Clinical Oral Investigations

, Volume 22, Issue 3, pp 1319–1325 | Cite as

Diclofenac sodium gel therapy as an alternative to actinic cheilitis

  • Amanda Katarinny Goes Gonzaga
  • Patrícia Teixeira de Oliveira
  • Éricka Janine Dantas da Silveira
  • Lélia Maria Guedes Queiroz
  • Ana Miryam Costa de Medeiros
Original Article



Actinic cheilitis (AC) is a potentially malignant lesion caused by prolonged exposure to ultraviolet light. The aim of this research was to analyze the efficacy of diclofenac sodium 3% gel in the treatment of this condition, through clinical follow-up.


Thirty-one patients diagnosed with AC were instructed to perform a topical application of the gel three times a day for a period of 90 days. In each visit, a digital photography was obtained for verified progress and response to treatment. Two researchers evaluated all images after treatment was completed and assigned the following scores regarding clinical aspect of the lip: 1, complete improvement; 2, partial improvement; 3, no changes; 4, worsening of the clinical condition. In addition, the patients’ tolerability to the drug and their satisfaction after treatment were evaluated.


Twelve cases abandoned the treatment for reasons unrelated to the study. Ten participants showed total remission of all clinical features of the lesion and three had partial improvement of the characteristics. One participant presented worsening of clinical condition, and in five cases, treatment was discontinued due to development of mild adverse effects at the site of gel application. Regarding satisfaction analyses and tolerability to the drug, from 14 patients who completed treatment without adverse effects or complications, most agreed fully that they were satisfied with the therapy (n = 11) and that the drug was not irritating to the mouth (n = 9). Patients are being monitored without clinical signs of recurrence and/or progression of the lesions.


Topical application of the drug has provided a convenient and well tolerated in most cases.

Clinical relevance

Diclofenac sodium gel (3%) may be a promising alternative for treatment of actinic cheilitis.


Cheilitis Diclofenac Cyclooxygenase-2 Cyclooxygenase inhibitors 



The work was supported by the Department of Oral–Federal University of Rio Grande do Norte.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Federal University of Rio Grande do Norte (Protocol 1.024.559).

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Cavalcante AS, Anbinder AL, Carvalho YR (2008) Actinic cheilitis: clinical and histological features. J Oral Maxillofac Surg 66:498–503CrossRefPubMedGoogle Scholar
  2. 2.
    Piñera-Marque K, Lourenço SV, Silva LF, Sotto MN, Carneiro PC (2010) Actinic lesions in fishermen’s lower lip: clinical, cytopathological and histopathologic analysis. Clinics (Sao Paulo) 65:363–367CrossRefGoogle Scholar
  3. 3.
    Ulrich M, González S, Lange-Asschenfeldt B et al (2010) Non-invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy. J Eur Acad Dermatol Venereol 25:276–284CrossRefGoogle Scholar
  4. 4.
    De Souza EEL, Costa DC, da Silveira EJD, Lima KC et al (2012) Prevalence and factors associated to actinic cheilitis in beach workers. Oral Dis 18:575–579CrossRefGoogle Scholar
  5. 5.
    Lopes MLDS, Silva Júnior FL, Lima KC, Oliveira PT, da Silveira EJD (2015) Clinicopathological profile and management of 161 cases of actinic cheilitis. An Bras Dermatol 90:505–512CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Savage NW, McKay C, Faulker C (2010) Actinic cheilitis in dental practice. Aust Dent J 55:78–84CrossRefPubMedGoogle Scholar
  7. 7.
    Vieira RA, Minicucci EM, Marques ME, Marques AS (2011) Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and imumunogenetic aspects. An Bras Dermatol 87:105–114CrossRefGoogle Scholar
  8. 8.
    Wood NH, Khammissa R, Meyerov R, Lemmer J, Feller L (2011) Actinic cheilitis: a case report and a review of the literature. Eur J Dent 5:101–106PubMedPubMedCentralGoogle Scholar
  9. 9.
    Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E (2008) Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med 37:127–133CrossRefPubMedGoogle Scholar
  10. 10.
    Martins-Filho PR, Da Silva LC, Piva MR (2011) The prevalence of actinic cheilitis in farmers in a semi-arid northeastern region of Brazil. Int J Dermatol 50:1109–1114CrossRefPubMedGoogle Scholar
  11. 11.
    Cury PR, Furuse C, de Araújo NS, de Araújo VC (2007) Signal transducer and activator of transcription-3 expression and activation is dysregulated in actinic cheilitis. J Cutan Pathol 34:606–611CrossRefPubMedGoogle Scholar
  12. 12.
    Liu W, Wang YF, Zhou HW, Shi P, Zhou ZT, Tang GY (2010) Malignant transformation of oral leukoplakia: a retrospective cohort study of 218 Chinese patients. BMC Cancer 10:685CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ulrich C, Forschner T, Ulrich M, Stockfleth E, Sterry W, Termeer C (2007) Management of actinic cheilitis using diclofenac 3% gel: a report of six cases. Br J Dermatol 156:43–46CrossRefPubMedGoogle Scholar
  14. 14.
    Berking C, Herzinger T, Flaig MJ, Brenner M, Borelli C, Degitz K (2007) The efficacy of photodynamic therapy in actinic cheilitis of the lower lip: a prospective study of 15 patients. Dermatol Surg 33:825–830PubMedGoogle Scholar
  15. 15.
    Nelson CG, Spencer J, Nelson CG Jr (2007) A single-arm, open-label efficacy and tolerability study of diclofenac sodium 3% gel for the treatment of actinic keratosis of the upper and lower lip. J Drugs Dermatol 6:712–717PubMedGoogle Scholar
  16. 16.
    Orenstein A, Goldan O, Weissman O, Winkler E, Haik J (2007) A new modality in the treatment of actinic cheilitis using the Er:YAG laser. J Cosmet Laser Ther 9:23–25CrossRefPubMedGoogle Scholar
  17. 17.
    Pirard D, Vereecken P, Mélot C, Heenen M (2005) Three percent diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses: a meta-analysis of the recent studies. Arch Dermatol Res 297:185–189CrossRefPubMedGoogle Scholar
  18. 18.
    Lima GS, Silva GF, Gomes APN, Araújo LMA, Salum FG (2010) Diclofenac in hyaluronic acid gel: an alternative treatment for actinic cheilitis. J Appl Oral Sci 18:533–537CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Kose O, Koc E, Erbil AH, Caliskan E, Kurumlu Z (2008) Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis. J Dermatol Treat 19:159–163CrossRefGoogle Scholar
  20. 20.
    Dirschka T, Bierhoff E, Pflugfelder A, Garbe C (2010) Topical 3.0% diclofenac in 2.5% hyaluronic acid gel induces regression of cancerous transformation in actinic keratoses. J Eur Acad Dermatol Venereol 24:258–263CrossRefPubMedGoogle Scholar
  21. 21.
    Haque T, Rahman KM, Thurston DE, Hadgraft J, Lane ME (2015) Topical therapies for skin cancer and actinic keratosis. Eur J Pharm Sci 77:279–289CrossRefPubMedGoogle Scholar
  22. 22.
    Shah AY, Doherty SD, Rosen T (2010) Actinic cheilitis: a treatment review. Int J Dermatol 49:1225–1234CrossRefPubMedGoogle Scholar
  23. 23.
    Masferrer JL, Leahy KM, Koki AT et al (2000) Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60:1306–1311PubMedGoogle Scholar
  24. 24.
    Cha JD, Li S, Cha IH (2011) Association between expression of embryonic lethal abnormal vision-like protein HuR and cyclooxygenase-2 in oral squamous cell carcinoma. Head Neck 33:627–637CrossRefPubMedGoogle Scholar
  25. 25.
    Nagatsuka H, Siar CH, Tsujigiwa H et al (2012) Heparanase and cyclooxygenase-2 gene and protein expressions during progression of oral epithelial dysplasia to carcinoma. Ann Diagn Pathol 16:354–361CrossRefPubMedGoogle Scholar
  26. 26.
    Seyedmajidi M, Shafaee S, Siadati S, Khorasani M, Bijani A, Ghasemi N (2014) Cyclo-oxygenase-2 expression in oral squamous cell carcinoma. J Cancer Res Ther 10:1024–1029CrossRefPubMedGoogle Scholar
  27. 27.
    Wang Z, Liu J, Liu HB, Ye M, Zhang YF, Yang DS (2014) Abnormal COX2 protein expression may be correlated with poor prognosis in oral cancer: a meta-analysis. Biomed Res Int 2014:1–9Google Scholar
  28. 28.
    Byatnal AA, Byatnal A, Sen S, Guddattu V, Solomon MC (2015) Cyclooxygenase-2—an imperative prognostic biomarker in oral squamous cell carcinoma—an immunohistochemical study. Pathol Oncol Res 4:1123–1131CrossRefGoogle Scholar
  29. 29.
    Dorsam RT, Gutkind JS (2007) G-protein-coupled receptors and cancer. Nat Rev Cancer 7:79–94CrossRefPubMedGoogle Scholar
  30. 30.
    Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444CrossRefPubMedGoogle Scholar
  31. 31.
    Trinchieri G (2011) Innate inflammation and cancer: is it time for cancer prevention? Med Rep F1000:3–11Google Scholar
  32. 32.
    Rojas IG, Martínez A, Brethauer U et al (2009) Actinic cheilitis: epithelial expression of COX-2 and its association with mast cell tryptase and PAR-2. Oral Oncol 45:284–290CrossRefPubMedGoogle Scholar
  33. 33.
    Rojas IG, Boza YV, Spencer ML, Flores M, Martínez A (2012) Increased fibroblast density in actinic cheilitis: association with tryptase-positive mast cells, actinic elastosis and epithelial p53 and COX-2 expression. J Oral Pathol Med 41:27–33CrossRefPubMedGoogle Scholar
  34. 34.
    Maltusch A, Röwert-Huber J, Matthies C, Lange-Asschenfeldt S, Stockfleth E (2011) Modes of action of diclofenac 3%/hyaluronic acid 2.5% in the treatment of actinic keratosis. J Dtsch Dermatol Ges 9:1011–1017PubMedGoogle Scholar
  35. 35.
    Rivers JK, DI ML (1997) An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratosis. Arch Dermatol 133:1239–1242CrossRefPubMedGoogle Scholar
  36. 36.
    Fariba I, Ali A, Hossein SA, Atefeh S, Atarzadeh Behbahan AS (2006) Efficacy of 3% diclofenac gel for the treatment of actinic keratoses: a randomized, double-blind, placebo controlled study. Indian J Dermatol Venereol Leprol 75:346–349CrossRefGoogle Scholar
  37. 37.
    Smith SR, Morhenn VB, Piacquadio DJ (2006) Bilateral comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% 5-fluorouracil cream in the treatment of actinic keratoses of the face and scalp. J Drugs Dermatol 5:156–159PubMedGoogle Scholar
  38. 38.
    Berlin JM, Rigel DS (2008) Diclofenac sodium 3% gel in the treatment of actinic keratoses postcryosurgery. J Drugs Dermatol 7:669–673PubMedGoogle Scholar
  39. 39.
    Ulrich M, Stockfleth E (2009) Field treatment of actinic keratoses—focus on COX-2-inhibitors. Actas Dermosifiliogr 2:55–58CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Amanda Katarinny Goes Gonzaga
    • 1
    • 2
  • Patrícia Teixeira de Oliveira
    • 1
  • Éricka Janine Dantas da Silveira
    • 1
  • Lélia Maria Guedes Queiroz
    • 1
  • Ana Miryam Costa de Medeiros
    • 1
  1. 1.Postgraduate Program in Oral PathologyFederal University of Rio Grande do NorteNatalBrazil
  2. 2.Department of DentistryUniversidade Federal do Rio Grande do NorteNatalBrazil

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