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E-CORRESPONDENCE
Year : 2014  |  Volume : 59  |  Issue : 2  |  Page : 211
Complete clearance of cutaneous warts with hydroxychloroquine: Antiviral action?


Department of Dermatology, Skin Institute and School of Dermatology, N-Block Greater Kailash-1, New Delhi, India

Date of Web Publication21-Feb-2014

Correspondence Address:
Premanshu Bhushan
Department of Dermatology, Skin Institute and School of Dermatology, N-Block Greater Kailash-1, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.127694

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How to cite this article:
Bhushan P, Aggarwal A, Baliyan V. Complete clearance of cutaneous warts with hydroxychloroquine: Antiviral action?. Indian J Dermatol 2014;59:211

How to cite this URL:
Bhushan P, Aggarwal A, Baliyan V. Complete clearance of cutaneous warts with hydroxychloroquine: Antiviral action?. Indian J Dermatol [serial online] 2014 [cited 2019 Nov 17];59:211. Available from: http://www.e-ijd.org/text.asp?2014/59/2/211/127694


Sir,

A 27-year-old female patient with severely symptomatic polymorphic light eruption over bilateral forearms and neck only partially relieved by topical mometasone, sunscreen, and antihistamine was planned to be put on systemic hydroxychloroquine. However, she had numerous histologically confirmed plane warts on her face for past 5 years, and after several previous treatments and recurrences she was not being treated for the past 6 months. In view of the immunomodulatory property of antimalarials, photographs of all wart-affected areas before the initiation of treatment were taken [Figure 1]a-c. Hydroxychloroquine 200 mg twice daily was started after normal routine hematology, serum chemistries, ophthalmologic examination, and glucose 6 phosphate dehydrogenase levels. She was asked not to apply any topical agents on the warts. After 20 days, the light eruption was well controlled and photographs of the warts revealed near-total resolution [Figure 2]a-c. The treatment was continued for another 20 days with complete resolution of light eruption as well as all cutaneous warts. The medicine was then stopped and she was followed up monthly. At 6-month follow-up, no new warts had erupted anywhere on the face or the other parts of body [Figure 3]a-c. This unexpected, extraordinary response made us explore the literature for similar reports.
Figure 1: Cutaneous warts: Baseline photographs

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Figure 2: Near - complete clearance of cutaneous warts after 20 days of hydroxychloroquine therapy

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Figure 3: No recurrence of warts at 6 months after completion of 40 days' course of hydroxychloroquine

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Warts are common skin infections caused by human papillomaviruses (HPVs) of many types. The standard modalities of wart treatment are primarily destructive chemical and physical methods such as chemical cauterization, electrical cauterization, and cryotherapy. These modalities treat only the existing lesions without any effect on the HPV virions in the body, hence recurrences are frequent. Furthermore, these modalities entail a risk of scarring and pigmentary alterations while many patients, especially children, are not cooperative. Most importantly, for numerous warts, those in difficult locations and cosmetically sensitive locations such as face, they are seldom a good choice. In view of these limitations of topical therapy, various systemic agents such as cimetidine, levamisole, and zinc sulfate have been tried in cutaneous warts with variable results of poor evidential value. [1]

Antimalarials are used widely in dermatology for treatment of various disorders such as lupus erythematosus and photodermatoses with limited and well-preventable toxicity profile. [2] Antimalarials are immunomodulatory and could theoretically alter or increase warts by changing host immunity. However, recently, it has been found that antimalarials act as broad-spectrum antivirals by interfering with the endosome-mediated viral entry or the late stages of replication of viruses. [2] Both chloroquine and hydroxychloroquine are weak bases, which accumulate and increase the pH of endosomes, lysosomal, and trans-Golgi network vesicles, disrupting several enzymes, including acid hydrolases, and inhibit the posttranslational modification of newly synthesized proteins. Besides, with these direct actions, they can also act by reducing the inflammatory components of viral infection by reducing proinflammatory cytokines such as tumor necrosis factor-alpha. [2] The antiviral property of chloroquine has been demonstrated for many viruses including human immunodeficiency virus (HIV). [2],[3] The in vitro efficacy of chloroquine/hydroxychloroquine has been confirmed in clinical trials against HIV where in one study chloroquine 250 mg twice daily was found to reduce the viral load significantly. [4]

Spontaneous cure of cutaneous warts is a known phenomenon, but such dramatic response temporally correlated with administration of hydroxychloroquine makes it less likely. The effect observed in our patient may be related to this antiviral property of hydroxychloroquine. An absence of recurrence also is reassuring. In a study to determine rates of HPV infections, abnormal cervical smears, and squamous intraepithelial lesions among women with systemic lupus erythematosus, it was found that patients with normal cervical smears were more likely to be currently receiving hydroxychloroquine compared with those with an abnormal smear. [5] The authors have not associated this finding to antiviral property of hydroxychloroquine, but it would be an attractive explanation. On the contrary, Yu et al., have hypothesized that hydroxychloroquine and other antimalarials, by inhibiting the toll-like receptor-9 (TLR9), may induce persistence of HPV in lupus erythematosus patients. [6] Lupus erythematosus patients, however, per se have increased HPV infection with or without any other treatment. [5],[6] Therefore, the case being presented raises the possibility of clinical antiviral efficacy of hydroxychloroquine against HPV as has been documented against other viruses. [2],[3],[4]

It would be interesting to find the results of using chloroquine/hydroxychloroquine for cutaneous warts in systematic studies in higher number of patients to confirm or refute this observation.

 
   References Top

1.Simonart T, de Maertelaer V. Systemic treatments for cutaneous warts: A systematic review. J Dermatolog Treat 2012;23:72-7.  Back to cited text no. 1
    
2.Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: An old drug against today's diseases? Lancet Infect Dis 2003;3:722-7.  Back to cited text no. 2
    
3.Tsai WP, Nara PL, Kung HF, Oroszlan S. Inhibition of human immunodeficiency virus infectivity by chloroquine. AIDS Res Hum Retroviruses 1990;6:481-9.  Back to cited text no. 3
    
4.Joshi SR, Butala N, Patwardhan MR, Daver NG, Kelkar D. Low cost anti-retroviral options: Chloroquine based ARV regimen combined with hydroxyurea and lamivudine: A new economical triple therapy. J Assoc Physicians India 2004;52:597-8.  Back to cited text no. 4
    
5.Nath R, Mant C, Luxton J, Hughes G, Raju KS, Shepherd P, et al. High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arthritis Rheum 2007;57:619-25.  Back to cited text no. 5
    
6.Yu SL, Chan PK, Wong CK, Szeto CC, Ho SC, So K, et al. Antagonist-mediated down-regulation of toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther 2012;14:R80.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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