Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2024;14(1):e2024004 1 Combination of Fractional CO2 Laser Therapy and Photodynamic Therapy for the Treatment of Plasma Cell Cheilitis Giulio Cortonesi1, Carolina Donelli1, Corinne Orsini1, Pietro Rubegni1, Emanuele Trovato1 1 Dermatology Section, Department of Medical, Surgical, and Neurological Sciences, Santa Maria Alle Scotte Hospital, Siena, Italy Key words: plasma-cell, cheilitis, laser Citation: Cortonesi G, Donelli C, Rubegni P, Trovato E. Combination of Fractional CO2 Laser Therapy and Photodynamic Therapy for the Treatment of Plasma Cell Cheilitis. Dermatol Pract Concept. 2024;14(1):e2024004. DOI: https://doi.org/10.5826/dpc.1401a4 Accepted: July 6, 2023; Published: January 2024 Copyright: ©2024 Cortonesi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Carolina Donelli, MD, Dermatology Section, Santa Maria Alle Scotte Hospital, Viale Bracci 16, 53100 Siena, Italy. E-mail: carolina.donelli@gmail.com Introduction Plasma cell cheilitis (PCC) is a rare idiopathic inflamma- tory disorder of the oral mucosa characterized by a dense band-like infiltrate of plasma cells in the upper dermis [1,2]. The most common clinical presentation is a slowly evolv- ing, erythematous-violaceous, ulcerated, and asymptomatic plaque of the lower lip. A biopsy with histological examina- tion is generally required to make a differential diagnosis. PCC is not used to resolve spontaneously and it is often re- sistant to topical steroid treatment. The resolution has been documented after systemic or intralesional steroids, systemic griseofulvin, topical calcineurin inhibitors, and destructive measures, including laser therapy [2,3]. Successful therapeu- tic results have been achieved by combining two different therapies that act synergistically [4]. Case Presentation We report the case of a 40-year-old woman, who presented to our dermatology clinic with an ulcerated plaque of the lower lip (Figure 1, A and B), persistent for eighteen months and already histologically diagnosed as plasma cell cheilitis. Since the diagnosis high-potency topical corticosteroid and tacroli- mus 0.03% ointment had been utilized for six months, with no clinical benefit. We decided to try a combined treatment with fractional CO2 laser therapy and photodynamic therapy (PDT). First, under topical anesthesia, the patient underwent a fractional CO2 laser (Smartxide2, DEKA MELA) ablative treatment (power 5 W, scan time 300 ms, spacing 400 µm) and, immediately afterward, methyl aminolevulinate (MAL) 160 mg/g cream was applied on the treated area using an occlusive and nontransparent plastic wrap. Three hours later, the occlusive dressing was removed and the treated skin was exposed to 120 J/cm2 of a red-light source with peak emis- sion at 630 nm (PDT-CLD 100, EPEM) for two minutes. Af- ter therapy, the patient was warned to avoid direct sunlight for the first 36 hours. To promote quick healing, she was advised to apply until complete re-epithelialization a topical non-medicated ointment. Other two cycles of fractional CO2 laser therapy and subsequent PDT were done, after 4 and 8 (Figure 1, C and D) weeks. A follow-up was performed 2 Research Letter | Dermatol Pract Concept. 2024;14(1):e2024004 12 months after the first treatment. The patient reported only mild discomfort related to the red-light exposure after the first treatment cycle, then well controlled by the preventive use of sunscreens. The aesthetic outcome was excellent, without any clinically evident scarring (Figure 1, E and F). Laser-combined therapy is now used to treat lots of diseases [5]. Conclusions Vaporization of intracellular water induced by fractional CO2 laser acts either ablating the abnormal epithelium with good hemostasis of the adjacent structures or favoring pen- etration of the photosensitizer (MAL). The interaction be- tween the photosensitizer and the appropriate activating wavelength of light generates reactive oxygen species causing cell death by necrosis and apoptosis. PDT is able to selec- tively and effectively target the area to treat, with little or no risk of scarring. Such a combined approach is promising because of proven efficacy, minimum associate discomfort, and good aesthetic outcome. Moreover, besides the fact that they are all off-label, the distress associated with using top- ical treatments for long periods is greater. Further studies with wider samples of patients are needed to validate this technique as a therapeutic standard for PCC. References 1. Rocha N, Mota F, Horta M, Lima O, Massa A, Sanches M. Plasma cell cheilitis. J Eur Acad Dermatol Venereol. 2004;18(1):96–98. DOI: 10.1111/j.1468-3083.2004.00791.x. PMID: 14678543. 2. Cohen L, Farahi JM, Brodsky MA, High WA, Hugh J. A Severe Pre- sentation of Plasma Cell Cheilitis. Cutis. 2021;108(2):E28-E31. DOI: 10.12788/cutis.0341. PMID: 34735328. 3. Lugović-Mihić L, Pilipović K, Crnarić I, Šitum M, Duvančić T. Differential Diagnosis of Cheilitis - How to Classify Cheili- tis?.  Acta Clin Croat. 2018;57(2):342-351. DOI: 10.20471 /acc.2018.57.02.16. PMID: 30431729. PMCID: PMC6531998. 4. Yoshimura K, Nakano S, Tsuruta D, Ohata C, Hashimoto T. Suc- cessful treatment with 308-nm monochromatic excimer light and subsequent tacrolimus 0.03% ointment in refractory plasma cell cheilitis. J Dermatol. 2013;40(6):471–474. DOI: 10.1111/1346- 8138.12152. PMID: 23621817. 5. Cortonesi G, Donelli C, Orsini C, Guidi I, Rubegni P, Trovato E. Combination of CO2 laser therapy and pulsed dye laser ther- apy for the treatment of actinic cheilitis. J Cosmet Derma- tol. 2023;22(2):715-716. DOI: 10.1111/jocd.15494. PMID: 36382418. Figure 1. Clinical (A,C,E) and dermoscopic (B,D,F) presentation of the lesion before treatment (A,B), after 8 weeks (C,D) and at 12 months follow-up (E,F).