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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 36  |  Issue : 2  |  Page : 34-38

Oral zinc sulfate in the treatment of recalcitrant warts


Department of Dermatology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission16-May-2016
Date of Acceptance10-Jul-2016
Date of Web Publication21-Mar-2017

Correspondence Address:
Rasha M Genedy
Department of Dermatology, Faculty of Medicine, Alexandria University, 9101 Alexandria
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-6530.202637

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  Abstract 


Background Cutaneous warts are benign papillomas of the skin caused by infection with human papillomavirus. The primary treatment methods of warts are physical destruction. However, these treatments are not suitable for patients with multiple lesions or with fear of pain and scarring. Therefore, immune-modifying agents might be a useful therapeutic alternative because they can be painlessly and easily administrated. Zinc is a trace element that is essential for the functioning of the immune system. It could counteract viral infections. Zinc sulfate is a promising therapy for the management of multiple warts.
Aim The aim of this study was to determine the association of low serum zinc levels with persistent viral warts and to assess whether oral zinc sulfate was effective in treating persistent viral warts.
Patients and methods This randomized case–control clinical trial was conducted on 40 patients. Eligible patients had five or more warts of at least 6-month duration resistant to one or more lines of treatment. Blood samples of all patients were taken to determine basic serum zinc level using spectrophotometry. Patients were randomly divided into two groups; each group consisted of 20 patients. Group I received oral zinc supplementation 10 mg/kg up to 600 mg maximum daily dose for 1 month. Group II did not receive any treatment. All of the patients were instructed not to take any other treatment during the trial. At the end of the study, the patients were assessed and the serum zinc level was remeasured. The percent of improvement of the warts was classified as follows: excellent, greater than 75%; moderate, 75–50%; mild, less than 50%; and no change.
Results At the beginning of the study, the mean serum zinc level in group I was 85.95 μg/dl and that in group II was 81.30 μg/dl. However, at the end of the study, the mean serum zinc level in group I was 115.61±19.69 μg/dl and that in group II was 81.90±36.04 μg/dl. Serum zinc level significantly increased after treatment compared with that before treatment in group I (P=0.013); moreover, it became significantly higher than that in group II (P=0.006). The significant increase in serum zinc level in group I was associated with more clinical improvement in the warts. Shorter duration of the disease was associated with better response. Patients with excellent improvement had significantly higher serum zinc level than those with no improvement.
Conclusion Our findings suggest that oral zinc supplementation should be considered as a therapeutic option in the treatment of recalcitrant multiple warts. Zinc deficiency is relatively common in our population. Oral zinc supplementation was associated with elevation of serum zinc level, which was associated with clinical improvement in the warts.

Keywords: oral zinc, recalcitrant wart, treatment


How to cite this article:
Moniem EA, Genedy RM, Moussa R. Oral zinc sulfate in the treatment of recalcitrant warts. Egypt J Dermatol Venerol 2016;36:34-8

How to cite this URL:
Moniem EA, Genedy RM, Moussa R. Oral zinc sulfate in the treatment of recalcitrant warts. Egypt J Dermatol Venerol [serial online] 2016 [cited 2018 Sep 18];36:34-8. Available from: http://www.ejdv.eg.net/text.asp?2016/36/2/34/202637




  Introduction Top


Cutaneous warts are benign papillomas of the skin caused by infection with human papillomavirus (HPV). Although cutaneous warts have a benign natural course, patients seek medical advice due to significant physical and psychological impact [1],[2].

The majority of warts regress spontaneously within 1–2 years. Reinfection with the same HPV type is uncommon after clearance, suggesting that protective type-specific immunity may develop. Effective immunity depends on cell-mediated immune response to the early proteins, principally E2 and E6, which promotes the regression of the lesion. Between 10 and 20% of infected individuals do not effectively clear the virus [3],[4].

The most commonly used treatments for warts involve destruction of the area of epidermis infected with the virus. Such treatments may involve application of topical preparations or surgical approaches. The recurrence rates after these therapy modalities may be high. Other therapies aimed at modifying the growth of the epidermis or to stimulate an immune response against HPV are also available [5],[6].

Zinc sulfate is a promising therapy. It acts as an immune modulator. Zinc is a trace element that is essential for the functioning of many enzymes and transcription factors. It is crucial for all highly proliferating cells in the human body, especially the immune system, and innate and acquired immunity can be compromised by zinc deficiency. Treatment of cell cultures with zinc produces polyclonal activation of lymphocytes. Zinc deficiency causes depression at all levels of the immune system. It causes lymphopenia and reduced immune capacity among affected humans [7].

Zinc could counteract viral infections by having an effect on the synthesis of cytokines. In vitro, zinc induces the production of antiviral interferon α (IFN-α) as well as IFN-γ and it can potentiate the antiviral action of IFN-α [8]. In addition, clearance of viral infections requires cytotoxic T lymphocytes, which are highly dependent on zinc [9]. In vivo, not only oral zinc sulfate but also topical zinc oxide has shown therapeutic efficacy in the treatment of viral warts [10].

The aim of this study was to determine the association of low serum zinc levels with persistent viral warts and to assess whether oral zinc sulfate was effective in treating persistent viral warts.


  Patients and methods Top


This randomized case–control clinical trial was conducted on 40 patients selected from the Dermatology Outpatient Clinic of Alexandria Main University Hospital. Patients with five or more warts of at least 6-month duration resistant to one or more lines of treatment were included in the study. Patients who took any immunomodulatory drugs during the previous 6 months were excluded from the study.

Informed consent was obtained from all participants. The Ethics Committee of the Faculty of Medicine, Alexandria University, approved the study.

Blood samples of all patients were taken to determine basic serum zinc level using spectrophotometry. Patients were randomly divided into two groups; each group consisted of 20 patients. Group I received oral zinc supplementation at a dose of 10 mg/kg up to 600 mg maximum daily for 1 month. Group II did not receive any treatment for 1 month. All of the patients were instructed not to take any treatment other than the treatment prescribed in this trial. At the end of the study, the patients were assessed and the serum zinc level was measured. The percent of improvement of the cases was classified as follows: excellent, greater than 75%; moderate, 75–50%; mild, less than 50%; and no change.

Statistical analysis

Data were recorded and statistically analyzed using the IBM SPSS statistics for Windows (version 20.0; IBM Corp., Armonk, New York, USA).

Arithmetic mean±SD were calculated for numerical data. For categorized data, number and percent were calculated. For numerical data, the t-test was used to compare the two groups, whereas for categorized data the χ2-test was used. For more than two groups, analysis of variance test was used. Significance of the obtained results was judged at the 5% level (a P-value of 0.05 was considered statistically significant).


  Results Top


Demographic data of the two studied groups are shown in [Table 1]. There was no significant difference between the two studied groups as regards age, sex, and duration of disease (P>0.05). None of the patients showed clinical signs of zinc deficiency.
Table 1 Comparison between the two studied groups as regards age, sex, and duration of the disease

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Number of warts in group I ranged between 5 and 11 for each patient, with a mean value of 8.25±1.96, whereas in group II it ranged between 5 and 12 for each patient, with a mean value of 8.16±1.76.

At the beginning of the study, serum zinc level in group I ranged between 33 and 152 μg/dl, with a mean value of 85.95±25.61 μg/dl and in group II it ranged between 38 and 162 μg/dl, with a mean value of 81.30±35.87 μg/dl. There was no significant difference between the two studied groups (P=0.254).

After treatment in group I, serum zinc level ranged between 85 and 162 μg/dl, with a mean value of 115.61±19.69 μg/dl. Serum zinc level significantly increased compared with that before treatment in group I (P=0.013). However, in group II, serum zinc level after 1 month ranged between 40 and 165 μg/dl with a mean value of 81.90±36.04 μg/dl without a significant difference compared with that before treatment (P=0.59). Moreover, group I had significantly higher zinc level after treatment compared with group II (P=0.006) ([Table 2]).
Table 2 Comparison between the serum zinc level in group I and group II at the beginning of the study and after 1 month

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The comparison between the two studied groups as regards the percent of improvement after 1 month showed that the percent of improvement in group I was excellent in seven (35%) cases, moderate in six (30%) cases, mild in four (20%) cases, and no change was seen in three (15%) cases. However, in group II, the percent of improvement after 1 month was excellent in 0 (0%) cases, moderate in one (5%) case, mild in three (15%) cases, and no change was seen in 16 (80%) cases. There was a statistically significantly greater improvement in group I than in group II (P<0.05) ([Table 3] and [Figure 1],[Figure 2],[Figure 3]).
Table 3 Comparison between the two studied groups as regards the percent of improvement after 1 month

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Figure 1 (a) Multiple filiform warts in the neck of a male patient. (b) Moderate improvement of lesions after treatment with oral zinc sulfate tablets for 1 month.

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Figure 2 (a) Multiple verrucae vulgaris on the ring and index finger of the hand. (b) Excellent improvement in the lesions after treatment with oral zinc sulfate tablets for 1 month.

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Figure 3 (a) Multiple plantar warts in toes of the foot. (b) Mild improvement of lesions after treatment with oral zinc sulfate tables for 1 month.

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The relation between percent of improvement and duration of disease in group I showed that shorter duration of the disease was associated with better response ([Table 4]).
Table 4 Relation between percent of improvement and duration of disease

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The relation between percent of improvement and serum zinc level after treatment in group I showed that patients with excellent improvement had significantly higher serum zinc level than those with no improvement (P<0.05) ([Table 5]).
Table 5 Relation between percent of improvement and level of serum zinc after treatment in group I

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As regards side effects, only mild epigastric pain was observed in two patients that did not require interruption of treatment.


  Discussion Top


The primary treatment methods of warts are physical destruction such as electrodessication, laser therapy, and cryotherapy. However, these treatments are not suitable for patients with multiple lesions or having fear of pain and scarring. Therefore, immune-modifying agents might be a useful therapeutic alternative because they can be painlessly and easily administrated. In the present study, oral zinc was assumed to be a therapeutic option by modulating the immune system in a patient with viral warts. The results showed greater improvement in the zinc-treated group compared with the control group, which was associated with elevation of the serum zinc level.

Al-Gurairi et al. [11] conducted a more or less similar study. Their placebo-controlled clinical trial was conducted on 80 patients with viral warts. Oral zinc at the same dose was given for 2 months for the first group, and the second group was given a placebo oral treatment in the form of glucose and served as a control group [11].

López-García et al. [12] conducted a double-blind, randomized, placebo-controlled trial on 50 patients with viral warts. Half were randomized to receive oral placebo (starch) and half zinc sulfate at a dose of 10 mg/kg/day for 2 months and both groups were subjected to blood evaluations of zinc, interleukin 2, and IFN-α at baseline and last visit. Response was defined as disappearance of at least 50% of the baseline number of lesions. Their results showed no significant differences in response or clearance rates. In the placebo group, six (24%) patients responded, and in the zinc group seven (28%) patients responded (P=0.94). Four (16%) patients on zinc and three (12%) patients on placebo achieved complete clearance of warts (P=1.00). There was no difference in levels of interleukin 2 and IFN-α among groups, but the final level of zinc was higher in the zinc group (P=0.001). Interestingly, none of the patients in either group had low baseline zinc levels. They suggested that, in patients without zinc deficiency, supplementation with zinc is not superior to placebo in the treatment of viral warts [12]. The difference in results from the present study could be explained by differences in nutrition state of the recruited participants, wherein zinc deficiency was not common as in the present study.

Mun et al. [13] conducted an open-label clinical study on 31 patients with multiple, nongenital viral warts and showed more or less similar results as the present study. The patients were treated with oral zinc sulfate (10 mg⁄kg to a maximum dose of 600 mg⁄day) for 2 months and followed up with assessments for the resolution of their warts and for any evidence of recurrence after treatment. Among the 31 patients, 18 (58%) patients showed low serum zinc levels. Of 26 (84%) patients who completed the study, 13 (50%) showed complete resolution of their warts after 2 months of treatment. Complete responders remained free of lesions at 6-month follow-up. No serious side effects were reported apart from nausea (16%), mild gastric pain (3%), and itching sensation (3%) [13].

In another study by Sadighha [14], the mean level of zinc in those who responded to therapy raised up to 181.5±22.1 μg/100 ml. The mean level of serum zinc after 1 month of treatment in those who did not respond to treatment reached 69±10.11 μg/100 ml. In the remaining six patients, treatment with oral zinc was continued, after which three patients recovered completely, whereas the remaining three patients did not respond to treatment. The mean serum zinc level in patients who responded to treatment increased to 201.3±22.0 μg/100 ml, whereas in the rest of the patients, the mean serum zinc level was 69.8±10.3 mg/100 ml. After a course of 2 months’ treatment with zinc sulfate, the success rate increased to 76.9% (10 patients) [14].

In the study by Yaghoobi et al. [15], 59.3% of the patients responded completely after 1 month of treatment. The mean value of zinc in those who responded increased compared with those who did not respond to treatment. After a 2-month course of treatment with zinc sulfate, the response rate increased to 78.1% (25/32 patients). After 6 months of follow-up in those who received oral zinc therapy and responded to the treatment, no instance of recurrence was noticed. In the control group, 23 patients completed the course of treatment and follow-up. Improvement in warts was seen in three (13%) patients [15].


  Conclusion Top


Our findings suggest that oral zinc supplementation should be considered as a therapeutic option in the treatment of recalcitrant multiple warts. Zinc deficiency is relatively common in our population. Oral zinc supplementation was associated with elevation of serum zinc level, which was associated with clinical improvement in the warts.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bruggink SC, Waagmeester SC, Gussekloo J, Assendelft WJ, Eekhof JA. Current choices in the treatment of cutaneous warts: a survey among Dutch GP. Fam Pract 2010; 27:549–553.  Back to cited text no. 1
    
2.
Van Haalen FM, Bruggink SC, Gussekloo J, Assendelft WJ, Eekhof JA. Warts in primary schoolchildren: prevalence and relation with environmental factors. Br J Dermatol 2009; 161:148–152.  Back to cited text no. 2
    
3.
Stanley M, Pinto LA, Trimble C. Human papillomavirus vaccines-immune responses. Vaccine 2012; 30(Suppl 5): F83–F87.  Back to cited text no. 3
    
4.
Woo YL, van den Hende M, Sterling JC, Coleman N, Crawford RA, Kwappenberg KM et al. A prospective study on the natural course of low-grade squamous intraepithelial lesions and the presence of HPV16 E2-, E6- and E7-specific T-cell responses. Int J Cancer 2010; 126:133–141.  Back to cited text no. 4
    
5.
Sterling JC, Gibbs S, Haque Hussain SS, Mohd Mustapa MF, Handfield-Jones SE. British Association of Dermatologists’ guidelines for the management of cutaneous warts 2014. Br J Dermatol 2014; 171:696–712.  Back to cited text no. 5
    
6.
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. 6
    
7.
Fraker PJ, Jardieu P, Cook J. Zinc deficiency and immune function. Arch Dermatol 1987; 123:1699–1701.  Back to cited text no. 7
    
8.
Berg K, Bolt G, Andersen H, Owen TC. Zinc potentiates the antiviral action of human IFN-alpha tenfold. J Interferon Cytokine Res 2001; 21:471–474.  Back to cited text no. 8
    
9.
Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Arch Immunol Ther Exp (Warsz) 2008; 56:15–30.  Back to cited text no. 9
    
10.
Khattar JA, Musharrafieh UM, Tamim H, Hamadeh GN. Topical zinc oxide vs. salicylic acid-lactic acid combination in the treatment of warts. Int J Dermatol 2007; 46:427–430.  Back to cited text no. 10
    
11.
Al-Gurairi FT, Al-Waiz M, Sharquie KE. Oral zinc sulphate in the treatment of recalcitrant viral warts: randomized placebo-controlled clinical trial. Br J Dermatol 2002; 146:423–431.  Back to cited text no. 11
    
12.
López-García DR, Gómez-Flores M, Arce-Mendoza AY, de la Fuente-García A, Ocampo-Candiani J. Oral zinc sulfate for unresponsive cutaneous viral warts: too good to be true? A double-blind, randomized, placebo-controlled trial. Clin Exp Dermatol 2009; 34:e984–e985.  Back to cited text no. 12
    
13.
Mun JH, Kim SH, Jung DS, Ko HC, Kim BS, Kwon KS, Kim MB. Oral zinc sulfate treatment for viral warts: an open-label study. J Dermatol 2011; 38:541–545.  Back to cited text no. 13
    
14.
Sadighha A. Oral zinc sulphate in recalcitrant multiple viral warts: a pilot study. J Eur Acad Dermatol Venereol 2009; 23:715–716.  Back to cited text no. 14
    
15.
Yaghoobi R, Sadighha A, Baktash D. Evaluation of oral zinc sulfate effect on recalcitrant multiple viral warts: a randomized placebo-controlled clinical trial. J Am Acad Dermatol 2009; 60:706–708.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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