Venous Leg Ulcers: Advanced Therapies and New Technologies

Hubert Aleksandrowicz, Agnieszka Owczarczyk-Saczonek, Waldemar Placek, Hubert Aleksandrowicz, Agnieszka Owczarczyk-Saczonek, Waldemar Placek

Abstract

The prevalence of venous leg ulcers (VLUs) differs between 1.5% and 3% in the general population. The challenge in treating VLUs is common recurrence. Moreover, VLUs can be resistant to healing, despite appropriate treatment. In these cases, advanced wound therapies should be considered. The number of new technologies, applied in VLUs treatment, has increased in the last years. These therapies include biophysical interventions such as ultrasound therapy, electrical stimulations, electromagnetic therapy, or phototherapy. Furthermore, stem cell therapies, biologic skin equivalents, platelet-rich plasma therapy, oxygen therapies, anti-TNF therapy, or negative pressure wound therapy are advanced venous ulcer therapeutic methods that may support the standard of care. Medical devices, such as a muscle pump activator, or intermittent pneumatic compression device, may be especially useful for specific subgroups of patients suffering from VLUs. Some of the above-mentioned technologies require broader evidence of clinical efficacy and are still considered experimental therapies in dermatology.

Keywords: advanced therapies; experimental dermatology; new technologies; venous leg ulcers; wound treatment.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Neumann H.A.M., Cornu-Thenard A., Junger M., Mosti G., Munte K., Partsch H., Rabe E., Ramelet A.-A., Streit M. Evidence-based (S3) guidelines for diagnostics and treatment of venous leg ulcers. J. Eur. Acad. Dermatol. Venereol. 2016;30:1843–1875. doi: 10.1111/jdv.13848.
    1. Harris C., Duong R., Vanderheyden G., Byrnes B., Cattryse R., Orr A., Keast D. Evaluation of a muscle pump-activating device for non-healing venous leg ulcers. Int. Wound J. 2017;14:1189–1198. doi: 10.1111/iwj.12784.
    1. Sugerman H.J., Sugerman E.L., Wolfe L., Kellum J.M., Jr., Schweitzer M.A., DeMaria E.J. Risks and Benefits of Gastric Bypass in Morbidly Obese Patients with Severe Venous Stasis Disease. Ann. Surg. 2001;234:41–46. doi: 10.1097/00000658-200107000-00007.
    1. Wilson J.A., Clark J.J. Obesity: Impediment to postsurgical wound healing. Adv. Skin Wound Care. 2004;17:426–435. doi: 10.1097/00129334-200410000-00013.
    1. Alvarez O.M., Markowitz L., Parker R., Wendelken M.E. Faster Healing and a Lower Rate of Recurrence of Venous Ulcers Treated with Intermittent Pneumatic Compression: Results of a Randomized Controlled Trial. Eplasty. 2020;20:e6.
    1. Chooi Y.C., Ding C., Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10. doi: 10.1016/j.metabol.2018.09.005.
    1. Apovian C.M. Obesity: Definition, comorbidities, causes, and burden. Am. J. Manag. Care. 2016;22((Suppl. 7)):s176–s185.
    1. Cereceres S., Lan Z., Bryan L., Whitely M., Wilems T., Greer H., Alexander E.R., Taylor R.J., Bernstein L., Cohen N., et al. Bactericidal activity of 3D-printed hydrogel dressing loaded with gallium maltolate. APL Bioeng. 2019;3:026102. doi: 10.1063/1.5088801.
    1. Aziz Z., Cullum N. Electromagnetic therapy for treating venous leg ulcers. Cochrane Databas Syst. Rev. 2015;2015:CD002933. doi: 10.1002/14651858.CD002933.pub6.
    1. Sawad A.B., Turkistani F. Treatment of venous leg ulcers using bilayered living cellular construct. J. Comp. Eff. Res. 2020;9:907–918. doi: 10.2217/cer-2020-0076.
    1. Cuomo R., Nisi G., Grimaldi L., Brandi C., D’Aniello C. Use of ultraportable vacuum therapy systems in the treatment of venous leg ulcer. Acta Biomed. 2017;88:297–301. doi: 10.23750/abm.v88i3.5737.
    1. Kranke P., Bennett M.H., Martyn-St James M., Schnabel A., Debus S.E., Weibel S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst. Rev. 2015;6:CD004123. doi: 10.1002/14651858.CD004123.pub4.
    1. Bavaresco T., Pires A.U.B., Moraes V.M., Osmarin V.M., Silveira D.T., Lucena A.F. Low-level laser therapy for treatment of venous ulcers evaluated with the Nursing Outcome Classification: Study protocol for a randomized controlled trial. Trials. 2018;19:372. doi: 10.1186/s13063-018-2729-x.
    1. Harries R.L., Bosanquet D.C., Harding K.G. Wound bed preparation: TIME for an update. Int. Wound J. 2016;13((Suppl. 3)):8–14. doi: 10.1111/iwj.12662.
    1. Coalson E., Bishop E., Liu W., Feng Y., Spezia M., Liu B., Shen Y., Wu D., Du S., Li A.J., et al. Stem cell therapy for chronic skin wounds in the era of personalized medicine: From bench to bedside. Genes Dis. 2019;6:342–358. doi: 10.1016/j.gendis.2019.09.008.
    1. Evans R., Kuhnke J.L., Burrows C., Kayssi A., Labreque C., O’Sullivan-Drombolis D., Houghton P. Foundations of Best Practice for Skin and Wound Management. A Supplement of Wound Care Canada. 2019. [(accessed on 10 September 2021)]. Best Practice Recommendations for the Prevention and Management of Venous Leg Ulcers.70p. Available online: .
    1. Fan W., Yang B., Hu X., Yang X., Shi C., Liu G. Safety and efficacy of larval therapy on treating leg ulcers: A protocol for systematic review and meta-analysis. BMJ Open. 2020;10:e039898. doi: 10.1136/bmjopen-2020-039898.
    1. Bazaliński D., Kózka M., Karnas M., Więch P. Effectiveness of Chronic Wound Debridement with the Use of Larvae of Lucilia sericata. J. Clin. Med. 2019;8:1845. doi: 10.3390/jcm8111845.
    1. Romanelli M., Piaggesi A., Scapagnini G., Dini V., Janowska A., Iacopi E., Scarpa C., Fauverghe S., Bassetto F. EUREKA study-the evaluation of real-life use of a biophotonic system in chronic wound management: An interim analysis. Drug Des. Devel. Ther. 2017;11:3551–3558. doi: 10.2147/DDDT.S142580.
    1. Beheshti A., Shafigh Y., Parsa H., Zangivand A.A. Comparison of high-frequency and MIST ultrasound therapy for the healing of venous leg ulcers. Adv. Clin. Exp. Med. 2014;23:969–975. doi: 10.17219/acem/37353.
    1. Raffetto J.D., Ligi D., Maniscalco R., Khalil R.A., Mannello F. Why venous leg ulcers have difficulty healing: Overview on pathophysiology, clinical consequences, and treatment. J. Clin. Med. 2021;10:29. doi: 10.3390/jcm10010029.
    1. Rajendran S.B., Challen K., Wright K.L., Hardy J.G. Electrical Stimulation to Enhance Wound Healing. J. Funct. Biomater. 2021;12:40. doi: 10.3390/jfb12020040.
    1. Elio C., Fontani V., Rinaldi S., Gasbarro V. REAC-induced endogenous bioelectric currents in the treatment of venous ulcers: A three-arm randomized controlled prospective study. Acta Dermatovenerol. Alp. Pannonica Adriat. 2020;29:109–113.
    1. Cullum N., Liu Z. Therapeutic ultrasound for venous leg ulcers. Cochrane Database Syst. Rev. 2017;5:CD001180. doi: 10.1002/14651858.CD001180.pub4.
    1. Illescas-Montes R., Atkinson R.A., Cullum N. Low-level light therapy for treating venous leg ulcers. Cochrane Database Syst. Rev. 2018;2018:CD013061. doi: 10.1002/14651858.CD013061.
    1. Mutluoglu M., Cakkalkurt A., Uzun G., Aktas S. Topical Oxygen for Chronic Wounds: A PRO/CON Debate. J. Am. Coll. Clin. Wound Spec. 2014;5:61–65. doi: 10.1016/j.jccw.2014.12.003.
    1. Andrade S.M., Vieira Santos I.C.R. Hyperbaric oxygen therapy for wound care. Rev. Gaúcha Enferm. 2016;37:e59257. doi: 10.1590/1983-1447.2016.02.59257.
    1. Ren S.Y., Liu Y.S., Zhu G.J., Liu M., Shi S.H., Ren X.D., Hao Y.G., Gao R.D. Strategies and challenges in the treatment of chronic venous leg ulcers. World J. Clin. Cases. 2020;8:5070–5085. doi: 10.12998/wjcc.v8.i21.5070.
    1. Thistlethwaite K.R., Finlayson K.J., Cooper P.D., Brown B., Bennett M.H., Kay G., O’Reilly M.T., Edwards H.E. The effectiveness of hyperbaric oxygen therapy for healing chronic venous leg ulcers: A randomized, double-blind, placebo-controlled trial. Wound Repair Regen. 2018;26:324–331. doi: 10.1111/wrr.12657.
    1. Sultan S., Tawfick W., Kavanagh E.P., Hynes N. Topical Wound Oxygen Versus Conventional Compression Dressings in the Management of Refractory Venous. [(accessed on 10 September 2021)]. Available online: .
    1. Alkhateep Y., Zaid N., Fareed A. Negative pressure wound therapy for chronic venous ulcer: A randomized-controlled study. Egypt. J. Surg. 2018;37:196. doi: 10.4103/ejs.ejs_147_17.
    1. Dumville J.C., Land L., Evans D., Peinemann F. Negative pressure wound therapy for treating leg ulcers. Cochrane Database Syst. Rev. 2015;2015:CD011354. doi: 10.1002/14651858.CD011354.pub2.
    1. Kucharzewski M., Mieszczański P., Wilemska-Kucharzewska K., Taradaj J., Kuropatnicki A., Sliwiński Z. The application of negative pressure wound therapy in the treatment of chronic venous leg ulceration: Authors experience. Biomed. Res. Int. 2014;2014:297230. doi: 10.1155/2014/297230.
    1. Megahed M.A., Rageh T.M., Nassar A.T., Abdel Razek M.E. The role of autologous platelet-rich plasma in healing of gaping and chronic wounds. Menoufia. Med. J. 2019;32:723–728.
    1. Suthar M., Gupta S., Bukhari S., Ponemone V. Treatment of chronic non-healing ulcers using autologous platelet rich plasma: A case series. J. Biomed. Sci. 2017;24:16. doi: 10.1186/s12929-017-0324-1.
    1. Huber S.C., de Moraes Martinelli B., Quintero M., de Paula L.Í.S., Cataldo J.L., de Lima Montalvão S.A., Annichino-Bizzacchi J.M. A case series of platelet rich plasma in chronic venous ulcers. Regen. Ther. 2021;18:51–58. doi: 10.1016/j.reth.2021.03.005.
    1. Martinez-Zapata M.J., Martí-Carvajal A.J., Solà I., Expósito J.A., Bolíbar I., Rodríguez L., Garcia J., Zaror C. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst. Rev. 2016;5:CD006899. doi: 10.1002/14651858.CD006899.pub3.
    1. Fox J.D., Baquerizo-Nole K.L., Keegan B.R., Macquhae F., Escandon J., Espinosa A., Perez C., Romanelli P., Kirsner R.S. Adalimumab treatment leads to reduction of tissue tumor necrosis factor-alpha correlated with venous leg ulcer improvement: A pilot study. Int. Wound J. 2016;13:963–966. doi: 10.1111/iwj.12497.
    1. Wallace H.J., Stacey M.C. Levels of tumor necrosis factor-α (TNF-α) and soluble TNF receptors in chronic venous leg ulcers—Correlations to healing status. J. Investig. Dermatol. 1998;110:292–296. doi: 10.1046/j.1523-1747.1998.00113.x.
    1. Charles C.A., Romanelli P., Martinez Z.B., Ma F., Roberts B., Kirsner R.S. Tumor necrosis factor-alfa in nonhealing venous leg ulcers. J. Am. Acad. Dermatol. 2009;60:951–955. doi: 10.1016/j.jaad.2008.09.012.
    1. Cowin A.J., Hatzirodos N., Rigden J., Fitridge R., Belford D.A. Etanercept decreases tumor necrosis factor-alpha activity in chronic wound fluid. Wound Repair Regen. 2006;14:421–426. doi: 10.1111/j.1743-6109.2006.00141.x.
    1. Hadian Y., Bagood M.D., Dahle S.E., Sood A., Isseroff R.R. Interleukin-17: Potential Target for Chronic Wounds. Mediat. Inflamm. 2019;2019:1297675. doi: 10.1155/2019/1297675.
    1. Matias M.A., Saunus J.M., Ivanovski S., Walsh L.J., Farah C.S. Accelerated wound healing phenotype in Interleukin 12/23 deficient mice. J. Inflamm. 2011;8:39. doi: 10.1186/1476-9255-8-39.
    1. Verkey M., Ding J., Tredget E. The potential role of stem cells in wound healing. Wounds UK. 2013;9:60–66.
    1. Raghuram A.C., Yu R.P., Lo A.Y., Sung C.J., Bircan M., Thompson H.J., Wong A.K. Role of stem cell therapies in treating chronic wounds: A systematic review. World J. Stem Cells. 2020;12:659–675. doi: 10.4252/wjsc.v12.i7.659.
    1. Dehkordi A.N., Babaheydari F.M., Chehelgerdi M., Dehkordi S.R. Skin tissue engineering: Wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res. Ther. 2019;10:111. doi: 10.1186/s13287-019-1212-2.
    1. Holm J.S., Toyserkani N.M., Sorensen J.A. Adipose-derived stem cells for treatment of chronic ulcers: Current status. Stem Cell Res. Ther. 2018;9:142. doi: 10.1186/s13287-018-0887-0.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する