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Cryotherapy Versus Podophyllin in the Treatment of Genital Wart ﻣﻘﺎﻳﺴﻪ

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Cryotherapy Versus Podophyllin in the Treatment of Genital Wart ﻣﻘﺎﻳﺴﻪ Cryotherapy versus Podophyllin in the Treatment of Genital Wart Authours: Pouran Layegh* Assistant Professor of Dermatology, Qaem Hospital, Mashad University of Medical sciences Fakhrozaman Pezeshkpoor Assistant Professor of Dermatology, Qaem Hospital, Mashhad university of Medical Sciences Parisa Emam-gholy Tabar Malakshah Assistant of Dermatology, Qaem Hospital, Mashhad university of Medical Sciences Mohammad Taghi Shakeri Assistant Professor of Medical Statistics Division, Community Medicine Department . Mashhad university of Medical ﺗﺎرﻳﺦ اراﺋﻪ : 21/2/85 ﺗﺎرﻳﺦ ﭘﺬﻳﺮش : 86/5/1 ﻣﻘﺎﻳﺴﻪ ﺳﺮﻣﺎدرﻣﺎﻧﻲ ﺑﺎ ﭘﻮدوﻓﻴﻠﻴﻦ در درﻣﺎن زﮔﻴﻞ ﺗﻨﺎﺳﻠﻲ ﺧﻼﺻﻪ ﻣﻘﺪﻣﻪ: زﮔﻴﻞ ﺗﻨﺎﺳﻠﻲ ﻳﻜﻲ از ﺑﻴﻤﺎرﻳﻬﺎي ﺷﺎﻳﻊ ﻣﻨﺘﻘﻠﻪ از راه ﺟﻨﺴﻲ اﺳﺖ ﻛﻪ ﺗﻮﺳﻂ وﻳﺮوس ﭘﺎﭘﻴﻠﻮﻣﺎي اﻧﺴﺎﻧﻲ اﻳﺠﺎد ﻣﻲ ﺷﻮد. ﭘﻮدوﻓﻴﻠﻴﻦ ﻋﺼﺎره ﮔﻴﺎﻫﻲ اﺳﺖ ﻛﻪ از دﻳﺮ ﺑﺎز در درﻣﺎن زﮔﻴﻞ ﺗﻨﺎﺳﻠﻲ ﻣﻮرد اﺳﺘﻔﺎده ﻗﺮار ﻣﻲ ﮔﺮﻓﺘﻪ اﺳﺖ. اﻳﻦ دارو ﺧﺎﺻﻴﺖ ﺟﻠﻮﮔﻴﺮي ﻛﻨﻨﺪه از ﺗﻘﺴﻴﻤﺎت ﺳﻠﻮﻟﻲ (آﻧﺘﻲ ﻣﻴﺘﻮﺗﻴﻚ) داﺷﺘﻪ و اﺛﺮ ﻣﺴﺘﻘﻴﻤﻲ ﺑﺮ ﺳﻠﻮﻟﻬﺎي اﭘﻲ ﺗﻠﻴﺎل دارد. از ﻃﺮﻓﻲ ﻧﻴﺘﺮوژن ﻣﺎﻳﻊ ﻛﻪ ﻣﺎده اي اﺳﺖ ﻛﻪ ﺑﻄﻮر وﺳﻴﻊ در ﺳﺮﻣﺎ درﻣﺎﻧﻲ (ﻛﺮاﻳﻮﺗﺮاﭘﻲ) اﺳﺘﻔﺎده ﻣﻲ ﺷﻮد، ﻣﻮﺟﺐ ﻣﺮگ ﺳﻠﻮﻟﻲ، اﻳﺠﺎد ﻛﺮﻳﺴﺘﺎﻟﻬﺎي ﻣﺎﻳﻊ در داﺧﻞ ﺳﻠﻮل و آﺳﻴﺐ اﺟﺰاي آن ﻣﻲ ﮔﺮدد. اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﺎ ﻫﺪف ارزﻳﺎﺑﻲ اﺛﺮ ﺑﺨﺸﻲ ﻣﺤﺼﻮل ﭘﻮدوﻓﻴﻠﻴﻦ ﺑﺎ ﺳﺮﻣﺎ درﻣﺎﻧﻲ ﺑﺎ ﻧﻴﺘﺮوژن ﻣﺎﻳﻊ در درﻣﺎن زﮔﻴﻞ ﻫﺎي ﺗﻨﺎﺳﻠﻲ اﻧﺠﺎم ﺷﺪه اﺳﺖ. روش ﻛﺎر: اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻛﺎرآزﻣﺎﻳﻲ ﺑﺎﻟﻴﻨﻲ، از ﺑﻬﻤﻦ 1382 - دي ﻣﺎه 1384 در درﻣﺎﻧﮕﺎه ﭘﻮﺳﺖ ﺑﻴﻤﺎرﺳﺘﺎن ﻗﺎﺋﻢ (ﻋﺞ)، ﺑﺮ 70 ﺑﻴﻤﺎر ﻣﺒﺘﻼ ﺑﻪ زﮔﻴﻞ ﺗﻨﺎﺳﻠﻲ اﻧﺠﺎم ﺷﺪ. 35 ﺑﻴﻤﺎر ﺑﻪ ﻃﻮر ﺗﺼﺎدﻓﻲ ﻣﺤﻠﻮل ﭘﻮدوﻓﻴﻠﻴﻦ درﻳﺎﻓﺖ ﻛﺮده و 35 ﻧﻔﺮ ﺗﺤﺖ درﻣﺎن ﺑﺎ ﻛﺮاﻳﻮﺗﺮاﭘﻲ ﺑﺎ ﻧﻴﺘﺮوژن ﻣﺎﻳﻊ ﻗﺮار ﮔﺮﻓﺘﻨﺪ. ﻣﺼﺮف دارو ﻫﻔﺘﻪ اي ﻳﻚ ﺑﺎر ﺗﺎ ﭘﺎك ﺷﺪن ﻛﺎﻣﻞ ﺿﺎﻳﻌﺎت و ﻳﺎ ﺣﺪاﻛﺜﺮ دوره 8 ﻫﻔﺘﻪ اي اداﻣﻪ داﺷﺖ. ﺳﭙﺲ ﺑﻴﻤﺎران ﺗﺎ ده ﻫﻔﺘﻪ از ﻧﻈﺮ اﺣﺘﻤﺎل ﻋﻮد ﻣﺠﺪد ﭘﻴﮕﻴﺮي ﻣﻲ ﺷﺪﻧﺪ. ﻧﺘﺎﻳﺞ: زﻣﺎن ﻣﺘﻮﺳﻂ ﺑﻬﺒﻮد ﻛﺎﻣﻞ ﺿﺎﻳﻌﺎت 9/3 ﻫﻔﺘﻪ (1- 7 ﻫﻔﺘﻪ) ﺑﺮاي ﭘﻮدوﻓﻴﻠﻴﻦ و 9/4 ﻫﻔﺘﻪ (1 - 9 ﻫﻔﺘﻪ) در ﮔﺮوه ﺳﺮﻣﺎ درﻣﺎﻧﻲ ﺑﻮد (p=0/039). از ﻣﻴﺎن ﺑﻴﻤﺎران دو ﮔﺮوه ﻛﻪ ﺑﻪ ﻃﻮر ﻛﺎﻣﻞ درﻣﺎن ﺷﺪه ﺑﻮدﻧﺪ و ﻳﺎ آﻧﻬﺎ ﻛﻪ دوره 10 ﻫﻔﺘﻪ اي ﭘﻴﮕﻴﺮي ﺷﺎن ﺑﻪ ﺳﺮ رﺳﻴﺪه ﺑﻮد 26% و 47% ﺑﻪ ﺗﺮﺗﻴﺐ در دو ﮔﺮوه ﭘﻮدوﻓﻴﻠﻴﻦ و ﺳﺮﻣﺎ درﻣﺎﻧﻲ ﻋﻮد را ﺗﺠﺮﺑﻪ ﻧﻤﻮدﻧﺪ (p<0/05). واﻛﻨﺸﻬﺎي اﻟﺘﻬﺎﺑﻲ ﻣﻮﺿﻌﻲ ﺑﻪ ﻃﻮر ﻗﺎﺑﻞ ﺗﻮﺟﻬﻲ در ﮔﺮوه ﺳﺮﻣﺎ درﻣﺎﻧﻲ ﺑﻴﺸﺘﺮ از ﭘﻮدوﻓﻴﻠﻴﻦ ﺑﻮد. ﻧﺘﻴﺠﻪ ﮔﻴﺮي: ﻃﺒﻖ ﻧﺘﺎﻳﺞ ﺑﻪ دﺳﺖ آﻣﺪه ﻣﺤﺼﻮل ﭘﻮدوﻓﻴﻠﻴﻦ در درﻣﺎن زﮔﻴﻞ ﺗﻨﺎﺳﻠﻲ ﻣﻮﺛﺮ ﺑﻮده و ﻋﻮارض و اﺣﺘﻤﺎل ﻋﻮد ﻛﻤﺘﺮي ﻧﺴﺒﺖ ﺑﻪ ﻛﺮاﻳﻮﺗﺮاﭘﻲ ﺑﺎ ﻧﻴﺘﺮوژن ﻣﺎﻳﻊ دارد. ﻛﻠﻤﺎت ﻛﻠﻴﺪي: ﺳﺮﻣﺎ درﻣﺎﻧﻲ، ﭘﻮدوﻓﻴﻠﻴﻦ، زﮔﻴﻞ ﺗﻨﺎﺳﻠﻲ Address: Department of Dermatology, Qaem Hospital, Mashhad University of Medical Sciences Tel: +98511 8814988 Fax: +985118409612 E-mail: Pouran_layegh @yahoo.com 133 Introduction The purpose of this study was to evaluate the Genital human papilloma virus (HPV) efficacy of podophyllin solution versus liquid ♦ infection is probably one of the most nitrogen cryotherapy on genital warts. Pouran Layegh, MD, et al MD, Pouran Layegh, common infections that can be sexually transmitted. More over, because of its clear Material and Methods association with cervical cancer in women This prospective clinical trial was performed and its potential association with other from February 2003 to December 2005 in anogenital malignancies it is an important Dermatology Clinic of Qaem Hospital, public health problem (1, 2). Mashhad university of Medical Sciences. A It has been estimated that 30% to 50% of total of 70 female patients with external sexually active adults have genital human genital wart entered the trial. The diagnosis of papiloma virus (HPV) infection and 1% have genital warts was established by physical genital wart (3). examination and confirmed by histopathology Patients are often asymptomatic but may have when indicated. Only clinically visible, discomfort, discharge or bleeding. The external anogenital warts were evaluated and typical anogenital wart is soft, pink, treated. The wart area was determined by elongated, and sometimes filliform or measuring the two greatest perpendicular pedunculated. The lesions are usually dimensions of each wart and taking the multiple especially on moist surfaces and product of these two measurements. Total their growth can enhance during pregnancy wart area was the sum of areas for each wart. (4) or in the presence of other local infections The patients divided randomly into two (5, 6). groups. Those who had documented Genital wart may clear without therapy. This is hypersensitivity, diabetes, impaired thought to be mediated by immunologic peripheral circulation, total lesion area > 400 responses (7). mm², any individual lesion with an area of A variety of treatment methods are available for >100mm², intrameatal or vaginal warts, or if genital wart. Podophyllin is a plant derived being pregnant were excluded. A solution of resin containing several cytotoxic compounds. 25% podophyllin in compound tincture of It is more effective on mucosal than keratinized benzoin was applied accurately and in enough surfaces. It acts as an anti-mitotic, disrupting amounts to cover the wart area, then allowed the formation of the spindle on which to dry for a few minutes and washed out after chromosomes align at mitosis. Podophyllin 4 hours. In cryotherapy, cotton wool was resin is used as solution of 10-25% in dipped in the liquid nitrogen and applied to compound tincture of benzoin for treatment of wart area for two short freeze – thaw cycles, genital wart. Podophyllin is generally being held until a white halo area appeared ineffective if applied to wart of other types (8). around the circumference of the lesion (about Liquid nitrogen is most widely used as the 10 to 20 seconds). In both groups treatment cryotherapy agent because of its easy usage, was repeated weekly and continued until inexpensiveness and readily availability to complete clearing of lesions or for a very low temperature (-196); it also works maximum treatment period of 8 weeks. In faster than other methods. each visit, the wart evaluation and skin The extent of injury is determined by the rate of irritation assessed, so patients were queried freezing, the coldest temperature reached, the regarding adverse events and concomitant freeze time, and the rate of thawing. Maximum medications as well as pain, itching and damage reduction is made by rapid freezing and burning at the site of agent application or slow thawing; repeating the freeze cycle adjacent area. During each visit they were reduces greater tissue damage (9). asked to quantify these symptoms as mild, moderate or severe. Patients who experienced 134 complete clearance of warts, during the In podophyllin group 3 patients and in treatment period, entered a free follow up cryotherapy group 6 patients had history of treatment for a period of 10 weeks (or less if previous genital wart, also 6 patients in no recurrence was noted). podophyllin group and 5 patients in Data entry and coding was done and it was cryotherapy group had history of previous analyzed by SPSS version 9. Student t-test, χ² nongenital wart and 2 patients in each group test and mann-withney were used for the had history of previous herpes genital statistical analysis. Statistical significance infection. Number of warts and baseline wart was defined as p<0.05. area in podophyllin and cryotherapy group were 9.7 (range 9-20), 101 mm² (range15- Results 385) and 9.5 (range 3-16), 328 mm² (11-234), From the total of 70 patients who entered the respectively. trial, only 59 female patients completed the The commonest presentation of wart were trial (11 patients who, discontinued for papule in 21 and 19 patients of podophyllin personal reasons, judged to be noncompliant and cryotherapy groups respectively. Cryotherapy vs. Podophyllin in Genital Wart Genital in Podophyllin vs. Cryotherapy with dosing schedules or failed to follow-up However only one patient in each group had condyloma acuminatae. The most common ♦ were excluded from the analysis). There was no significant difference between two groups sites of lesions were perineum (23 patients), with regard to the age. The mean age of vestibule (22 patients) and least common sites podophyllin group was 25/6 years (range of were inguinal (55 and 56 patients in 17-47 years) and cryotherapy grouping 25/5 podophyllin and cryotherapy group years (range of 16-37 years). Of patients 22 respectively) (Table 1). were single and partner of 32 were affected. Table 1: Site of wart lesions in two groups of patients, in Dermatology Clinic of Qaem Hospital, Mashhad, Feb 2003 to Dec 2005 Site of wart Podo phyllin Crytherapy Chi-squre test Mons publis 18 19 0.62 Labia major 8 12 0.45 Prineum –vestibule 23 22 0.17 Labia minor 13 16 0.72 Vagina orifice 12 13 0.25 Perianal 12 11 0.97 Inguinal 5 6 0.60 Thigh 11 5 0.12 The mean duration of wart before therapy for The mean duration of complete clearance was podophyllin and cryotherapy groups was 4.7 3.9 weeks (range of 1-7) for podophyllin and weeks (range of 1-12) and 4.3 weeks (range 4.9 weeks (range of 1-9) for cryotherapy of 1-12), respectively. groups (p=0.039) (Fig1). 135 70 60 50 40 Cryo 30 Podo 20 Median percent reduction 10 0 012345678 Treatment week Figure 1: Median percentage reduction in baseline wart area in both groups. In Dermatology Clinic of Qaem Hospital, Feb 2003 to Dec 2005 Adverse reactions of two regimens are showed in Table 2. Table 2: Application – site reactions and intensity, in Dermatology Clinic of Qaem Hospital, Mashhad, Feb 2003 to Dec 2005 Incidence Incidence for Sign or for cryo podophyllin Intensity of reaction Intensity of reaction p.value symptoms therapy therapy group group mode Mild moderate Severe mild severe rate Pain 6 5 1 0 18 16 2 0 *0.001 Itching 26 23 3 0 15 14 1 0 *0.012 Burning 29 23 6 0 28 18 8 2 *0.074 Erosin 5 0 0 0 9 0 0 0 **0.14 Erythema 8 0 0 0 12 0 0 0 **0.16 *Mann whitney test ** Chi –square At the end of treatment overall side effects abstinence from intercourse or usage of were more frequent in cryotherapy.
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