, Bachert C, Desrosiers M, Hellings PW, Peters AT. The Management of Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) With Biologics. J Allergy Clin Immunol Pract. 2023 Sep;11(9):2642-51. https://doi.org/10.1016/j.jaip.2023.04.054
4. Clejan S, Mandrea E, Pandrea IV, Dufour J, Japa S, Veazey RS. Immune responses induced by intranasal imiquimod and implications for therapeutics in rhinovirus infections. J Cell Mol Med. 2005 Apr-Jun;9(2):457-61. https://doi.org/10.1111/j.1582-4934.2005.tb00370.x
5. Fernández-Casado A, Pujol RM, Amat M, Gallardo F. Successful treatment of intranasal papillomata with imiquimod cream in a human immunodeficiency virus positive patient. J Laryngol Otol. 2009 Feb;123(2):240-2.https://doi.org/10.1017/S0022215108002570
6. Jeong SS, Chen T, Nguyen SA, Edwards TS, Schlosser RJ. Correlation of polyp grading scales with patient symptom scores and olfaction in chronic rhinosinusitis: a systematic review and meta-analysis. Rhinology. 2022 Apr 19. https://doi.org/10.4193/rhin22.011
7. Schön MP, Schön M. Imiquimod: mode of action. Br J Dermatol. 2007 Dec;157 Suppl 2:8-13. https://doi.org/10.1111/j.1365-2133.2007.08265.x
8. Beutner KR, Tyring SK, Trofatter KF Jr, Douglas JM Jr, Spruance S, Owens ML, et al. Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts. Antimicrob Agents Chemother. 1998 Apr;42(4):789-94. https://doi.org/10.1128/AAC.42.4.789
9. Lee YS, Kim JH, Lim DH. Urine Microbe-Derived Extracellular Vesicles in Children With Asthma. Allergy Asthma Immunol Res. 2021 Jan;13(1):75-87. https://doi.org/10.4168/aair.2021.13.1.75
10. Kienzler JL, et al. Pharmacokinetics and tolerance of topical imiquimod. Clin Pharmacokinet. 2003;42(4):305-19. 11. RL Miller, JF Gerster, ML Owens, HB Slade, Ma Tomai.Imiquimod: a novel immune response modifier. Int J Immunopharmacol. 1999;21(1):1-14. https://doi.org/10.1016/S0192-0561(98)00068-X
12. Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464.
13. Patel GK, et al. Imiquimod in superficial basal cell carcinoma: review. Br J Dermatol. 2004;150(4):731-6. https://doi.org/10.1046/j.1365-2133.2001.04127.x
14. Schmitt J, et al. Intraindividual randomized split-side trial design in dermatology. Br J Dermatol. 2009;161(6):1220-2.
| Files | ||
| Issue | Vol 8 No 3 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Chronic rhinosinusitis nasal polyps frontal sinus imiquimod endoscopic sinus surgery STDR | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
