Efficacy of Intralesional Candida Injection in the Treatment of Cutaneous Warts: A Systematic Review and Meta-Analysis

Authors

  • Chin-Hsuan Chang School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • Zih-Yi Sung School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • Yu-Chen Huang Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

DOI:

https://doi.org/10.2340/actadv.v104.40819

Keywords:

Warts, Verruca, Immunotherapy, Candida, Meta-analysis

Abstract

Recent studies that examined the treatment efficacy of Candida antigen injection for both non-genital and genital warts yield inconsistent results. To address this, a systematic review and meta-analysis was conducted, comparing the treatment response between Candida antigen injection therapy and other intralesional immunotherapies across all types of warts. PubMed, Cochrane Library, and Embase were searched for relevant randomized controlled trials (RCTs) from inception to 16 September 2023, and 24 eligible RCTs were identified. A protocol was developed using the PRISM A-P checklist. In terms of complete clearance, intralesional Candida injection therapy demonstrated a significant improvement compared with saline (risk ratio [RR] 5.39; 95% confidence interval [CI] 3.49–8.33; I2=0%). However, no statistically significant differences were observed when compared with other therapies such as mumps–measles–rubella vaccines, purified protein derivative, vitamin D3, bivalent human papillomavirus vaccine, and zinc sulphate. Adverse effects associated with intralesional Candida therapy were generally reported as mild and manageable. In conclusion, intralesional Candida injection therapy for cutaneous warts may exhibit a superior complete and distant response rate. Nevertheless, owing to a limited sample size and other limitations, future research should aim for larger studies to provide more conclusive evidence.

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References

Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, et al. Global burden of human papillomavirus and related diseases. Vaccine 2012; 30 Suppl 5: F12-23.

https://doi.org/10.1016/j.vaccine.2012.07.055 DOI: https://doi.org/10.1016/j.vaccine.2012.07.055

Friedman PC. Management of difficult-to-treat warts: traditional and new approaches. Am J Clin Dermatol 2021; 22: 379-394.

https://doi.org/10.1007/s40257-020-00582-4 DOI: https://doi.org/10.1007/s40257-020-00582-4

Khozeimeh F, Jabbari Azad F, Mahboubi Oskouei Y, Jafari M, Tehranian S, Alizadehsani R, et al. Intralesional immunotherapy compared to cryotherapy in the treatment of warts. Int J Dermatol 2017; 56: 474-478.

https://doi.org/10.1111/ijd.13535 DOI: https://doi.org/10.1111/ijd.13535

Majid I, Imran S. Immunotherapy with intralesional Candida albicans antigen in resistant or recurrent warts: a study. Indian J Dermatol 2013; 58: 360-365.

https://doi.org/10.4103/0019-5154.117301 DOI: https://doi.org/10.4103/0019-5154.117301

Fawzy MM, Nofal A, Alakad R. Intralesional antigen immunotherapy for the treatment of plane warts: a comparative study. Dermatol Ther 2020; 33: e13807.

https://doi.org/10.1111/dth.13807 DOI: https://doi.org/10.1111/dth.13807

Salman S, Ahmed MS, Ibrahim AM, Mattar OM, El-Shirbiny H, Sarsik S, et al. Intralesional immunotherapy for the treatment of warts: a network meta-analysis. J Am Acad Dermatol 2019; 80: 922-930.e924.

https://doi.org/10.1016/j.jaad.2018.07.003 DOI: https://doi.org/10.1016/j.jaad.2018.07.003

Ju HJ, Park HR, Kim JY, Kim GM, Bae JM, Lee JH. Intralesional immunotherapy for non-genital warts: a systematic review and meta-analysis. Indian J Dermatol Venereol Leprol 2022; 88: 724-737.

https://doi.org/10.25259/IJDVL_1369_20 DOI: https://doi.org/10.25259/IJDVL_1369_20

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097.

https://doi.org/10.1371/journal.pmed.1000097 DOI: https://doi.org/10.1371/journal.pmed.1000097

Furlan JC, Singh J, Hsieh J, Fehlings MG. Methodology of systematic reviews and recommendations. J Neurotrauma 2011; 28: 1335-1339.

https://doi.org/10.1089/neu.2009.1146 DOI: https://doi.org/10.1089/neu.2009.1146

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560.

https://doi.org/10.1136/bmj.327.7414.557 DOI: https://doi.org/10.1136/bmj.327.7414.557

Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56: 455-463.

https://doi.org/10.1111/j.0006-341X.2000.00455.x DOI: https://doi.org/10.1111/j.0006-341X.2000.00455.x

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634.

https://doi.org/10.1136/bmj.315.7109.629 DOI: https://doi.org/10.1136/bmj.315.7109.629

Abdel Razik LH, Obaid ZM, Fouda I. Intralesional Candida antigen versus intralesional vitamin D3 in the treatment of recalcitrant multiple common warts. J Cosmet Dermatol 2021; 20: 3341-3346.

https://doi.org/10.1111/jocd.14335 DOI: https://doi.org/10.1111/jocd.14335

Abdelaal MA, Abdelaziz HM, Ahmed KA, Elsaie ML. Comparative study of intralesional vitamin D3 injection and candida albicans antigen in treating plantar warts. J Drug Dermatol 2021; 20: 546-549.

Amer A, Nassar A, Gamal D, Marei A. Effect of varicella zoster vaccine vs candida antigen injection in treatment of warts. Dermatol Ther 2021; 34: e14667.

https://doi.org/10.1111/dth.14667 DOI: https://doi.org/10.1111/dth.14667

Chaudhary M, Brar A, Agarwal P, Chavda V, Jagati A, Rathod SP. A study of comparison and evaluation of various intralesional therapies in cutaneous warts. Indian Dermatol Online J 2023; 14: 487-492.

https://doi.org/10.4103/idoj.idoj_492_22 DOI: https://doi.org/10.4103/idoj.idoj_492_22

Eldahshan RM, Ashry WMO, Elsaie ML. Comparative study between intralesional injection of MMR, BCG, and candida albicans antigen in treatment of multiple recalcitrant warts. J Cosmet Dermatol 2022; 21: 1120-1126.

https://doi.org/10.1111/jocd.14737 DOI: https://doi.org/10.1111/jocd.14737

Fathy G, Sharara MA, Khafagy AH. Intralesional vitamin D3 versus Candida antigen immunotherapy in the treatment of multiple recalcitrant plantar warts: a comparative case-control study. Dermatol Ther 2019; 32: e12997.

https://doi.org/10.1111/dth.12997 DOI: https://doi.org/10.1111/dth.12997

Fawzy M, Nofal E, Abdelkhalek N, Ehab R. Intralesional bivalent and quadrivalent human papillomavirus vaccines didn't significantly enhance the response of multiple anogenital warts when co-administered with intralesional Candida antigen immunotherapy: a randomized controlled trial. Arch Dermatol Res 2023; 315: 2813-2823.

https://doi.org/10.1007/s00403-023-02698-z DOI: https://doi.org/10.1007/s00403-023-02698-z

Hodeib AAE, Al-Sharkawy BG, Hegab DS, Talaat RAZ. A comparative study of intralesional injection of Candida albicans antigen, bleomycin and 5-fluorouracil for treatment of plane warts. J Dermatolog Treat 2021; 32: 663-668.

https://doi.org/10.1080/09546634.2019.1688236 DOI: https://doi.org/10.1080/09546634.2019.1688236

Marei A, Alakad R, Wahid RM. Evaluation of intralesional Candida antigen in diabetic patients with multiple warts. J Cosmet Dermatol 2021; 20: 1248-1253.

https://doi.org/10.1111/jocd.13718 DOI: https://doi.org/10.1111/jocd.13718

Marei A, Nofal A, Alakad R, Abdel-Hady A. Combined bivalent human papillomavirus vaccine and Candida antigen versus Candida antigen alone in the treatment of recalcitrant warts. J Cosmet Dermatol 2020; 19: 758-762.

https://doi.org/10.1111/jocd.13077 DOI: https://doi.org/10.1111/jocd.13077

Nasr M, Abdelaty S, Elkholy BM. A comparative clinico-dermoscopic study of intralesional injection of combined digoxin and furosemide, Candida antigen, and vitamin D3 for multiple warts. J Cosmet Dermatol 2023; 22: 1344-1353.

https://doi.org/10.1111/jocd.15581 DOI: https://doi.org/10.1111/jocd.15581

Nassar A, Alakad R, Essam R, Bakr NM, Nofal A. Comparative efficacy of intralesional Candida antigen, intralesional bivalent human papilloma virus vaccine, and cryotherapy in the treatment of common warts. J AM Acad Dermatol 2022; 87: 419-421.

https://doi.org/10.1016/j.jaad.2021.08.040 DOI: https://doi.org/10.1016/j.jaad.2021.08.040

Nassar A, Mostafa M, Khashaba SA. Photodynamic therapy versus candida antigen immunotherapy in plane wart treatment: a comparative controlled study. Photodiagnosis Photodyn Ther 2020; 32: 101973.

https://doi.org/10.1016/j.pdpdt.2020.101973 DOI: https://doi.org/10.1016/j.pdpdt.2020.101973

Nassar A, Nofal A, Bakr NM, Essam R, Alakad R. Correlation of serum interleukin 17 and macrophage migration inhibitory factor levels with clinical response to intralesional Candida antigen and their potential use as predictors of clinical outcome in patients with multiple common warts. J Cosmet Dermatol 2022; 21: 3970-3978.

https://doi.org/10.1111/jocd.14688 DOI: https://doi.org/10.1111/jocd.14688

Nofal A, Adel L, Fawzy M, Elkholy BM. Intralesional immunotherapy for multiple recalcitrant plantar warts: Candida antigen is superior to intralesional purified protein derivative. Dermatol Ther 2022; 35: e15440.

https://doi.org/10.1111/dth.15440 DOI: https://doi.org/10.1111/dth.15440

Nofal A, Alakad R. Intralesional immunotherapy for the treatment of anogenital warts in pediatric population. J Dermatolog Treat 2022; 33: 1042-1046.

https://doi.org/10.1080/09546634.2020.1800573 DOI: https://doi.org/10.1080/09546634.2020.1800573

Nofal A, Alakad R, Fouda I, Fawzy MM. Intralesional antigen immunotherapy in the treatment of periungual warts. J Cutan Med Surg 2021; 25: 286-292.

https://doi.org/10.1177/1203475420988859 DOI: https://doi.org/10.1177/1203475420988859

Nofal A, Albalat W, Ismail A, Khattab FM. Immunotherapeutic modalities for the treatment of recalcitrant plantar warts: a comparative study. J Dermatolog Treatt 2022; 33: 922-927.

https://doi.org/10.1080/09546634.2020.1789540 DOI: https://doi.org/10.1080/09546634.2020.1789540

Nofal A, Soliman M, Hamdy F, Alakad R. Intralesional Candida antigen versus intralesional tuberculin in the treatment of recalcitrant genital warts: a comparative study. J Am Acad Dermatol 2020; 82: 1512-1514.

https://doi.org/10.1016/j.jaad.2019.12.050 DOI: https://doi.org/10.1016/j.jaad.2019.12.050

Nofal A, Yehia E, Khater E, Bessar H. Alternating intralesional purified protein derivative and Candida antigen versus either agent alone in the treatment of multiple common warts. J Am Acad Dermatol 2020; 83: 208-210.

https://doi.org/10.1016/j.jaad.2020.01.054 DOI: https://doi.org/10.1016/j.jaad.2020.01.054

Rageh RM, Hewedy ES, Hegab DS. Intralesional injection of Candida albicans antigen versus measles, mumps, and rubella vaccine for treatment of plantar warts. Acta Dermatovenerol Alp Pannonica Adriat 2021; 30: 1-5.

https://doi.org/10.15570/actaapa.2021.1 DOI: https://doi.org/10.15570/actaapa.2021.1

Tawfik NZ, Eyada MMK, Abdel El Hamid RE, Halim HM. Intralesional injection of purified protein derivative versus Candida antigen in treatment of genital warts. Dermatolog Ther 2022; 35: e15762.

https://doi.org/10.1111/dth.15762 DOI: https://doi.org/10.1111/dth.15762

Youssef EMK, Eissa MAA, Bakr RM. Intralesional Candida albicans antigen versus intralesional zinc sulfate in treatment of cutaneous warts. Arch Dermatol Res 2023; 315: 1305-1314.

https://doi.org/10.1007/s00403-022-02499-w DOI: https://doi.org/10.1007/s00403-022-02499-w

Nofal A, Salah E, Nofal E, Yosef A. Intralesional antigen immunotherapy for the treatment of warts: current concepts and future prospects. Am J Clin Dermatol 2013; 14: 253-260.

https://doi.org/10.1007/s40257-013-0018-8 DOI: https://doi.org/10.1007/s40257-013-0018-8

Sorour NE, Elesawy FM, Abdou AG, Abdelazeem SE, Akl EM. Intralesional injection of vitamin D in verruca vulgaris increases cathelicidin (LL37) expression: therapeutic and immunohistochemical study. J Dermatol Treat 2022; 33: 291-296.

https://doi.org/10.1080/09546634.2020.1750554 DOI: https://doi.org/10.1080/09546634.2020.1750554

Perman M, Sterling JB, Gaspari A. The painful purple digit: an alarming complication of Candida albicans antigen treatment of recalcitrant warts. Dermatitis 2005; 16: 38-40.

https://doi.org/10.1097/01206501-200503000-00008 DOI: https://doi.org/10.1097/01206501-200503000-00008

Published

2024-10-18

How to Cite

Chang, C.-H., Sung, Z.-Y., & Huang, Y.-C. (2024). Efficacy of Intralesional Candida Injection in the Treatment of Cutaneous Warts: A Systematic Review and Meta-Analysis. Acta Dermato-Venereologica, 104, adv40819. https://doi.org/10.2340/actadv.v104.40819