



LETTER TO THE EDITOR Year : 2019 | Volume : 13 | Issue : 2 | Page : 91-93 Bleomycin therapy using multipuncture technique for resistant warts



Asli Bilgic1, Ayse Akman-Karakas2

1 Dermatology Clinic, Antalya Training and Research Hospital, University of Health Sciences, Antalya, Turkey

2 Department of Dermatology and Venereology, School of Medicine, Akdeniz University, Antalya, Turkey

Date of Web Publication 25-Sep-2019 Correspondence Address:

Dr. Asli Bilgic

Dermatology Clinic, Antalya Training and Research Hospital, University of Health Sciences, Antalya

Turkey

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/TJD.TJD_11_19



How to cite this article:

Bilgic A, Akman-Karakas A. Bleomycin therapy using multipuncture technique for resistant warts. Turk J Dermatol 2019;13:91-3

How to cite this URL:

Bilgic A, Akman-Karakas A. Bleomycin therapy using multipuncture technique for resistant warts. Turk J Dermatol [serial online] 2019 [cited 2020 Sep 26];13:91-3. Available from: http://www.tjdonline.org/text.asp?2019/13/2/91/267828





Sir,



The case report titled “Successful Treatment of a Resistant Periungual Wart Case with Bleopuncture Method” by Yalçın et al. in the Turkish Journal of Dermatology (Turk J Dermatol 2018; 12: 191–3) recalled an often-ignored bleomycin therapy in the treatment of resistant warts.[1]



Cutaneous warts sometimes fail to respond to routine treatments (cryotherapy, electrosurgery, topical salicylic acid, fluorouracil, potassium hydroxide, and retinoid treatments and combinations). In these cases, bleomycin therapy has been a treatment option which has been in the literature for a long time, but is not preferred too frequently.



Bleomycin is considered as a third-line therapy for resistant warts and has been regarded as level 1 strength of evidence for the treatment of warts.[2] It is obtained from “Streptomyces verticillus” and shows an inhibitory effect on the virus and the host cell by inhibiting DNA and protein synthesis. In the treatment of warts, two application methods were noteworthy until recent years. First, intralesional bleomycin (IL Bleo) therapy has been shown to be a very effective treatment method (success rates vary between 14% and 99%), but it is not often preferred because of its rare however scary side effects (pain, chemical cellulitis, postinflammatory hyperpigmentation, Raynaud's phenomenon, tissue necrosis, onychodystrophy, and flagellate hyperpigmentation).[3]



These side effects can be largely preserved by the application of bleomycin utilizing “multipuncture” technique. In our case report and literature review published in 2016, we reviewed the efficacy of bleomycin using “multipuncture” technique in the treatment of warts.[4] According to our literature review, 74%–100% cure rates were obtained for palmoplantar and periungual warts which are resistant to other topical therapies. It was applied in the range of 0.1–3 U/ml in 2–4-week intervals. No significant adverse effects were observed during and after the procedure except for the local pain.[4],[5],[6],[7],[8],[9] In our case report, a 56-year-old female with a 3-year history of plantar warts (previously treated with salicylic acid, fluorouracil, and cryotherapy without any success) was treated with multipuncture bleomycin therapy.[4] A concentration of 3 U/mL bleomycin was applied with occlusion after prickling the warts, and it was kept on the warts with a stretch film for 12 h. The procedure was repeated 4 times with 2-week intervals. At the end of 2 months, complete resolution was achieved.[4]



Bleomycin can be found in 15 and 30 mg vials in our country and its cost varies between 30 and 80 TL. The most preferred procedure for multipuncture technique was to prick the wart through the intradermal area with a sterile needle followed by preparing a 1 U/mL bleomycin in saline solution (a vial containing 15 units of bleomycin and 15 mL of normal saline solution is mixed to achieve a concentration of 1 U/mL). One unit is equivalent to the activity of 1 mg of bleomycin. After that, this bleomycin solution dropped to the area or on the gauze and then closed on the area for a few hours with sterile gauze.[1],[4],[5],[6],[7],[8],[9] A small number of recurrences were observed in 6–18-month follow-up periods in the treated warts [6],[8],[9] [Table 1]. Table 1: Multipuncture bleomycin therapy for warts are summarized



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Furthermore, in recent years, there have been small studies evaluating the efficacy and safety of topical bleomycin therapy applied by coated microneedles or combined with microneedling, electroporation, or ablative laser therapy.[10],[11],[12],[13],[14],[15] In some of them, researchers even compared it to IL Bleo, intralesional saline, or cryotherapy.[13],[14],[15] First, Konicke and Olasz presented three patients with warts who were cured with microneedling combined with topical application of 1 U/mL bleomycin (MN + Bleo). All patients were cured after an average of four treatments performed in every 2–4 weeks, and no recurrence was seen in 3–5 months' time.[10]



Moreover, in an innovative work, Lee et al. created bleomycin-coated microneedles and studied the mechanical properties and drug delivery properties of them. They demonstrated that microneedles delivered bleomycin successfully into the subepidermal skin layer of warts and more than 80% of the bleomycin dissolved into the skin in vitro within 15 min. To conclude, they suggested that bleomycin-tip-coated microneedles are an effective, easy, and painless way for wart treatment.[11] Suh et al. used a different method and they treated warts with bleomycin application (1 U/mL) after ablative carbon dioxide fractional laser (three passes of laser with single-pulse treatment parameters of 180 mJ pulse energy and 100 spots/cm 2 density in the static mode). Seventeen patients with a total of 38 warts were successfully treated at every 2 weeks with six consecutive sessions of this protocol.[12] Ryu et al. conducted a comparative study to evaluate the therapeutic effects of newly developed bleomycin microneedle patch regards to cryotherapy. They recruited 42 patients with more than two wart lesions in each and the lesions were treated by one of the above-mentioned methods randomly. Their study demonstrated 76.2% clearance rate for cryotherapy and 61.9% clearance rate for the bleomycin microneedle patch at week 16. This new therapeutic method was found to be an effective, convenient, and painless treatment modality when compared with cryotherapy.[13] In another study, Al-Naggar et al. compared IL Bleo (with a single injection of 1 U/mL bleomycin) and microneedling with topical spraying of bleomycin (MN + Bleo) performed every 2 weeks for a maximum of four sessions. Sixty patients were recruited to the study and divided into two groups equally. They presented 83.3% complete clearance rate of warts in the MN + Bleo group compared to 70% in the IL Bleo group.[14] Gamil et al. recently published another comparative study where 54 patients were divided into three groups (18 patients each). The first group was treated by dermapen with topical bleomycin (1 mg/1 mL) for a maximum of four sessions at 2-week intervals. On the other hand, the second group received IL Bleo (1 unit/mL) for a maximum of four sessions at 3-week intervals, and the control group was intralesional saline for a maximum of four sessions. Complete clearance was found to be highest in Group 1 (88.9%) as opposed to 83.3% in Group 2 and 5.6% in the control group.[15]



In the recent case of Yalçın et al., a single-session multipuncture method was used to successfully treat periungual warts.[1] As is seen in these case reports and the literature, multipuncture technique is a safe, effective, and well-tolerated treatment. Thus, it should be included in our preferences as its use is easy to apply, it has good results and comfortable for patients, and it keeps the cost low for both the patient and the health system. In the following years, multipuncture bleomycin therapy can take part in the higher step in the treatment algorithm of recalcitrant warts.



However, there is a need for prospective controlled studies to determine the most appropriate frequency and dosage of the method, standardization of the application, and the side effect profile.



Financial support and sponsorship



Nil.



Conflicts of interest



There are no conflicts of interest.







References

1.

Yalçın B, Yıldırım B, Artüz F. Successful Treatment of a Resistant Periungual Wart Case with Bleopuncture Method. Turk J Dermatol 2018; 12:191-3. 2.

Bacelieri R, Johnson SM. Cutaneous warts: An evidence-based approach to therapy. Am Fam Physician 2005;72:647-52. 3.

Lewis TG, Nydorf ED. Intralesional bleomycin for warts: A review. J Drugs Dermatol 2006;5:499-504. 4.

Temel AB, Akman-Karakas A. Successful treatment of plantar warts with bleomycin using multi-puncture technique and review of multi-puncture applications. J Res Dev 2016;4:137. 5.

Shelley WB, Shelley ED. Intralesional bleomycin sulfate therapy for warts. A novel bifurcated needle puncture technique. Arch Dermatol 1991;127:234-6. 6.

Munn SE, Higgins E, Marshall M, Clement M. A new method of intralesional bleomycin therapy in the treatment of recalcitrant warts. Br J Dermatol 1996;135:969-71. 7.

Sardana K, Garg V, Relhan V. Complete resolution of recalcitrant periungual/subungual wart with recovery of normal nail following “prick” method of administration of bleomycin 1%. Dermatol Ther 2010;23:407-10. 8.

AlGhamdi KM, Khurram H. Successful treatment of periungual warts with diluted bleomycin using translesional multipuncture technique: A pilot prospective study. Dermatol Surg 2011;37:486-92. 9.

Alghamdi KM, Khurram H. Successful treatment of plantar warts with very diluted bleomycin using a translesional multipuncture technique: Pilot prospective study. J Cutan Med Surg 2012;16:250-6. 10.

Konicke K, Olasz E. Successful treatment of recalcitrant plantar warts with bleomycin and microneedling. Dermatol Surg 2016;42:1007-8. 11.

Lee HS, Ryu HR, Roh JY, Park JH. Bleomycin-coated microneedles for treatment of warts. Pharm Res 2017;34:101-12. 12.

Suh JH, Lee SK, Kim MS, Lee UH. Efficacy of bleomycin application on periungual warts after treatment with ablative carbon dioxide fractional laser: A pilot study. J Dermatolog Treat 2019;6:1-5. 13. et al. Efficacy of a bleomycin microneedle patch for the treatment of warts. Drug Deliv Transl Res 2018;8:273-80.

Ryu HR, Jeong HR, Seon-Woo HS, Kim JS, Lee SK, Kim HJ,Efficacy of a bleomycin microneedle patch for the treatment of warts. Drug Deliv Transl Res 2018;8:273-80. 14.

Al-Naggar MR, Al-Adl AS, Rabie AR, Abdelkhalk MR, Elsaie ML. Intralesional bleomycin injection vs. microneedling-assisted topical bleomycin spraying in treatment of plantar warts. J Cosmet Dermatol 2019;18:124-8. 15.

Gamil HD, Nasr MM, Khattab FM, Ibrahim AM. Combined therapy of plantar warts with topical bleomycin and microneedling: A comparative controlled study. J Dermatolog Treat 2019;17:1-6.







Tables

[Table 1]



