Scientific letter
Microneedling with bleomycin as a treatment for periungueal and subungueal warts
Micropunciones de bleomicina como tratamiento para verrugas periungueales y subungueales
Ana Morelló-Vicente, Javier Antoñanzas, Agustín España
Corresponding author
Department of Dermatology, University Clinic of Navarra, School of Medicine, University of Navarra, Spain
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Patient 2: (c) periungueal wart before treatment and (d) after treatment.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Periungual and subungual warts (P-SW) are fibroepithelial tumors of the nail unit caused by the human papillomavirus. The diagnosis is mainly clinical. Differential diagnosis with squamous cell carcinoma or Bowen's disease must be made in refractory lesions.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> Treatment of P-SW is a challenge because of their recurrence, treatment tolerability and efficacy<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3,4</span></a> and the further complication that it can lead to nail plate damage.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Bleomycin is a cytotoxic agent that inhibits DNA and protein synthesis. Satisfactory results have been reported with intralesional bleomycin treatment with concentrations ranging from 1 to 3<span class="elsevierStyleHsp" style=""></span>U/mL.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Some studies have used bleomycin with a multi-puncture technique, which also provides good response.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">This is a retrospective and descriptive study including five patients, 3 female and 2 male, ages 16–60 years presenting P-SW who did not respond to other treatments. The time of course of the lesions was between 8 months and 8 years. The diagnosis was made based on history and clinical features (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1A, 1C</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The same method was used in all patients following the technique used for other skins lesions in our center. First, the nail plate was cut until the wart was totally exposed and 2% intralesional Mepivacaine was injected to anesthetize the area. Then, bleomycin was dropped onto the lesion at a concentration of 1.5<span class="elsevierStyleHsp" style=""></span>IU/ml and multiple punctures on the wart surface with a 25-gauge 5/8 0.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>16 needle were made. Then occlusion was applied for 12<span class="elsevierStyleHsp" style=""></span>h. The patients were followed-up one and three months after the treatment. Cure was defined as the total absence of the lesion.</p><p id="par0025" class="elsevierStylePara elsevierViewall">All patients achieved total remission, but the number of sessions required by each individual was different. Two patients needed one session, other two needed two sessions and only one needed three sessions. If more than one session was needed, the period of time between them was 2–4 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1B, 1D</a>).</p><p id="par0030" class="elsevierStylePara elsevierViewall">After the treatment, moderate pain was the major complain of the patients. There were no other local or systemic side effects reported except a slight alteration of sensation in one patient.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The number of reports using microneeding technique exclusively in P-SW is scarce. Varying concentrations of bleomycin solution have been used in different studies due to the lack of standardization.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Local skin reactions after bleomycin injections include transient symptoms of erythema, edema, blackening, eschar formation, pain, and pigmentary changes. Less common adverse reactions include gangrene, onychodystrophy, Raynaud's phenomenon, scleroderma, and flagellate erythema.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2,5</span></a> Contraindications for bleomycin include pregnancy, Raynaud phenomenon, peripheral vascular disease, and bleomycin intolerance.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Microneedling is a minimally invasive procedure. The microneedles penetrate the epidermis without removing it, creating micropores through the stratum corneum and into the underlying epidermis, leading to the rapid delivery of topical medications into the dermal microcirculation.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Gamil et al. compared the clinical response between microneedling with bleomycin, intralesional bleomycin and placebo in plantar warts. The best results were obtained using the microneedling technique with a complete clearance in 88.9% of the patients versus 83.3% with the intralesional treatment.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> These results are consistent with those reported by Al-Naggar et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Di Chiacchio et al. compared treatment with intralesional bleomycin alone and followed by electroporation in ungual warts. The latter technique provided better response with a clearance of 87.7 versus 50%.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In our study, all the patients have complete response using the microneedling technique without any important side effects, with only one of the patients needing three sessions.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Treatment with bleomycin using the microneedling technique offers promising results with few side effects in P-SW. During the follow-up no recurrence was recorded. Further studies are required to determine the cure rate, optimum follow-up and the therapeutic dose.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0070" class="elsevierStylePara elsevierViewall">Written informed consent was obtained.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no source of funding.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1658 "Ancho" => 1505 "Tamanyo" => 158196 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient 1: (a) subungueal wart before treatment and (b) after treatment. Patient 2: (c) periungueal wart before treatment and (d) after treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ungual warts: comparison of treatment with intralesional bleomycin and electroporation in terms of efficacy and safety" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N.G. Di Chiacchio" 1 => "N. Di Chiacchio" 2 => "P.R. Criado" 3 => "C.H.M. Brunner" 4 => "M.V.R. Suaréz" 5 => "W. Belda Junior" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdv.15815" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2019" "volumen" => "33" "paginaInicial" => "2349" "paginaFinal" => "2354" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31314920" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of intralesional bleomycin in the management of ungual warts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Singal" 1 => "G. Chander" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ski Appendage Disord" "fecha" => "2020" "volumen" => "6" "paginaInicial" => "346" "paginaFinal" => "350" "itemHostRev" => array:3 [ "pii" => "S0016508508009037" "estado" => "S300" "issn" => "00165085" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined therapy of plantar warts with topical bleomycin and microneedling: a comparative controlled study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H.D. Gamil" 1 => "M.M. Nasr" 2 => "F.M. Khattab" 3 => "A.M. Ibrahim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/09546634.2019.1612837" "Revista" => array:5 [ "tituloSerie" => "J Dermatol Treat" "fecha" => "2020" "volumen" => "31" "paginaInicial" => "235" "paginaFinal" => "240" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intralesional bleomycin injection vs microneedling-assisted topical bleomycin spraying in treatment of plantar warts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.R. Al-Naggar" 1 => "A.S. Al-Adl" 2 => "A.R. Rabie" 3 => "M.R. Abdelkhalk" 4 => "M.L. Elsaie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jocd.12537" "Revista" => array:7 [ "tituloSerie" => "J Cosmet Dermatol" "fecha" => "2019" "volumen" => "18" "paginaInicial" => "124" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29687566" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022347614010154" "estado" => "S300" "issn" => "00223476" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and tolerability of intralesional bleomycin in dermatology: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Bik" 1 => "T. Sangers" 2 => "K. Greveling" 3 => "E. Prens" 4 => "M.H. Dmsc" 5 => "M. 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