COMPARATIVE EVALUATION OF EFFICACY OF TOPICAL SALICYLIC ACID OINTMENT AND 5-FLUOROURACIL CREAM IN WARTS PATIENTS

There are various modalities used for the of warts. Very few studies have been done which compare the efficacy of topical salicylic acid and


…………………………………………………………………………………………………….... Introduction:-
Warts are benign epithelial proliferation of skin and mucosa caused by human Papilloma virus 1 . Human Papilloma viruses (HPV) is species specific, undeveloped, double stranded DNA virus, belonging to Papovaviridae family 2 . It affects almost every part of skin, genital and oral mucosa 3,4 . The incubation period of wart is variable between few weeks to few years 5,6 . Subclinical infection may occur during early childhood leading to development of cell mediated immunity 7,8 . The management of warts may be with topical podophyllin, bleomycin, with 5-Fluorouracil, with imiquimod, formaldehyde, gluteraldehyde, cidofovir and keratolytics 9,10 . The combination of topical 5-Fluorouracil and salicylic acid has a synergistic effect on the warts which is due to the anti-proliferative effect of the 5-Fluorouracil and keratolytic effect of the salicylic acid 11,12 . There are only a few studies done for these modalities. Therefore, this study has been intended to determine the efficacy of topical 16 %salicylic acid ointment and 5% 5-Fluorouracil cream in warts patients.

Material and Methods:-
As per the sample size formula (sample size= Z 2 PQ/M 2 where, Z = 1.96 at 95 % confidence interval, P is the prevalence of warts in India 13 , i.e. P = 0.2 (20%), Q is 1-P, i.e. Q = 0.80 and M is margin of error. Minimum sample size with 5% margin of error (precision) was 245.86. So, total 300 clinically diagnosed patients of warts were enrolled from outpatient department of Dermatology, M.R.A. Medical College, Ambedkar Nagar. Patients of warts were divided into three groups based on the modalities of treatment. Patients fulfilling inclusion criteria after taking informed consent were selected for study. Ethical approval was taken from institutional ethical Committee.

Type of study:
Completely randomized design Inclusion criteria: Diagnosed cases of warts on trunk and extremities with age of 18 to 50 years from Ambedkar Nagar or around.
Exclusion criteria: Subjects with warts on face, scalp and genital areas, pregnant and lactating women, patients under immunosuppressive therapy and other systemic diseases were excluded from the study.

Pre-treatment workup:
Clinical history: A detailed history of the patient was taken regarding name, age, sex, occupation, total duration of disease, site, history of trauma etc.
Clinical examination: Patients were examined in day light. A routine dermatological examination was done. The variants of the warts were noted and morphological details of the lesions in terms of number, site, size and its distribution over the body were recorded. Consent: Proper written consent was taken from each individual explaining the drugs, possible outcomes and complications.

Treatment modalities given:
Patients were instructed to soak the warty area by putting wet towel on it for 5-10 minutes and then remove the upper dead layer of the warts by gentle scrubbing. This was done in the morning and at bedtime. Timings of application of different modalities were as following 1. Modality I: In this modality 16% salicylic acid was applied daily in the morning and at bedtime. 2. Modality II: In this modality 5% 5-Fluorouracil was applied daily in the morning and at bedtime. 3. Modality III: In this modality 5% 5-Fluorouracil was applied daily in the morning and 16% salicylic acid was applied at bedtime.
Criteria for successful therapy: The evaluation of therapy was based on complete regression of lesion, absence of recurrence of treated lesion after 3 months follow up (All the patients were followed up once a week up to four weeks then once in two weeks for next eight weeks. After completion of first three months of study all the patients were followed every month for any recurrence of illness for next three months). Responses of all treatment modalities were assessed by the measurement of reduction in the average volume of warts on subsequent follow up.
Warts volume was calculated by measuring maximum and minimum diameter of the lesions using formula πr 2 h (where r denotes the radius and h denotes height of the wart while value of π is 22/7). The diameters of the warts were measured by using divider and the corresponding gap was interpreted on horizontal scale while height was measured directly using vertical scale. Then average volume of the warts was calculated as the sum of volumes of all warts divided by number of warts.
Statistical method used: After collecting the information, data was compiled, tabulated and sort out in SPPS version 23. The variables were presented as mean ± standard deviation. Categorical variables were presented as percentage.
One way Anova test was applied to compare the significance of difference in continuous variables. A P-value < 0.05 was considered as statistically significant for statistical tests.

Results:-
Total 300 clinically diagnosed patients of warts were enrolled in this study and 16 were lost during follow up. Out of 300 warts patients, 168 (56%) were male and 132 (44%) were female. Other socio-demographic characteristics were shown below (Table-1).
Outcome assessment: 99.95 % clearance was seen in warts volume at 12 weeks of treatment using Modality III, followed by Modality I (99.67% clearance in warts volume) and Modality II (99.31% clearance in warts volume) which were statistically significant at p value <0.01 level (shown in Table-3 and figure-1) by using one One way Anova test for significant difference between groups.
Cure according to Modalities: Very good response was seen with all modalities but among them Modality III (5% 5-Fluorouracil was applied daily in the morning and 16% salicylic acid was applied at bedtime) was excellent for warts patients.  Skin markings/dermatoglyphics: After 12 weeks of treatment, 235 (78.33%) patients had complete reappearance of normal skin marking or dermatoglyphics. Maximum complete reappearance of normal skin was seen with modality III treatment (Figure no.-2).
Adverse effects: Minimum adverse effects were seen with modality III treatment in warts patients followed by modality II and modality I (Table-2).

Discussion and conclusions:-
HPVs can infect and cause disease at any site in stratified squamous epithelium, either keratinizing (skin) or nonkeratinizing (mucosa). The clinical problems encountered with such infections can be broadly divided into cutaneous warts, genital warts, oral warts and laryngeal warts 14 16 . Contrary to our finding, Rulison and Coles found that warts were more common in women than men 17,18 . Various researchers had shown that the prevalence of warts were more in male than female [19][20][21][22] . In the present study, the majority of wart patients were from rural areas. This can be explained by the fact that the rural population is more prone to trauma due to involvement in agricultural work. This can also be attributed to the dominance of agricultural workers and laborers in our study. Warts were more prevalent in people who were illiterates and having qualification of high school. In our study, Common wart was the most common variant (51.33%), followed by flat warts (20.67%), plantar wart (20%) and periungual warts (8%). Similar result was reported by various scientists 20,21 .
In the present study, 16% salicylic acid treatment was successful in warts patients with 99.67% recovery from warts. Similar result has been reported by various research studies [23][24][25] . One of the studies in Southern Illinois University School of Medicine, Springfield, Illinois, USA found that Salicylic acid is one of the most commonly used treatments for warts 26 . There is consistent evidence that topical salicylic acid is an effective therapy for cutaneous warts. In Japan, a systematic review of local treatments of cutaneous warts found evidence that topical treatments with salicylic acid have a therapeutic effect, with a cure rate of 75 % 27 . In present study, out of 100 patients, 5% 5-Fluorouracil treated 92 patients had 99.31% recovery from warts. One of the study conducted by Botacini et al., found that 5-Fluorouracil can be a good option for treatment 28 . There is consistent evidence to support that the 5% 5fluorouracil cream could completely eradicate all plantar warts within 12 weeks of treatment 29 . Similarly, Goncalves reported 50% cure rates for common warts after 5-Fluorouracil therapy 30 . In present study, modality III (combination of 5-Fluorouracil and 16% salicylic acid) cured 96 patients had shown 99.95 % recovery from warts. In Germany, the Systematic literature review and meta-analysis had shown similar finding that combination of 5fluorouracil and 16% salicylic acid was an efficient and valuable remedy for common and plantar warts over 5-Fluorouracil or 16% salicylic acid alone 31 . One of the medical record reviews which was conducted in New York, USA also proved that the twice-daily applications of 5% topical 5-fluorouracil combined with topical 16% salicylic acid is a safe and effective treatment for warts with complete clinical resolution in all patients 32 . Combination of 5-Fluorouracil and 16% salicylic acid is best for the treatment of warts with maximum recovery from warts with minimum adverse effect over 5-fluorouracil or 16% salicylic acid alone.

Limitation of the Study:
This study had been conducted on small sample size so need more sample size for more elaborated study. It was very difficult to maintain follow up of same patients. Some of patients may lose during follow up.