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ORIGINAL ARTICLE
Year : 2007  |  Volume : 52  |  Issue : 2  |  Page : 96-98
Evaluation of the efficacy of 50% citric acid solution in plane wart treatment


Department of Dermatology, Isfahan University of Medical Sciences, Alzahra Hospital, 81744, Isfahan, Iran

Correspondence Address:
Anahita Vali
Bolvar of Sofeh, Alzahra Hospital, PO Box 775, Isfahan, 81744
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.33287

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   Abstract 

Background and Aims: Treatment of plane warts is problematic, methods such as cryotherapy and cauterization is associated with high recurrence rate, risk of scar, pain and high cost. Topical tretinoin causes irritant contact dermatitis that limited its use. Citric acid was used in treatment of warts in traditional medicine of Iran. We evaluated the efficacy of 50% citric acid solution in water in treatment of plane warts and compared it with 0.05% tretinoin lotion.
Materials and Methods : This study was a double blind; prospective, case-control study.Seventy-five patients with bilateral plane warts who signed informed consent were included. Exclusion criteria were pregnancy, breast-feeding, suffering from any systemic disease and the use of any other drug due to treatment of warts in past six weeks. The patients randomly used citric acid or Tretinoin lotion to lesions at each side of the body. Randomization was performed by coin-flipping.
Patients were examined at three weeks interval for six weeks and number of warts were recorded in the proforma, which included the name, sex, address and code of the drug that was used in each side of the body and side effects. The results were analyzed by Chi-square test statistically. Results: After six weeks 64.4% of the lesions in citric acid treated group disappeared versus 53.7% of the lesions in tretinoin treated group. This difference was significant ( P value Conclusion: On the basis of this study, the treatment of plane warts by 50% citric acid is strongly suggested. This modality is superior to tretinoin lotion due to higher efficacy and low incidence of side-effects and lower cost.


Keywords: Citric acid, drug-therapy, tretinoin, wart


How to cite this article:
Vali A, Ferdowsi F. Evaluation of the efficacy of 50% citric acid solution in plane wart treatment. Indian J Dermatol 2007;52:96-8

How to cite this URL:
Vali A, Ferdowsi F. Evaluation of the efficacy of 50% citric acid solution in plane wart treatment. Indian J Dermatol [serial online] 2007 [cited 2019 Apr 23];52:96-8. Available from: http://www.e-ijd.org/text.asp?2007/52/2/96/33287



   Introduction Top


Warts are benign proliferations of the skin and mucosa that result from infection with papillomaviruses. Flat warts or verruca plana are 2 to 4 mm, slightly elevated, flat-topped papules that have minimal scale. These are most frequent on the face, hands and lower legs. Widespread flat warts occurs in patients with epidermodysplasia verruciformis (EV) that are usually caused by the same human papilloma virus (HPV) types as those found in flat warts in the general population (e.g., HPV 3, 10, 28 and 49). [1]

Treatment of warts is a good idea because each lesion could be a source or reservoir for HPV and therapy will reduce the risk of spreading infection to the other parts of the body of the same patient and to the others. [2] Non-pharmacological techniques include surgical excision, electrocauterisation or laser therapy. Cryotherapy may be performed with liquid nitrogen or solid carbon dioxide. Chemical destruction with acids (acetic acid, lactic acid, nitric acid, salicylic acid or trichloroacetic acid), silver nitrate, potassium hydroxide, formaldehyde or glutaral or podophyllum resin or its derivatives (podophyllotoxin) are possibly used more frequently than other forms of drug-therapy in anogenital warts. Intralesional injection of cytotoxics such as bleomycin or fluorouracil also destroys the wart and may be employed in severe or resistant cases. Fluorouracil may also be applied topically. Tretinoin has been tried topically for its effects on epidermal growth. Interferons have antiviral, antiproliferative and immunomodulatory actions and have been thus investigated in the management of warts; some studies, especially those involving intralesional administrations, have demonstrated benefit. Imiquimod has been recently introduced for the topical treatment of anogenital warts. Other drugs with immunomodulatory effects, such as cimetidine, have been tried in a few patients. There are also small studies of treatment with diphencyprone, a contact sensitizer and photodynamic therapy using 5-aminolaevulinic acid. [3]

Pain, inconvenience and risk or scarring is associated with routine treatment methods such as caustics and acids application, cryotherapy and electrocautery. [1] These problems are more in patients with face involvement due to cosmetic and psycho-social aspects of this area. All current treatments have about 50% complete response rate and 25-50% recurrence rate. [4] Retinoic acid may be applied topically in plain wart, although the best results are claimed for higher than usual concentration and irritation is common. [5]

Lemon essence was used in traditional medicine of Iran as wart treatment. The effective material of lemon juice is citric acid. [6] Citric acid is an organic acid, which are used as food additive to increase the acidity in foods or to enhance the absorption of non-hem iron. [7] Citric acid is used in effervescing mixtures. Preparations containing citric acid are used in the management of dry mouth and to dissolve renal calculi. [6] The aim of this study was evaluation of the efficacy of citric acid in treatment of warts and comparison of it with tretinoin.


   Materials and Methods Top


Seventy-five consecutive patients were seen in the outpatient clinics with the diagnosis of plane wart and involvement of the two sides of the body was included in this double blind intrapatient comparison. Patients with systemic disease such as diabetes mellitus, asthma, renal insufficiency or patients who consume immunosuppressive drugs such as cases with renal transplants, pregnant and nursing women were excluded from the study. All patients received full information on the purpose and design of the study and had not received any systemic or topical wart treatment within four weeks before entering the study. For every patient admitted to the study, a detailed history was taken including age, sex, address and number of the lesions in each area of the body and registered in checklist.

In each patient, lesions of one side of the body were treated by application of 50% citric acid aqueous solution and the other side by 0.05% tretinoin lotion, twice daily. Solutions were applied on the lesions by the wood end of a cotton swab to minimize filtration of effective drug by cotton. A parent was applying the solutions on the children who were aged less than ten years.

The side that was treated was randomly selected by a fair coin flipped manner. Both drugs were inside identical tubes, had similar appearance and were marked with a recognition code.

Citric acid solution was prepared from mixing citric acid monohydrate (C6H8O7, H2O, MW=210.14 Bach number: K1338944 Drug Code: 244) with deionized water at temperature 37 centigrade with heteromagnet apparatus.

Treatment duration was planned as six weeks and the control visits were arranged at three weeks intervals. The number of the warts in each side of the body and any adverse effect related to the study preparation such as burning sensation, pruritus, erythema or contact dermatitis were recorded in each visit.

Evaluation of the efficacy of treatment was based on reduction of the number of warts. Statistical analysis was performed by the Chi-square test and value of P <0.05was considered significant.


   Results Top


75 out of 78 patients participated in the entire study. Two patients were excluded due to irregular use of drug and another patient did not come to the follow-up visits. Male to female ratio was 36:29. Distribution of the patients in different age groups is shown in [Table - 1]. Peak of incidence of plane wart was between 11 to 20 years old (45.4%).

The overall numbers of the lesions in each group are shown in [Table - 2]. The overall number of the lesions were 1575. Eight hundred and forty lesions were treated by application of citric acid solution and 735 lesions by tretinoin lotion. After six weeks, number of the warts in citric acid group was 297 versus 340 in tretinoin group. In both groups, clinically significant improvement was noted after six weeks (64.45 in citric acid and 53.7% in tretinoin -treated group). Chi-square test showed that efficacy of citric acid was superior and difference was significant statistically ( P <0.05) but when we compared the onset of action of these modalities, difference was not significantly ( P =0.117). In the other word, we found higher efficacy with citric acid but not shorter duration of treatment.

Tolerability and patient satisfaction with citric acid solution was good. 14.4% of patients in citric acid group complained from burning or stinging sensation, erythema and pruritus versus 22% in tretinoin group. 69.3% of patients were more satisfied from citric acid, 20.3% of cases preferred tretinoin and 10.4% of cases had no preference.


   Discussion Top


Many researchers have studied about plane wart treatment. In a randomized controlled study of 25 children, 85% of warts cleared with 0.05% tretinoin cream compared with 32% in controls. [8] In our study, efficacy of tretinoin was less (53.7%).

Retinoids are involved in the regulation of diverse biologic functions. They affect cell growth and differentiation, morphogenesis tumor promotion and malignant cell growth, exert immunomodulatory action and alter cellular adhesiveness. [9]

Molluscum contagiosum, warts and various forms of icthyosis may be improved by topical retinoids to a variable degree. It has been well-documented that Tretinoin (all-trans retinoic acid) increases proliferation of basal keratinocytes and also the number of cell layers expressing the differentiation markers involucrine, loricrine,fillagrin and epidermal transglutaminase. These epidermal changes collectively translate to clinical desquamation and peeling and mediated by nuclear receptors of retinoids. [10]

Induction of desquamation and immunomodulation may be the probable mechanism that explains the efficacy of tretinoin in plane wart treatment.

Mizuki et al., successfully treated two patients with focal plane wart by topical photodynamic therapy using 5-aminolevulinic acid. [11] Durani B and Jape U reported a case with plane wart that was treated by topical imiquimod 5%. [12]

Anecdotal evidence suggests that lemon extract may treat wart. Our data showed that aqueous solution of citric acid is more effective than tretinoin in treatment of plane wart, with less side effects although the initial response to it is not faster. Citric acid ingested frequently or in large quantities may cause erosion of the teeth and have a local irritant action. [6] Out data showed that the most common side effects of topical application of citric acid were burning and stinging sensation, pruritus, erythema and irritant contact dermatitis that were mild and transient.

What is the mechanism of action of citric acid solution in treatment of plane warts?

Citric acid has keratolytic properties, such as salicylic acid or lactic acid or trichloroacetic acid and even topical retinoids that reduce hyperkeratosis but irritate the skin. [2] Citric acid has disinfecting properties. Lemon juice is used for disinfecting drinking water during epidemics of waterborne enteritis, lemon juice may be a useful alternative to conventional means of sterilizing drinking water. The addition of 2 tablespoons of lemon juice to a liter of water (concentration 2%) destroys  Vibrio cholerae Scientific Name Search  after 30 min (Bull Pan Am Hlth Org 1994 28: 324-30). Higher concentrations are needed if the water is alkaline as it may be if it is from an underground source. The antibacterial effect is due to citric acid and applies only to drinking water-water used for disinfecting vegetables is likely to require a greater concentration. [13]

Diphencyprone is one type of wart treatment that acts by stimulation of immune system. [12] Is it possible that citric acid has immunostimulatory properties? We don't know and other researches are necessary for answering this question. At this point, the most probable mechanism of action of citric acid appears to be keratolytic and disinfecting properties.


   Conclusion Top


Aqueous solution of citric acid appears as an effective, safe and cost-effective treatment in plane wart.

 
   References Top

1.Lowy DR, Androphy EJ. Warts. In : Freedberg IM, Eison AZ, et al . Fitzpatrick's Dermatology in General Medicine, 6 th ed. Mcgraw-Hill Co: New York; 2004. p. 2119-29.  Back to cited text no. 1      
2.Benton EC. Human papillomavirus infection and molluscum contagiosum. In : Harper J, Orange A, Prose N. Textbook of pediatric dermatology, 1 st ed. Blackwell Science: Oxford; 2000. p. 313-6.  Back to cited text no. 2      
3.Sterling JC, Handfield-Jones S, Hudson PM. British Association of Dermatologists. Guidelines for the management of cutaneous warts. Br J Dermatol 2001;144:4-11.  Back to cited text no. 3      
4.Androphy EJ, Beutner K, Olbricht S. Human papillomavirus infection. In : Arndt KA, Leboit PE, Robinson JK, Wintroub BU. Cutaneous medicine and surgery. 1 st ed. Saunders Co: USA; 1996. p. 1112.  Back to cited text no. 4      
5.Sterling JC. Virus infections. In : Burns T, Breathnach S, Cox N, Griffiths C, et al . In : Rook's textbook of dermatology,7 th ed. Blackwell Science: UK; 2004. p. 25.50.  Back to cited text no. 5      
6.Sweetman SC. Martindale: The complete drug reference. 33 rd ed. Pharmaceutical Press: London; 2002. p. 1108, 1596.  Back to cited text no. 6      
7.Southgate DA. Food processing. In : Garrow JS, James WP, Ralph A. Humannutrition and dietics, 10 th ed. Churchill Livingstone Co: UK; 2000. p. 403.  Back to cited text no. 7      
8.Kubeyinje EP. Evaluation of the efficacy and safety of 0.05% tretinoin cream in the treatment of the plain warts in Arab children. J Dermatol Treat 1996;7:21-2.  Back to cited text no. 8      
9.Kuenzil S, Saurat JH. The retinods. In : Freedberg IM, Eison AZ, et al . Fitzpatrick's dermatology in general medicine, 6 th ed. McGraw-Hill Co: New York; 2004. p. 2410.  Back to cited text no. 9      
10.Kans S, Voorhees JJ. Topical retinoids. In : Freedberg IM, Eison AZ, et al . Fitzpatrick's dermatology in general medicine, 6 th ed. McGraw-Hill Co: New York; 2004. p. 2331-3.  Back to cited text no. 10      
11.Mizuki D, Kaneko T, Hanada K. Successful treatment of topical photodynamic therapy using 5-aminolevulinic acid for plain warts. Br J Dermatol 2003;149:1087.  Back to cited text no. 11      
12.Durani BK, Jape U. Successful treatment of facial plain warts with imiquimod. Br J Dermatol 2002;147:1018.  Back to cited text no. 12      
13.Ethics committee approval for German clinical trials. Lancet 1995;345:577.  Back to cited text no. 13      



 
 
    Tables

  [Table - 1], [Table - 2]

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