Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Reviews in Clinical and Experimental Pharmacology
  4. Fast Track Articles
  5. Fast Track Article
image of Effectiveness and Tolerability of Various 5-Fluorouracil Formulations as Adjuvant Therapies for Vitiligo Management: A Systematic Review and Meta-Analysis

Abstract

Background

All vitiligo treatments are restricted, and no known treatment reliably produces repigmentation. In this study, we investigated the efficacy and safety of 5-Fluorouracil (5FU) as adjuvant therapy in treating vitiligo.

Method

Using five significant databases, an electronic systematic search of the literature was conducted. Randomized Clinical Trials (RCTs) that investigated 5FU for treating vitiligo in humans were selected for a meta-analysis and systematic review. This study was conducted by following PROSPERO (CRD42022345736).

Results

A total of 10 studies involving 302 patients were included in our systematic review. The meta-analysis of eight studies revealed that the combination of 5FU with microneedling showed a statistically significant superior effect in comparison with other treatment modalities in inducing >75% repigmentation (OR= 4.47; 95%CI= (2.39, 8.35), < 0.00001). 5FU with microneedling microneedling alone showed higher efficacy of 5FU with statistically significant results (OR= 4.22; 95%CI= (1.55, 11.44), = 0.005). Regarding the influence of different formulations of 5FU, the meta-regression revealed that the highest efficacy was achieved when microneedling was combined with liposomal formulations. There were not any reported severe side effects related to 5FU.

Conclusion

5FU as an adjuvant treatment for vitiligo was found to be more effective in achieving ≥75% repigmentation rates.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/crcep/10.2174/0127724328324817241002112025
2024-10-18
2024-11-26

  • From This Site

    /content/journals/crcep/10.2174/0127724328324817241002112025
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Kemp E.H. Gavalas N.G. Gawkrodger D.J. Weetman A.P. Autoantibody responses to melanocytes in the depigmenting skin disease vitiligo. Autoimmun. Rev. 2007 6 3 138 142 10.1016/j.autrev.2006.09.010 17289548
    [Google Scholar]
  2. Chen J. Li S. Li C. Mechanisms of melanocyte death in vitiligo. Med. Res. Rev. 2021 41 2 1138 1166 10.1002/med.21754 33200838
    [Google Scholar]
  3. Namazi M.R. Neurogenic dysregulation, oxidative stress, autoimmunity, and melanocytorrhagy in vitiligo: can they be interconnected? Pigment Cell Res. 2007 20 5 360 363 10.1111/j.1600‑0749.2007.00408.x 17850509
    [Google Scholar]
  4. Kubelis-López D. Zapata-Salazar N. Said-Fernández S. Sánchez-Domínguez C. Salinas-Santander M. Martínez-Rodríguez H. Vázquez-Martínez O. Wollina U. Lotti T. Ocampo-candiani J. Updates and new medical treatments for vitiligo (Review). Exp. Ther. Med. 2021 22 2 797 10.3892/etm.2021.10229 34093753
    [Google Scholar]
  5. Kanwar A. Kumaran M.S. Childhood vitiligo: Treatment paradigms. Indian J. Dermatol. 2012 57 6 466 474 10.4103/0019‑5154.103067 23248365
    [Google Scholar]
  6. Abdelwahab M. Salah M. Samy N. Rabie A. Farrag A.R. Effect of topical 5-fluorouracil alone versus its combination with erbium:Yag (2940 nm) laser in treatment of vitiligo. Clin. Cosmet. Investig. Dermatol. 2020 13 77 85 10.2147/CCID.S225881 32021372
    [Google Scholar]
  7. Jain S. Puri R. Development, characterization and in vivo localization study of topical 5-fluorouracil gels: a comparative study with conventional formulation. Curr. Drug Deliv. 2014 11 3 401 414 10.2174/1567201810666131210112150 24328603
    [Google Scholar]
  8. Mura S. Bui D.T. Couvreur P. Nicolas J. Lipid prodrug nanocarriers in cancer therapy. J. Control. Release 2015 208 25 41 10.1016/j.jconrel.2015.01.021 25617724
    [Google Scholar]
  9. Dillon A.B. Sideris A. Hadi A. Elbuluk N. Advances in vitiligo: An update on medical and surgical treatments. J. Clin. Aesthet. Dermatol. 2017 10 1 15 28 28210378
    [Google Scholar]
  10. Liberati A. Altman D.G. Tetzlaff J. Mulrow C. Gøtzsche P.C. Ioannidis J.P.A. Clarke M. Devereaux P.J. Kleijnen J. Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009 6 7 e1000100 10.1371/journal.pmed.1000100 19621070
    [Google Scholar]
  11. The social care guidance manual. 2016 Available from:https://www.nice.org.uk/process/pmg10/chapter/appendix-b-methodology-checklist-systematic-reviews-and-meta-analyses(accessed on 21-9-2024)
  12. Nofal A. Eldeeb F. Shalaby M. Al-Balat W. Microneedling combined with pimecrolimus, 5‐fluorouracil, and trichloroacetic acid in the treatment of vitiligo: A comparative study. Dermatol. Ther. 2022 35 3 e15294 10.1111/dth.15294 34964230
    [Google Scholar]
  13. Ghiya B.C. Soni P. Singrodia A. Chhabra S. Mehta R.D. Bai J. Comparative evaluation of the therapeutic efficacy of microneedling alone or microneedling combined with topical 5-fluorouracil in localized stable childhood vitiligo. Advances in Human Biology 2016 6 1 25 28 [AHB]. 10.4103/2321‑8568.190142
    [Google Scholar]
  14. Collaboration T.C. Review Manager (RevMan). 2020 Available from: https://community.cochrane.org/book_pdf/1416(accessed on 21-9-2024)
  15. Wallace B.C. Dahabreh I.J. Trikalinos T.A. Lau J. Trow P. Schmid C.H. Closing the gap between methodologists and end-users: R as a computational back-end. J. Stat. Softw. 2012 49 5 1 15 10.18637/jss.v049.i05
    [Google Scholar]
  16. Haddaway N.R. Page M.J. Pritchard C.C. McGuinness L.A. PRISMA2020 : An R package and Shiny app for producing PRISMA 2020‐compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Syst. Rev. 2022 18 2 e1230 10.1002/cl2.1230 36911350
    [Google Scholar]
  17. Arora S. Agrawal O. Malhotra S. Saini R. Neki N. Dermabration followed by topical 5% 5-fluorouracil and autologous melanocyte transplantation in stable vitiligo. Int. j. curr. med. pharm. res. 2018 4 3091 3095
    [Google Scholar]
  18. Asilian A. Kazemipour S. Mokhtari F. Iraji F. Shahmoradi Z. Mohaghegh F. Mozafarpoor S. Talakoub M. Effectiveness of dermabrasion plus 5‐fluorouracil vs suction blister in treating vitiligo: A comparative study. Dermatol. Ther. 2021 34 2 e14750 10.1111/dth.14750 33403790
    [Google Scholar]
  19. Attwa E.M. Khashaba S.A. Ezzat N.A. Evaluation of the additional effect of topical 5‐fluorouracil to needling in the treatment of localized vitiligo. J. Cosmet. Dermatol. 2020 19 6 1473 1478 10.1111/jocd.13152 31524967
    [Google Scholar]
  20. Jartarkar S. Manjunath K. Harini S. Sampath S. A single blind active controlled study to compare the efficacy of microneedling and microneedling with 5-flurouracil in treatment of stable vitiligo. Przegl. Dermatol. 2021 108 4 275 284 10.5114/dr.2021.111306
    [Google Scholar]
  21. Mina M. Elgarhy L. Al-saeid H. Ibrahim Z. Comparison between the efficacy of microneedling combined with 5‐fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo. J. Cosmet. Dermatol. 2018 17 5 744 751 10.1111/jocd.12440 29532621
    [Google Scholar]
  22. Matharoo P. Sharma S. Kaur J. Bassi R. Comparison of the efficacy of microneedling combined with 5-fluorouracil 5% cream versus microneedling combined with tacrolimus 0.1% ointment in the treatment of vitiligo. Deri Hastalik. Frengi Arsivi 2022 56 2 64 69 10.4274/turkderm.galenos.2022.57804
    [Google Scholar]
  23. Aliabadi A. Sabourirad S. Vahabi-Amlashi S. Jaafari M.R. Hadianfar A. Comparison of two therapeutic modalities of microneedling alone and with 5-fluorouracil in treatment of resistant vitiligo lesions. Majallah-i Danishkadah-i Pizishki-i Isfahan 2021 39 617 624
    [Google Scholar]
  24. Pazyar N. Hatami M. Yaghoobi R. Parvar S.Y. Radmanesh M. Hadibarhaghtalab M. The efficacy of adding topical 5‐fluorouracil to micro‐needling in the treatment of vitiligo: A randomized controlled trial. J. Cosmet. Dermatol. 2023 22 5 1513 1520 10.1111/jocd.15616 36718813
    [Google Scholar]
  25. Makki M.A. Saudi W. Hasan H. Carbon dioxide laser-assisted dermabrasion versus mechanical dermabrasion in the treatment of stable vitiligo. J. Egypt. Womens Dermatol. Soc. 2019 16 3 179 183 10.4103/JEWD.JEWD_22_19
    [Google Scholar]
  26. Galal S. Ali M. Elzeiny F. Evaluation of efficacy and safety topical 5-fluorouracil 0.5% in treatment of resistant vitiligo [alone or after microneedling]; a pilot study. Int. J. Med. Arts 2021 3 4 1803 1810 [IJMA]. 10.21608/ijma.2021.89242.1347
    [Google Scholar]
  27. Abd El-Samad Z. Shaaban D. Treatment of localized non-segmental vitiligo with intradermal 5-flurouracil injection combined with narrow-band ultraviolet B: A preliminary study. J. Dermatolog. Treat. 2012 23 6 443 448 10.3109/09546634.2011.579084 21781011
    [Google Scholar]
  28. Elgarhy L.H. El-Tatawy R.A. Ali D.M. Anber D.M. Iskandarani Y.A. Ismail M.A. Treatment of stable nonsegmental vitiligo using transdermal delivery of 5‐fluorouracil by fractional CO 2 laser versus intralesional injection of 5‐fluorouracil, both followed by narrow‐band type ultraviolet B (UVB): A comparative study. J. Cosmet. Dermatol. 2022 21 9 3832 3841 10.1111/jocd.14691 35005831
    [Google Scholar]
  29. Doghaim N.N. El-Tatawy R.A. Ismail M.A. Ali D.A.M. El Attar Y.A. Study the effect of erbium:YAG laser plus topical 5‐flurouracil in stable vitiligo resistant to NB‐UVB phototherapy. J. Cosmet. Dermatol. 2020 19 1 122 130 10.1111/jocd.13134 31571367
    [Google Scholar]
  30. Saad M.A. Tawfik K.M. Abdelaleem H.L. Efficacy and safety of micro‐needling combined with topical 5‐fluorouracil and excimer light vs. excimer light alone in treatment of non‐segmental vitiligo: A comparative study. J. Cosmet. Dermatol. 2023 22 3 810 821 10.1111/jocd.15481 36343160
    [Google Scholar]
  31. Speeckaert R. van Geel N. Vitiligo: An Update on Pathophysiology and Treatment Options. Am. J. Clin. Dermatol. 2017 18 6 733 744 10.1007/s40257‑017‑0298‑5 28577207
    [Google Scholar]
  32. Adil M. Zahra F.T. Amin S. Mohtashim M. Bansal R. Khan H. Efficacy of topical 5% 5-fluorouracil with needling versus 5% 5-fluorouracil alone in stable vitiligo: A randomized controlled study. J. Cutan. Aesthet. Surg. 2020 13 3 197 203 10.4103/JCAS.JCAS_12_20 33208995
    [Google Scholar]
  33. Gauthier Y. Anbar T. Lepreux S. Cario-André M. Benzekri L. Possible mechanisms by which topical 5-Fluorouracil and dermabrasion could induce pigment spread in vitiligo skin: an experimental study. ISRN Dermatol. 2013 2013 1 7 10.1155/2013/852497 23691347
    [Google Scholar]
  34. Taieb A. Alomar A. Böhm M. Dell’Anna M.L. De Pase A. Eleftheriadou V. Ezzedine K. Gauthier Y. Gawkrodger D.J. Jouary T. Leone G. Moretti S. Nieuweboer-Krobotova L. Olsson M.J. Parsad D. Passeron T. Tanew A. van der Veen W. van Geel N. Whitton M. Wolkerstorfer A. Picardo M. Vitiligo European Task Force (VETF) European Academy of Dermatology and Venereology (EADV) Union Europe´enne des Me´decins Spe´cialistes (UEMS) Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br. J. Dermatol. 2013 168 1 5 19 10.1111/j.1365‑2133.2012.11197.x 22860621
    [Google Scholar]
  35. Luger T. Paul C. Potential new indications of topical calcineurin inhibitors. Dermatology 2007 215 Suppl. 1 45 54 10.1159/000102119 18174692
    [Google Scholar]
  36. Al-Daraji W.I. Grant K.R. Ryan K. Saxton A. Reynolds N.J. Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporin A. J. Invest. Dermatol. 2002 118 5 779 788 10.1046/j.1523‑1747.2002.01709.x 11982754
    [Google Scholar]
  37. Khandpur S. Khanna U. What is new in narrow-band ultraviolet-B therapy for vitiligo? Indian Dermatol. Online J. 2019 10 3 234 243 10.4103/idoj.IDOJ_310_18 31149564
    [Google Scholar]
  38. Esmat S. Hegazy R.A. Shalaby S. Chu-Sung Hu S. Lan C.C.E. Phototherapy and combination therapies for vitiligo. Dermatol. Clin. 2017 35 2 171 192 10.1016/j.det.2016.11.008 28317527
    [Google Scholar]
  39. Liebl H. Kloth L.C. Skin cell proliferation stimulated by microneedles. J. Am. Coll. Clin. Wound Spec. 2012 4 1 2 6 10.1016/j.jccw.2012.11.001 24527373
    [Google Scholar]
  40. Donnelly R.F. Singh T.R.R. Woolfson A.D. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety. Drug Deliv. 2010 17 4 187 207 10.3109/10717541003667798 20297904
    [Google Scholar]
  41. Qu F. Geng R. Liu Y. Zhu J. Advanced nanocarrier- and microneedle-based transdermal drug delivery strategies for skin diseases treatment. Theranostics 2022 12 7 3372 3406 10.7150/thno.69999 35547773
    [Google Scholar]
  42. Ali M. Namjoshi S. Benson H.A.E. Mohammed Y. Kumeria T. Dissolvable polymer microneedles for drug delivery and diagnostics. J. Control. Release 2022 347 561 589 10.1016/j.jconrel.2022.04.043 35525331
    [Google Scholar]
  43. Sethi S. Mahajan B.B. Gupta R.R. Ohri A. Comparative evaluation of the therapeutic efficacy of dermabrasion, dermabrasion combined with topical 5% 5‐fluorouracil cream, and dermabrasion combined with topical placentrex gel in localized stable vitiligo. Int. J. Dermatol. 2007 46 8 875 879 10.1111/j.1365‑4632.2007.03226.x 17651178
    [Google Scholar]
  44. El Mofty M. Esmat S. Hunter N. Mashaly H.M. Dorgham D. Shaker O. Ibrahim S. Effect of different types of therapeutic trauma on vitiligo lesions. Dermatol. Ther. 2017 30 2 e12447 10.1111/dth.12447 27998025
    [Google Scholar]
  45. Alkilani A. McCrudden M.T. Donnelly R. Transdermal drug delivery: Innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics 2015 7 4 438 470 10.3390/pharmaceutics7040438 26506371
    [Google Scholar]
  46. Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation. 2018 Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/liposome-drug-products-chemistry-manufacturing-and-controls-human-pharmacokinetics-and(accessed on 21-9-2024)
  47. Nsairat H. Khater D. Sayed U. Odeh F. Al Bawab A. Alshaer W. Liposomes: structure, composition, types, and clinical applications. Heliyon 2022 8 5 e09394 10.1016/j.heliyon.2022.e09394 35600452
    [Google Scholar]
  48. El Maghraby G.M. Barry B.W. Williams A.C. Liposomes and skin: From drug delivery to model membranes. Eur. J. Pharm. Sci. 2008 34 4-5 203 222 10.1016/j.ejps.2008.05.002 18572392
    [Google Scholar]
  49. Kalyane D. Raval N. Maheshwari R. Tambe V. Kalia K. Tekade R.K. Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Mater. Sci. Eng. C 2019 98 1252 1276 10.1016/j.msec.2019.01.066 30813007
    [Google Scholar]
  50. Liu P. Chen G. Zhang J. A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules 2022 27 4 1372 10.3390/molecules27041372 35209162
    [Google Scholar]
  51. Haque T. Talukder M.M.U. Chemical enhancer: A simplistic way to modulate barrier function of the stratum corneum. Adv. Pharm. Bull. 2018 8 2 169 179 10.15171/apb.2018.021 30023318
    [Google Scholar]
  52. Vasudevan D.T. Rajan R. Effect of permeation enhancers on the penetration mechanism of transfersomal gel of ketoconazole. J. Adv. Pharm. Technol. Res. 2012 3 2 112 116 10.4103/2231‑4040.97286 22837959
    [Google Scholar]
  53. Zohdy H.A.E.W. Hussein M.S. Intradermal injection of Fluorouracil versus triamcinolone in localized vitiligo treatment. J. Cosmet. Dermatol. 2019 18 5 1430 1434 10.1111/jocd.12820 30444065
    [Google Scholar]
/content/journals/crcep/10.2174/0127724328324817241002112025
Loading
Effectiveness and Tolerability of Various 5-Fluorouracil Formulations as Adjuvant Therapies for Vitiligo Management: A Systematic Review and Meta-Analysis
Bentham Science Publishers ; https://doi.org/10.2174/0127724328324817241002112025
/content/journals/crcep/10.2174/0127724328324817241002112025
/content/journals/crcep/10.2174/0127724328324817241002112025
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: adjuvant ; systematic review ; Meta-analysis ; 5FU ; vitiligo

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test