COMMENTARY Commentary on Photodynamic Therapy of Actinic Cheilitis Actinic cheilitis (AC) poses a therapeutic challenge and urgency because of its precancerous potential, recalcitrance, and high rate of metastasis when it has progressed to squamous cell carcinoma (SCC). Affecting an estimated 5% of the general population with a prevalence of 11.4% to 16.7% among farmers and fishermen, AC progresses to SCC at reported rates ranging from 1.4% to 36% over an interval of 1 to 30 years.1–6 Once SCC of the lower lip has occurred, metastasis rates are high at 17% to 25%.7–9 To date, most published reviews of the treatment of AC have included cryotherapy, electrocautery, topical agents such as fluorouracil and imiquimod, carbon dioxide (CO2) laser resurfacing, and vermillionectomy.10–12 In this issue of Dermatologic Surgery, Yazdani Abyaneh and colleagues13 compellingly demonstrate that photodynamic therapy (PDT) should be included among the primary therapeutic options for the treatment of AC. In comparing efficacy rates among the various treatment options available for AC, PDT seems to be comparable in efficacy to other modalities. Although the complete clinical cure rate (CR) and histologic cure rate (HR) for cryotherapy, electrodesiccation, and CO2 laser resurfacing have not been reported in the literature, the author may compare cure rates between topical therapy and PDT for AC. In 1 study of topical 5-fluorouracil treatment of AC, the reported CR was 50% and HR was 40%.14 Regarding the imiquimod treatment of AC, the CR was 100% in 1 small case series and the HR was 40% in another.15,16 In comparison, in this review, Yazdani Abyaneh and colleagues calculated an average CR for PDT of 62% at a mean follow-up interval of 3 to 30 months, with an HR of 47% at 1.5 to 18 months of follow-up. Thus,
the efficacy rates reported in this systematic review of PDT for AC are similar to those reported for other treatment modalities. In assessing relative safety among AC treatments, important advantages to PDT for AC are the excellent side effect profile and cosmetic outcome in contrast to other therapeutic options. Ablative therapies, such as cryotherapy and electrodessication, carry the disadvantages of hypopigmented scarring and long recovery times.10,17 Ablative CO2 laser resurfacing also causes hypopigmented scarring and has a 2-week recovery time.10,17 Topical 5-fluorouracil and imiquimod are associated with severe and unpredictable side effects, including erythema, crusting, ulceration, scarring, and poor cosmetic outcomes.3,10,15,18–22 Treatment of AC with topical 5% imiquimod 3 times per week for 5 to 6 weeks resulted in clearing at 4 weeks of follow-up; however, 60% of patients experienced a moderate-to-severe reaction of erythema, induration, erosions, or ulcerations.15 In extreme cases, surgical treatment with vermilionectomy has been performed but carries a high incidence of scarring and poor cosmetic outcome.10 In contrast, this review reports that patients with AC treated with PDT experienced only transient local reactions and few adverse events, with the primary concern being perioperative pain in a minority of cases treated with methyl aminolevulinic acid and red light PDT. Overall, the review demonstrated few adverse events and excellent post-treatment cosmesis with PDT for AC. Thus, the need for additional treatment options for AC, and the comparable efficacy and superior safety profile associated with PDT for AC that are described in this review, provide a compelling argument for
Supported by research grants from Alma, Syneron, Deka, and Lancome. The author has indicated no significant interest with commercial supporters. © 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2015;41:199–200 DOI: 10.1097/DSS.0000000000000247
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© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
COMMENTARY
inclusion of PDT as a first-line treatment option for AC. Furthermore, combination of PDT with adjuvant therapies, such as topical imiquimod at less frequent application, may provide higher cure rates with minimal-tono downtime and lower recurrence rates. In this author’s experience, the subset of AC cases that fail to achieve complete clinical cure after PDT may be treated with adjuvant topical imiquimod twice weekly for 12 to 16 weeks to achieve durable long-term remission (M. Alexiades-Armenakas, unpublished data, 2010). Future research is needed to pursue combination PDT and adjuvant topical therapy approaches to strive toward higher CR and HR rates. In sum, inclusion of PDT as a primary treatment modality for AC is warranted based on the comparable clinical and HRs with minimal side effects, few adverse events, and improved cosmetic outcomes. References 1. Martins-Filho PR, Da Silva LC, Piva MR. The prevalence of actinic cheilitis in farmers in a semi-arid northeastern region of Brazil. Int J Dermatol 2011;50:1109–14. 2. de Oliveira Ribeiro A, da Silva LC, Martins-Filho PR. Prevalence of and risk factors for actinic cheilitis in Brazilian fishermen and women. Int J Dermatol 2014;53:1370–6.
10. Dufresne RG Jr, Curlin MU. Actinic cheilitis: a treatment review. Dermatol Surg 1997;24:490–1. 11. Dinehart SM. The treatment of actinic keratosis. J Am Acad Dermatol 2000;42:25–8. 12. Jadotte YT, Schwartz RA. Solar cheilosis: an ominous precursor. Part II: therapeutic perspectives. J Am Acad Dermatol 2012;66:187–98. 13. Yazdani Abyaneh M, Falto-Aizpurua L, Griffith R, Nouri K. Photodynamic therapy for actinic cheilitis: a systematic review. Dermatol Surg 2015;41:189–98. 14. Robinson JK. Actinic cheilitis. A prospective study comparing four treatment methods. Arch Otolaryngol Head Neck Surg 1989;115: 848–52. 15. Smith KJ, et al. Topical 5% imiquimod for the therapy of actinic cheilitis. J Am Acad Dermatol 2002;47:497–501. 16. McDonald C, Laverick S, Fleming CJ, White SJ. Treatment of actinic cheilitis with imiquimod 5% and a retractor on the lower lip: clinical and histological outcomes in 5 patients. Br J Oral Maxillofac Surg 2010; 48:473–6. 17. Laws RA, Wilde JL, Grabski WJ. Comparison of electrodessication with CO2 laser for the treatment of actinic cheilitis. Dermatol Surg 2000;26: 349–53. 18. Cullen SI. Topical fluorouracil therapy for precancers and cancers of the skin. J Am Geriatr Soc 1979;27:529–35. 19. Greenberg HL, Cohen JL, Rosen T, Orengo I. Severe reaction to 5% imiquimod cream with excellent clinical and cosmetic outcomes. J Drugs Dermatol 2007;6:452–8.
3. Markopoulos A, Albanidou-Farmaki E, Kayavis I. Actinic cheilitis: clinical and pathologic characteristics in 65 cases. Oral Dis 2004;10:212–6.
20. Chakrabarty AK, Mraz S, Geisse JK, Anderson NJ. Aphthous ulcers associated with imiquimod and the treatment of actinic cheilitis. J Am Acad Dermatol 2005;52:35–7.
4. Ochsenius G, Ormeño A, Godoy L, Rojas R. A retrospective study of 232 cases of lip cancer and pre cancer in Chilean patients. Clinicalhistological correlation [in Spanish]. Rev Med Chil 2003;131:60–6.
21. Warnock GR, Fuller RP Jr, Pelleu GB Jr. Evaluation of 5-fluorouracil in the treatment of actinic keratosis of the lip. Oral Surg Oral Med Oral Pathol 1981;52:501–5.
5. Bouquot JE. Oral leukoplakia and erythroplakia: a review and update. Pract Periodontics Aesthet Dent 1994;6:9–17.
22. Epstein E. Treatment of lip keratoses (actinic cheilitis) with topical fluorouracil. Arch Dermatol 1977;113:906–8.
6. Lee JJ, Hong WK, Hittelman WN, Mao L, et al. Predicting cancer development in oral leukoplakia: ten years of translational research. Clin Cancer Res 2000;6:1702–10. 7. Califano L, Zupi A, Massari PS, Giardino C, et al. Lymph-node metastasis in squamous cell carci- noma of the lip. A retrospective analysis of 105 cases. Int J Oral Maxillofac Surg 1994;23:351–5. 8. Zitsch RP, Lee BW, Smith RB. Cervical lymph node metastases and squamous cell carcinoma of the lip. Head Neck 1999;21:447–53.
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9. Altinyollar H, Berberoglu U, Celen O. Lymphatic mapping and sentinel lymph node biopsy in squamous cell carcinoma of the lower lip. Eur J Surg Oncol 2002;28:72–4.
Macrene Alexiades-Armenakas, MD, PhD Yale University School of Medicine New York, New York Dermatology and Laser Surgery Center New York, New York
DERMATOLOGIC SURGERY
© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
the efficacy rates reported in this systematic review of PDT for AC are similar to those reported for other treatment modalities. In assessing relative safety among AC treatments, important advantages to PDT for AC are the excellent side effect profile and cosmetic outcome in contrast to other therapeutic options. Ablative therapies, such as cryotherapy and electrodessication, carry the disadvantages of hypopigmented scarring and long recovery times.10,17 Ablative CO2 laser resurfacing also causes hypopigmented scarring and has a 2-week recovery time.10,17 Topical 5-fluorouracil and imiquimod are associated with severe and unpredictable side effects, including erythema, crusting, ulceration, scarring, and poor cosmetic outcomes.3,10,15,18–22 Treatment of AC with topical 5% imiquimod 3 times per week for 5 to 6 weeks resulted in clearing at 4 weeks of follow-up; however, 60% of patients experienced a moderate-to-severe reaction of erythema, induration, erosions, or ulcerations.15 In extreme cases, surgical treatment with vermilionectomy has been performed but carries a high incidence of scarring and poor cosmetic outcome.10 In contrast, this review reports that patients with AC treated with PDT experienced only transient local reactions and few adverse events, with the primary concern being perioperative pain in a minority of cases treated with methyl aminolevulinic acid and red light PDT. Overall, the review demonstrated few adverse events and excellent post-treatment cosmesis with PDT for AC. Thus, the need for additional treatment options for AC, and the comparable efficacy and superior safety profile associated with PDT for AC that are described in this review, provide a compelling argument for
Supported by research grants from Alma, Syneron, Deka, and Lancome. The author has indicated no significant interest with commercial supporters. © 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2015;41:199–200 DOI: 10.1097/DSS.0000000000000247
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·
199
© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
COMMENTARY
inclusion of PDT as a first-line treatment option for AC. Furthermore, combination of PDT with adjuvant therapies, such as topical imiquimod at less frequent application, may provide higher cure rates with minimal-tono downtime and lower recurrence rates. In this author’s experience, the subset of AC cases that fail to achieve complete clinical cure after PDT may be treated with adjuvant topical imiquimod twice weekly for 12 to 16 weeks to achieve durable long-term remission (M. Alexiades-Armenakas, unpublished data, 2010). Future research is needed to pursue combination PDT and adjuvant topical therapy approaches to strive toward higher CR and HR rates. In sum, inclusion of PDT as a primary treatment modality for AC is warranted based on the comparable clinical and HRs with minimal side effects, few adverse events, and improved cosmetic outcomes. References 1. Martins-Filho PR, Da Silva LC, Piva MR. The prevalence of actinic cheilitis in farmers in a semi-arid northeastern region of Brazil. Int J Dermatol 2011;50:1109–14. 2. de Oliveira Ribeiro A, da Silva LC, Martins-Filho PR. Prevalence of and risk factors for actinic cheilitis in Brazilian fishermen and women. Int J Dermatol 2014;53:1370–6.
10. Dufresne RG Jr, Curlin MU. Actinic cheilitis: a treatment review. Dermatol Surg 1997;24:490–1. 11. Dinehart SM. The treatment of actinic keratosis. J Am Acad Dermatol 2000;42:25–8. 12. Jadotte YT, Schwartz RA. Solar cheilosis: an ominous precursor. Part II: therapeutic perspectives. J Am Acad Dermatol 2012;66:187–98. 13. Yazdani Abyaneh M, Falto-Aizpurua L, Griffith R, Nouri K. Photodynamic therapy for actinic cheilitis: a systematic review. Dermatol Surg 2015;41:189–98. 14. Robinson JK. Actinic cheilitis. A prospective study comparing four treatment methods. Arch Otolaryngol Head Neck Surg 1989;115: 848–52. 15. Smith KJ, et al. Topical 5% imiquimod for the therapy of actinic cheilitis. J Am Acad Dermatol 2002;47:497–501. 16. McDonald C, Laverick S, Fleming CJ, White SJ. Treatment of actinic cheilitis with imiquimod 5% and a retractor on the lower lip: clinical and histological outcomes in 5 patients. Br J Oral Maxillofac Surg 2010; 48:473–6. 17. Laws RA, Wilde JL, Grabski WJ. Comparison of electrodessication with CO2 laser for the treatment of actinic cheilitis. Dermatol Surg 2000;26: 349–53. 18. Cullen SI. Topical fluorouracil therapy for precancers and cancers of the skin. J Am Geriatr Soc 1979;27:529–35. 19. Greenberg HL, Cohen JL, Rosen T, Orengo I. Severe reaction to 5% imiquimod cream with excellent clinical and cosmetic outcomes. J Drugs Dermatol 2007;6:452–8.
3. Markopoulos A, Albanidou-Farmaki E, Kayavis I. Actinic cheilitis: clinical and pathologic characteristics in 65 cases. Oral Dis 2004;10:212–6.
20. Chakrabarty AK, Mraz S, Geisse JK, Anderson NJ. Aphthous ulcers associated with imiquimod and the treatment of actinic cheilitis. J Am Acad Dermatol 2005;52:35–7.
4. Ochsenius G, Ormeño A, Godoy L, Rojas R. A retrospective study of 232 cases of lip cancer and pre cancer in Chilean patients. Clinicalhistological correlation [in Spanish]. Rev Med Chil 2003;131:60–6.
21. Warnock GR, Fuller RP Jr, Pelleu GB Jr. Evaluation of 5-fluorouracil in the treatment of actinic keratosis of the lip. Oral Surg Oral Med Oral Pathol 1981;52:501–5.
5. Bouquot JE. Oral leukoplakia and erythroplakia: a review and update. Pract Periodontics Aesthet Dent 1994;6:9–17.
22. Epstein E. Treatment of lip keratoses (actinic cheilitis) with topical fluorouracil. Arch Dermatol 1977;113:906–8.
6. Lee JJ, Hong WK, Hittelman WN, Mao L, et al. Predicting cancer development in oral leukoplakia: ten years of translational research. Clin Cancer Res 2000;6:1702–10. 7. Califano L, Zupi A, Massari PS, Giardino C, et al. Lymph-node metastasis in squamous cell carci- noma of the lip. A retrospective analysis of 105 cases. Int J Oral Maxillofac Surg 1994;23:351–5. 8. Zitsch RP, Lee BW, Smith RB. Cervical lymph node metastases and squamous cell carcinoma of the lip. Head Neck 1999;21:447–53.
200
9. Altinyollar H, Berberoglu U, Celen O. Lymphatic mapping and sentinel lymph node biopsy in squamous cell carcinoma of the lower lip. Eur J Surg Oncol 2002;28:72–4.
Macrene Alexiades-Armenakas, MD, PhD Yale University School of Medicine New York, New York Dermatology and Laser Surgery Center New York, New York
DERMATOLOGIC SURGERY
© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
