PULSED DYE LASER TREATMENT FOR RECALCITRANT VIRAL WARTS: AUTO-SIMULTANEOUS LASER TREATMENT

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PULSED DYE LASER TREATMENT FOR RECALCITRANT VIRAL WARTS: AUTO-SIMULTANEOUS LASER TREATMENT *Yuki Tniguchi 1, Toshio Ohshiro 2, Tkfumi Ohshiro 1, Ktsumi Sski 1 1: Ohshiro Clinic, Shinnomchi, Tokyo, Jpn 2: Jpn Medicl Lser Lortory, Shinnomchi, Tokyo, Jpn Verruc vulgris is enign prolifertive lesion of the skin cused y the humn ppillomvirus (HPV). It is commonly seen in dermtologic nd/or plstic surgery clinics. The dignosis is strightforwrd, ut the tretment of the lesion my e difficult nd lengthy. Severl tretment methods hve een reported ut no specific therpy of choice hs een developed. It hs een suggested tht pulsed dye lser tretment is highly effective in the tretment of virl wrts which hve not responded to other tretments. Pulsed dye lser tretment is sfe method with low side effects nd is mostly well-tolerted y ptients. Severl uthors hve recently reported the efficiency of pulsed dye lser tretment for wrts, ut no report hs pid ttention to the influence of low levels of lser irrdition out the periphery of the treted lesion which my induce immune ctivtion nd pin llevition. We elieve these effects re minly due to the therml nd trumtic simultneous Low rective Level Lser Therpy effect on photoiomodulted cells t the periphery of the treted lesion. We cll this coincident dulity of therml dmge nd therml stimultion uto-simultneous lser tretment. We report herein on pulse dye lser tretment for reclcitrnt huge virl wrt nd consider the vitl response. Key Words: verruc vulgris, humn ppillomvirus pulsed dye lser, high rective level lser tretment, low rective level lser therpy Introduction Addressee for Correspondence: Yuki Tniguchi MD, Ohshiro Clinic JR Shinnomchi Sttion Building 2F, 34 Shinnomchi, Shinjyuku-ku Tokyo, JAPAN 160-0016 Tel: +81-3-3352-0046 Fx: +81-3-3354-1103 E-mil: info@jmll.co.jp 2009 JMLL, Tokyo, Jpn Verruc vulgris, the common wrt, is enign epithelil prolifertion induced y types of the humn ppillomvirus (HPV). Verruce most commonly present singly or in groups on the dorsl spects of the fingers nd hnds s pinless, circumscried, firm elevted ppules with ppillomtous hyperkertotic surfce. The plms nd soles re less common sites nd present t these sites s mosic wrts. Wrts represent common prolem ffecting pproximtely 10% of the popultion 1). Although the mjority of cses re proly treted in generl prctice 2), recent survey found tht wrts represented 21% of referrls to dermtology deprtment, nd the tretment nd follow-up of these ptients constituted 19% of the worklod 3). Wrts often cuse pin nd my interfere with function. These complictions, cosmetic emrrssment, nd the risk of spreding to other res of skin re indictions for tretment. Severl tretment methods such s destructive gents (kertolytics, cryotherpy, curettge nd electrocutery, CO2 lser, photodynmic therpy), immunosuppressive gents (podophyllin, leomycin, retinoids), immune-modulting gents (interferon, imiquimod), or topicl virucidl gents (formldehyde, glutrl) hve een reported ut specific therpy of choice hs not yet een developed (Tle 1). As result, the tretment of wrts my ecome oth time-consuming nd expensive. Wrts tht fil to respond to conventionl tretment re considered to e reclcitrnt. The lesions re often frustrting for the ptient nd pose therpeutic prolem for Mnuscript received: Jnury 29th, 2009 Accepted for puliction: My 11th, 2009 Lser Therpy 19.1: 31-36 31

Tle 1. Conventionl methods Destructive gents Immunosuppressive gents Immuno-modulting gents Topicl virucidl gents Kertolytics cryotherpy Curettge Electrocutery CO2 lser Photodynmic therpy Podophyllin Bleomycin retinoids interferon imiquimod formldehyde glutrlldehyde Fig. 1: The ppernce of the lesion fter pring with sclpel Fig. 2: The 595 nm pulseddye lser (V em, Cndel Corp) Fig. 3: Cse 1 ) The clinicl ppernce efore tretment ) The ppernce fter 8 sessions Fig. 4: Cse 2 ) The clinicl ppernce efore tretment ) The ppernce fter 2 sessions 32 Tniguchi, Y ET AL

Fig. 5: Cse 3 ) The clinicl ppernce efore tretment ) The ppernce fter 3 sessions Fig. 6: Cse 4 ) The clinicl ppernce efore tretment ) The ppernce fter 2 sessions LT FOR RECALCITRANT VIRAL WARTS 33

the clinicin. Severl uthors hve recently reported tht tretment with the flshlmp-pumped dye lser (PDL) is new, sfe nd efficient tretment for simple nd reclcitrnt wrts. 4)- 12) The merit of PDL tretment is the lck of dverse side effects, with the pin fter pulsed dye lser irrdition eing especilly less thn other methods 9), so PDL tretment is cceptle for young dults who re unle to tke time off from their work. We elieve these eneficil effects re minly due to the therml nd trumtic simultneous Low rective Level Lser Therpy (LLLT) effect on photo-io-modulted cells t the periphery of the treted lesion. We would like to introduce successful PDL tretments for reclcitrnt virl wrts which hve een very difficult to cure with conventionl methods. Mteril nd Methods The wrts we treted were found on the soles, on the plms, on the fingertips, nd in the suungul regions. All wrts were defined s reclcitrnt wrs. The ge of the ptients rnged from 10 to 39 yers. All ptients hd received cryotherpy mny times every 1~2 weeks efore PDL tretment. Before tretment, the wrt ws pred with sclpel to remove hyperkertotic skin or deris just to the point of leeding, ecuse pring llows deeper penetrtion of the lser em into the wrt (Fig. 1). Tretment took plce without ny form of nesthesi including cryogen spry cooling. We used 595 nm long pulsed dye lser (V em, Cndel Corp; 4 to 20 J/f, 0.45 to 40 msec) (Fig. 2). The fluence ws 8 J/f with spot size of 7mm, nd the pulse durtion ws fixed t 0.45 msec. The dynmic cooling device, s incorported in the lser system, ws not ctivted. Three to five stcked pulses were indicted t frequency of 1 Hz to chieve the end point of tissue grying. The lesion ws treted every 4 weeks, until complete remission hd een chieved. When the lesion ws irrdited with the lser, ptients felt pinprick-like pin ccompnied y urning senstion over the treted re for few minutes. After lser exposure, ptients experienced significnt pin lsting for 0 to 2 dys. Other dverse side effects such s hemorrhge, listering or infection were never seen, nor were hypertrophic scr formtion, trophic scr formtion or secondry hyperpigmenttion chnges. Cse 1 A 20-yer-old mle noticed pinless, circumscried, firm elevted ppule with ppillomtous hyperkertotic surfce on the right sole when he ws 10 yers old. The lesion ws dignosed s verruce vulgris, nd he received multiple cryotherpy sessions every 2 weeks. Unfortuntely the lesion did not respond. On the contrry other virl wrts erupted nd grdully ecme dhesive. He stopped receiving cryotherpy fter he entered junior high school. When he visited our clinic, the lesion hd ecome very lrge, nd cused pin. He wnted the lesion treted to remove the pin, cosmetic emrrssment nd the risk of its spreding to other res of his skin. After 8 sessions the reclcitrnt huge virl wrt ws disppered (Fig. 3). Recurrence of the virl wrts did not occur in 1- yer postopertive follow-up. Cse 2 A 39-yer-old femle noticed virl wrts in the left hllux nd left pollex when she ws 37 yers old. She received cryotherpy every 2 weeks for 2 yers, ut the lesions filed to respond. After 2 PDL sessions t our clinic, the lesions disppered (Fig. 4), nd hve not reppered in postopertive 10-month follow-up period. Cse 3 A 24-yer-old femle noticed virl wrt on the right little finger when she ws 23 yers old. She received more thn 10 weekly cryotherpy sessions, ut the lesion did not respond. After 3 PDL sessions the lesion disppered (Fig. 5), nd recurrence hs not een seen in 4-month postopertive follow-up period. Cse 4 A 32-yer-old mle noticed virl wrts in the right nd left hllux, nd the left middle finger when he ws 28 yers old. He received cryotherpy every 2 weeks nd took herl medicine for 3 yers, ut the lesion filed to respond. These lesions were then treted with the CO2 lser, ut tretment filed. After 2 PDL sessions the lesions disppered (Fig. 6), nd did not repper during 2-yer postopertive follow-up period. Discussion The nturl history of verruc vulgris is extremely vrile from one ptient to nother. J. Berth-Jones et l. reported the chnce of cure ws inversely relted oth to the length of history nd to the dimeter of the lrgest wrt 13). Wrt type 5) 10) is lso fctor which cn influence the response rte. Mny different methods hve een used in the tretment of wrts ut tret- 34 Tniguchi, Y ET AL

ing verruc vulgris is therpeutic chllenge with recidivism rte. A reclcitrnt wrt is defined s lesion which hs een present for more thn 6 months nd which hs een treted t lest once without success. Reclcitrnt wrt tretment is more difficult nd often frustrting for oth ptient nd clinicin. In 1993, Tn OT et l. pulished study of 39 ptients with reclcitrnt verruc vulgris who were treted with PDL 12). Recently, severl reserchers hve discussed the effectiveness nd sfety of PDL tretment for use in reclcitrnt verruc vulgris therpy 4)5)8)10)11), ut the response rtes tht hve een reported hve een very vrile. Some reserchers discussed severl fctors dominting the response rte. High energy 5) 8) 10), multiple pulse technique 8) 10), fst repetition rte 8), nd shortening the tretment intervl 8) 10) were the fctors contriuting significntly to higher wrt response rtes. The site of wrts ws lso the fctor influencing the response rte. Prk HS et l. reported the clernce rte of plntr wrts s 47.6%, which ws interior to tht of flt wrts nd periungul wrts 5). The virl wrts we treted with PDL were reclcitrnt. Especilly in cse 1, the plntr lesion ws very old nd very lrge. In ll of the cses reported herein, nd others in the present study, complete cure of the lesions ws extremely difficult, nd ll ptients hd consulted other doctors efore they cme to our clinic, lmost ll of whom hd given up treting the lesion with conventionl methods. Even in the cse of the most severe lesions, we could tret them stisfctory with PDL. The lesion ecme smller nd smller every session, without scr formtion, infection, or secondry hyperpigmenttion chnges. Furthermore, PDL irrdition hs high selectivity for tissue dmge, so the postirrdition pin is more tolerle thn in the cse of the other destructive gents. In point of fct, the PDL tretment did not ffect the working schedules or ctivities of dily life of ny of the sujects in the present study. The mechnism of ction is uncler, ut Kenton- Smith J et l. reported it might e result of virl inctivtion y het, ctivtion of the immunologic process nd removl of the lood supply to the wrt. 14) The wvelength of the 595 nm PDL is found in the yellow light spectrum, which is preferentilly sored in hemogloin nd oxyhemogloin. Wrts contin dilted, congested lood vessels in the derml ppille extending long the rete ridges. 15) Oxyhemogloin within the red corpuscles in the derml cpillries preferentilly sors this yellow light leding to selective photothermolytic microvsculr destruction. 14) Het is developed during the sorption of light y the corpuscles. Intense heting of the derml vessels possily results in collterl dmge of virlly infected kertinocytes nd olitertion of the nutrient supply. 12) Although the photoimmunomodultory process ssocited with PDL tretment hs not een discussed, we suggest tht the inflmmtory response which influences the course of wound heling my further enhnce the utoimmunologicl response, leding to virl inctivtion. We suggest tht dmge to the virlly infected kertinocytes nd olitertion of the nutrient supply represent photothermlly-medited dmge ssocited with the High rective Level Lser Tretment (HLLT) effect of the PDL em in trget tissue, nd the immunologicl response enhnced y the inflmmtory response is n therml nd trumtic LLLT effect on photoiomodulted cells t the periphery of the treted lesion. LLLT my lso e responsile for the decresed pin nd scr formtion. In the tretment of wrts with PDL, HLLT nd LLLT occur simultneously. We cll this coincident dulity of therml dmge nd therml stimultion uto-simultneous lser tretment. The conditions which re desired in the tretment of virl wrts re sfety nd high efficiency, together with the control of pin nd prophylxis ginst hypertrophic scrring. Reclcitrnt wrts often ecome ig. As the size of the wrt increses, the pin during nd fter tretments ecomes stronger. Strong nd reclcitrnt pin is mjor prolem, ecuse the pek incidence of wrt formtion occurs in young dulthood, nd reclcitrnt severe pin cn disrupt ctivities of dily living, including work. LLLT is effective to reduce pin nd contriute to economic effect s result. Conclusions PDL tretment is effective in the tretment of reclcitrnt virl wrts from the points of cure rte, sfety, pin reduction, nd economic effect. We suggest the phenomenon of PDL tretment reltes to oth of therml dmge nd therml stimultion, nd we cll this coincident dulity uto-simultneous lser tretment. The LLLT effect contriutes to the cure rte, the evidence of low incidence of side effects, pin control, nd economic effect. PDL tretment s uto-simultneous lser tretment my e more cceptle tretment thn others. LT FOR RECALCITRANT VIRAL WARTS 35

References 1: Rowson KEK, Mhy BWJ (1967): Hummn ppov (wrt) virus. Bcteriol Rev, 31:110~131. 2: Rook A, Svin JA, Wilkinson DS: The prevlence, incidence nd ecology of diseses of the skin. In: (Rook A, Wilkinson DS, Eling FGJ, Chmpion RH, Burton JL, eds.) Textook of dermtology 4 th edn., Vol 1. 1986, Blckwell Scientific Pulictions, Oxford. Pp39~53. 3: Keefw M, Dick DC (1989): An dult of wrt tretment in Scottish dermtology deprtment. Helth Bull, 47:13~20. 4: Ulrike S, Wolfgng G, Stefn H, Hns MO (2008): Pulsed dye lser tretment is effective in the tretment of reclcitrnt virl wrts. Dermtologic surgery, 34:67~72. 5: Prk HS, Choi WS (2008): Pulsed dye lser tretment for virl wrts: study of 120 ptients. The Journl of Dermtology, 35(8):491~498. 6: Psseron T, Sen K, Mntoux F, Lcour JP, Ortonne JP (2007): 595nm pulse dye lser therpy for virl wrts: single-lind rndomized comprtive study versus plceo. Annles de dermtologie et de venereologie, 134(2):135~139. 7: Komericki P, Akkilic M, Koper D (2006): Pulsed dye lser tretments of genitl wrts. Lsers in surgery nd medicine, 38(4):273~276. 8: Arielle NBK, Roy GG (2001): Pulsed-dye lser versus conventionl therpy in the tretment of wrts. Journl of the Americn Acdemy of Dermtology, 151. 9: Ajy J, Gregory SS (1997): Effectiveness of the 585nm Flshlmp-pulsed tunle dye lser (PTDL) for tretment of plntr verruce. Lsers in surgery nd medicine, 21:500~505. 10: Kristi JR, Nncy MC, Kolleen LK, Dip SP, Clrence DK, Michel JO, Christopher JA (2000): Pulsed-dye lser versus conventionl therpy in the tretment of wrt: A prospective rndomized tril. Journl of the Americn Acdemy of Dermtology, 43(2):275~280. 11: Ellen J, Reecc M, Sen M (1997): Pulsed dye lser efficcy s initil therpy for wrts nd ginst reclcitrnt verruce. Cuitis, 59:206~208. 12: Tn OT, Hurwitz RM, Stfford TJ (1993): Pulsed dye lser tretment of reclcitrnt verruce; primry report. Lsers in surgery nd medicine, 13:127~137. 13: Berth-Jones J, Hutchinson PE (1992): Modern tretment of wrts: cure rtes t 3 nd 6 months. British Journl of Dermtology, 127:262~265. 14: Kenton-Smith J, Tn ST (1999): Pulsed dye lser therpy for virl wrts. British journl of plstic surgery, 52:554~558. 15: Lever WF, Schumerg-Lever G (1983): Disese cused y virus. In: (Lever WF, Schumerg-Lever G) Histopthology of the skin. 1983, JB Lippincott compny, Phildelphi. Pp 371~376. 36 Tniguchi, Y ET AL