Antimicrobial photodynamic therapy in herpes labialis pain relief: a comprehensive systematic review

Autores/as

DOI:

https://doi.org/10.5327/2525-5711.298

Palabras clave:

Herpes labialis, Photochemotherapy, Herpes simplex, Systematic review

Resumen

Introduction: Herpes labialis, caused by the herpes simplex virus (HSV), leads to painful lesions around the lips. Current treatments primarily consist of topic antiviral agents, which often fail to provide immediate pain relief. Antimicrobial photodynamic therapy (aPDT) has emerged as a potential adjunctive treatment, but its effectiveness in reducing pain associated with herpes labialis remains unclear. Objective: This study aimed to evaluate the effectiveness of aPDT as an adjunctive treatment for reducing pain in herpes labialis. Methods: A systematic review was conducted following PRISMA guidelines and registered in the PROSPERO database (CRD42023474979). The review addressed the PICO question: Is aPDT effective in reducing pain compared to topic antiviral treatment alone? Electronic searches were conducted in PubMed/MEDLINE, Cochrane Library, and Web of Science for studies published until October 2024. Eligible studies were randomized controlled trials (RCTs) published in English that compared aPDT with antiviral agents. Results: Of the 184 articles identified, two studies involving 120 patients were selected for qualitative analysis. The findings indicated that aPDT, when used alongside topic antivirals, effectively reduced pain symptoms in herpes labialis compared to antiviral treatment alone. However, due to the limited number of studies and variability in outcome measures, the evidence remains preliminary. Conclusion: Based on this review, the use of aPDT as an adjunct to topical antiviral treatment appears to reduce pain symptoms associated with herpes labialis lesions compared to antiviral treatment alone. However, due to the limited number of randomized clinical trials and variability in the results, further research is necessary to establish standardized guidelines for its use.

Citas

Higgins CR, Schofield JK, Tatnall FM, Leigh IM. Natural history, management and complications of herpes labialis. J Med Virol. 1993;Suppl 1:22-6. https://doi.org/10.1002/jmv.1890410506

Herpes simplex – Pipeline insight, 2024. Research and markets [Internet]. [cited 2025 Apr 6]. Available from: https://www.researchandmarkets.com/reports/5510460/herpes-simplex-pipeline-insight-2024

Spruance SL. Pathogenesis of herpes simplex labialis: excretion of virus in the oral cavity. J Clin Microbiol. 1984;19(5):675-9. https://doi.org/10.1128/jcm.19.5.675-679.1984

Petti S, Lodi G. The controversial natural history of oral herpes simplex virus type 1 infection. Oral Dis. 2019;25(8):1850-65. https://doi.org/10.1111/odi.13234

Spruance SL. The natural history of recurrent oral-facial herpes simplex virus infection. Semin Dermatol. 1992;11(3):200-6. PMID: 1390034.

Rytel MW, Niebojewski RA, Aguilar-Torres FG, Russell TJ. Recurrent herpes simplex labialis: viral replication and clinical course. Am J Med Sci. 1978;276(3):319-23. https://doi.org/10.1097/00000441-197811000-00009

Arduino PG, Porter SR. Herpes simplex virus type 1 infection: overview on relevant clinico-pathological features. J Oral Pathol Med. 2008;37(2):107-21. https://doi.org/10.1111/j.1600-0714.2007.00586.x

Gopinath D, Koe KH, Maharajan MK, Panda S. A comprehensive overview of epidemiology, pathogenesis and the management of herpes labialis. Viruses. 2023;15(1):225. https://doi.org/10.3390/v15010225

Boes H, Goulioumis V, Wechsler A, Zimmer S, Bizhang M. Clinical study on the effectiveness of three products in the treatment of herpes simplex labialis. Sci Rep. 2020;10(1):6465. https://doi.org/10.1038/s41598-020-63530-6

Woo SB, Challacombe SJ. Management of recurrent oral herpes simplex infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103 Suppl:S12.e1-18. https://doi.org/10.1016/j.tripleo.2006.11.004

Raborn GW, Grace MGA. Recurrent herpes simplex labialis: selected therapeutic options. J Can Dent Assoc. 2003;69(8):498-503. PMID: 12954137.

Spruance SL, Freeman DJ. Topical treatment of cutaneous herpes simplex virus infections. Antiviral Res. 1990;14(6):305-21. https://doi.org/10.1016/0166-3542(90)90050-h

Spruance SL, Stewart JC, Rowe NH, McKeough MB, Wenerstrom G, Freeman DJ. Treatment of recurrent herpes simplex labialis with oral acyclovir. J Infect Dis. 1990;161(2):185-90. https://doi.org/10.1093/infdis/161.2.185

Yeo JM, Fiddian AP. Acyclovir in the management of herpes labialis. J Antimicrob Chemother. 1983;12 Suppl B:95-103. https://doi.org/10.1093/jac/12.suppl_b.95

Hull CM, Brunton S. The role of topical 5% acyclovir and 1% hydrocortisone cream (XereseTM) in the treatment of recurrent herpes simplex labialis. Postgrad Med. 2010;122(5):1-6. https://doi.org/10.3810/pgm.2010.09.2216

Rechenchoski DZ, Faccin-Galhardi LC, Linhares REC, Nozawa C. Herpesvirus: an underestimated virus. Folia Microbiol (Praha). 2017;62(2):151-6. https://doi.org/10.1007/s12223-016-0482-7

Álvarez DM, Castillo E, Duarte LF, Arriagada J, Corrales N, Farías MA, et al. Current antivirals and novel botanical molecules interfering with herpes simplex virus infection. Front Microbiol. 2020;11:139. https://doi.org/10.3389/fmicb.2020.00139

Silva-Alvarez AF, Carvalho ACW, Benassi-Zanqueta E, Oliveira TZ, Fonseca DP, Ferreira MP, et al. Herpes labialis: a new possibility for topical treatment with well-elucidated drugs. J Pharm Sci. 2021;110(10):3450-6. https://doi.org/10.1016/j.xphs.2021.06.029

Zanella PA, Onuchic LF, Watanabe EH, Azevedo LH, Aranha ACC, Ramalho KM, et al. Photobiomodulation for preventive therapy of recurrent herpes labialis: a 2-year in vivo randomized controlled study. Photobiomodul Photomed Laser Surg. 2022;40(10):682-90. https://doi.org/10.1089/photob.2022.0054

Merigo E, Rocca JP, Pinheiro ALB, Fornaine C. Photobiomodulation therapy in oral medicine: a guide for the practitioner with focus on new possible protocols. Photobiomodul Photomed Laser Surg. 2019;37(11):669-80. https://doi.org/10.1089/photob.2019.4624

Jagdeo J, Austin E, Mamalis A, Wong C, Ho D, Siegel DM. Light-emitting diodes in dermatology: A systematic review of randomized controlled trials. Lasers Surg Med. 2018;50(6):613-28. https://doi.org/10.1002/lsm.22791

Lago ADN, Fortes ABC, Furtado GS, Menezes CFS, Gonçalves LM. Association of antimicrobial photodynamic therapy and photobiomodulation for herpes simplex labialis resolution: case series. Photodiagnosis Photodyn Ther. 2020;32:102070. https://doi.org/10.1016/j.pdpdt.2020.102070

Wainwright M. Local treatment of viral disease using photodynamic therapy. Int J Antimicrob Agents. 2003;21(6):510-20. https://doi.org/10.1016/s0924-8579(03)00035-9

Wainwright M, Maisch T, Nonell S, Plaetzer K, Almeida A, Tegos GP, et al. Photoantimicrobials-are we afraid of the light? Lancet Infect Dis. 2017;17(2):e49-e55. https://doi.org/10.1016/S1473-3099(16)30268-7

Wainwright M, Antczak J, Baca M, Loughran C, Meegan K. Phenothiazinium photoantimicrobials with basic side chains. J Photochem Photobiol B. 2015;150:38-43. https://doi.org/10.1016/j.jphotobiol.2014.12.017

Wainwright M, McLean A. Rational design of phenothiazinium derivatives and photoantimicrobial drug discovery. Dyes Pigm. 2017;136:590-600. https://doi.org/10.1016/j.dyepig.2016.09.015

Shibli JA, Brugnera Junior A, Theodoro LH. Antimicrobial photodynamic therapy for the treatment of periodontitis and peri-implantitis: what are we missing? Photobiomodul Photomed Laser Surg. 2021;39(8):502-3. https://doi.org/10.1089/photob.2021.0067

Lotufo MA, Horliana ACRT, Santana T, Queiroz AC, Gomes AO, Motta LJ, et al. Efficacy of photodynamic therapy on the treatment of herpes labialis: a systematic review. Photodiagnosis Photodyn Ther. 2020;29:101536. https://doi.org/10.1016/j.pdpdt.2019.08.018

Khalil M, Hamadah O. Association of photodynamic therapy and photobiomodulation as a promising treatment of herpes labialis: a systematic review. Photobiomodul Photomed Laser Surg. 2022;40(5):299-307. https://doi.org/10.1089/photob.2021.0186

Al-Maweri SA, Kalakonda B, AlAizari NA, Al-Soneidar WA, Ashraf S, Abdulrab S, et al. Efficacy of low-level laser therapy in management of recurrent herpes labialis: a systematic review. Lasers Med Sci. 2018;33(7):1423-30. https://doi.org/10.1007/s10103-018-2542-5

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023) [Internet]. Cochrane; 2023 [accessed in Nov. 12, 2023]. Available from: https://training.cochrane.org/handbook

Ajmal M. Effectiveness of photodynamic therapy as an adjunct to topical antiviral therapy in the treatment of herpes labialis: a randomized controlled clinical trial. Photodiagnosis Photodyn Ther. 2021;34:102302. https://doi.org/10.1016/j.pdpdt.2021.102302

Ramalho KM, Cunha SR, Gonçalves F, Escudeiro GS, Steiner-Oliveira C, Horliana ACRT, et al. Photodynamic therapy and Acyclovir in the treatment of recurrent herpes labialis: a controlled randomized clinical trial. Photodiagnosis Photodyn Ther. 2021;33:102093. https://doi.org/10.1016/j.pdpdt.2020.102093

Lin HS, Lin PT, Tsai YS, Chi CC. Interventions for treatment of herpes labialis (cold sores on the lips). Cochrane Database Syst Rev. 2022;2022(12):CD015216. https://doi.org/10.1002/14651858.CD015216

Adams AJ, Klepser ME. Pharmacy-based assessment and management of herpes labialis (cold sores) with antiviral therapy. Innov Pharm. 2020;11(3):10.24926/iip.v11i3.1532. https://doi.org/10.24926/iip.v11i3.1532

Sharma D, Sharma S, Akojwar N, Dondulkar A, Yenorkar N, Pandita D, et al. An insight into current treatment strategies, their limitations, and ongoing developments in vaccine technologies against herpes simplex infections. Vaccines (Basel). 2023;11(2):206. https://doi.org/10.3390/vaccines11020206

Menendez CM, Carr DJJ. Defining nervous system susceptibility during acute and latent herpes simplex virus-1 infection. J Neuroimmunol. 2017;308:43-9. https://doi.org/10.1016/j.jneuroim.2017.02.020

Kłysik K, Pietraszek A, Karewicz A, Nowakowska M. Acyclovir in the treatment of herpes viruses-a review. Curr Med Chem. 2020;27(24):4118-37. https://doi.org/10.2174/0929867325666180309105519

Ghorbani J, Rahban D, Aghamiri S, Teymouri A, Bahador A. Photosensitizers in antibacterial photodynamic therapy: an overview. Laser Ther. 2018;27(4):293-302. https://doi.org/10.5978/islsm.27_18-RA-01

Marotti J, Aranha ACC, Eduardo CP, Ribeiro MS. Photodynamic therapy can be effective as a treatment for herpes simplex labialis. Photomed Laser Surg. 2009;27(2):357-63. https://doi.org/10.1089/pho.2008.2268

Namvar MA, Vahedi M, Abdolsamadi HR, Mirzaei A, Mohammadi Y, Jalilian FA. Effect of photodynamic therapy by 810 and 940 nm diode laser on Herpes Simplex Virus 1: an in vitro study. Photodiagnosis Photodyn Ther. 2019;25:87-91. https://doi.org/10.1016/j.pdpdt.2018.11.011

Bacon TH, Levin MJ, Leary JJ, Sarisky RT, Sutton D. Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy. Clin Microbiol Rev. 2003;16(1):114-28. https://doi.org/10.1128/CMR.16.1.114-128.2003

La Selva A, Negreiros RM, Bezerra DT, Rosa EP, Pavesi VCS, Navarro RS, et al. Treatment of herpes labialis by photodynamic therapy: study protocol clinical trial (SPIRIT compliant). Medicine (Baltimore). 2020;99(12):e19500. https://doi.org/10.1097/MD.0000000000019500

Brennan MJ. The clinical implications of cytochrome p450 interactions with opioids and strategies for pain management. J Pain Symptom Manage. 2012;44(6 Suppl):S15-22. https://doi.org/10.1016/j.jpainsymman.2012.08.012

Furtado GS, Paschoal MAB, Grenho LCS, Lago ADN. Does pre-irradiation time influence the efficacy of antimicrobial photodynamic therapy? Photodiagnosis Photodyn Ther. 2020;31:101884. https://doi.org/10.1016/j.pdpdt.2020.101884

Carrera ET, Dias HB, Corbi SCT, Marcantonio RAC, Bernardi ACA, Bagnato VS, et al. The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review. Laser Phys. 2016;26(12):123001. https://doi.org/10.1088/1054-660X/26/12/123001

Opstelten W, Neven AK, Eekhof J. Treatment and prevention of herpes labialis. Can Fam Physician. 2008;54(12):1683-7. PMID: 19074705.

Fumes AC, Romualdo PC, Monteiro RM, Watanabe E, Corona SAM, Borsatto MC. Influence of pre-irradiation time employed in antimicrobial photodynamic therapy with diode laser. Lasers Med Sci. 2018;33(1):67-73. https://doi.org/10.1007/s10103-017-2336-1

Lago ADN, Fortes ABC, Furtado GS, Menezes CFS, Gonçalves LM. Association of antimicrobial photodynamic therapy and photobiomodulation for herpes simplex labialis resolution: case series. Photodiagnosis Photodyn Ther. 2020;32:102070. https://doi.org/10.1016/j.pdpdt.2020.102070

Rezende SB, Campos L, Palma LF, Tateno RY, Simões A, Macedo MC, et al. Antimicrobial photodynamic therapy for recurrent herpes labialis in chronic graft-versus-host disease: a case report. Photodermatol Photoimmunol Photomed. 2021;37(4):321-3. https://doi.org/10.1111/phpp.12655

Patel JJ, Hill A, Lee ZY, Heyland DK, Stoppe C. Critical appraisal of a systematic review: a concise review. Crit Care Med. 2022;50(9):1371-9. https://doi.org/10.1097/CCM.0000000000005602

Publicado

2025-06-17

Cómo citar

1.
Santana AP, Mulinari-Santos G, Assunção WG, Garcia VG, Theodoro LH. Antimicrobial photodynamic therapy in herpes labialis pain relief: a comprehensive systematic review. J Oral Diagn [Internet]. 17 de junio de 2025 [citado 18 de junio de 2025];10. Disponible en: https://www.joraldiagnosis.com/revista/article/view/298

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Sección

Review Article