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Date Posted: 18:20:01 07/24/02 Wed
Author: moonotter
Subject: Outbreaks of Oral Warts Coinciding With HAART?

Outbreaks of Oral Warts Coinciding With HAART?


Medscape HIV/AIDS 8(2), 2002. © 2002 Medscape
Posted 07/10/2002


Question
A very difficult-to-manage patient with advanced AIDS, HIV cholangiopathy, and hepatitis C was finally started on a triple-drug regimen which his liver could tolerate. Since then he has had multiple, severe outbreaks of oral/lingual/buccal warts which disappear when he is off medications but reappear when his therapy is restarted. We are unable to control them with local measures. Any suggestions on management?


Response
from Graeme Moyle, MD, MBBS , 07/11/2002

A striking increase in oral warts has been reported in surveys comparing the HAART vs pre-HAART eras. For example, in one report oral warts were 3-fold more common in patients on antiretroviral therapy and 6-fold more common among those on HAART (P = .01).[1] In another study, oral warts were associated with reductions in viral load,[2] which suggests that this phenomenon may in part be related to immune reconstitution, as described in this case.
The warts may spontaneously resolve with further immune recovery but this may take many months or longer. The mainstays of wart treatment are local destructive therapy and immunomodulation.

The principle of locally destructive therapy is to avoid leaving more damage behind than is being caused by the wart. The oral mucosa recovers readily from freezing with directed liquid nitrogen sprays. This may be suitable for debulking and treating lesions on the gums and tongue in accessible areas. YAG lasers (as used for warts in the anal canal) and direct surgical excision may also be used by an experienced surgeon. Intralesional treatment may also be helpful. Bleomycin has been used for oral warts in an HIV-infected person,[3] and in another report a small series of patients with oral warts were treated with intralesional interferon-alfa.[4]

Immunomodulators are generally more gentle therapy, but there is less reliable evidence of their efficacy. Multiple randomized trials have generally failed to prove benefits. In an Iraqi study, zinc sulfate at a range of doses was reported to be superior to placebo for recalcitrant skin warts in immunocompetent patients with low plasma zinc levels,[5] although high-dose zinc should be used with caution in HIV-infected patients and plasma levels are unreliable. Methisoprinol (isoprinosine or inosine pranobex), a synthetic agent with immunomodulatory properties and some antiviral activity against HPV, was reported to reduce recurrence of proliferative verrucous leukoplakia, an oral lesion linked to HPV, in a nonrandomized comparative series.[6] Oral isotretinoin (1 mg/kg daily) for 3 months was associated with around 50% complete or partial response rates in a series of persons with recalcitrant skin warts[7] but has not been tested in randomized studies. Finally, there are anecdotes about the use of cimetidine for warts but randomized trials did not reliably indicate benefit,[8] causing one dermatologist to dub it a modern day "snake oil."[9] Its use with levamisole is superior to cimetidine alone for recalcitrant warts in children.[10]

In the long term, successful management of oral warts will rely on effective HIV therapy. Short-term therapy may be a matter of trial and error.



References
Greenspan D, Canchola AJ, MacPhail LA, Cheikh B, Greenspan JS. Effect of highly active antiretroviral therapy on frequency of oral warts. Lancet. 2001;357:1411-1412.
King MD, Reznik DA, O'Daniels CM, Larsen NM, Osterholt D, Blumberg HM. Human papillomavirus-associated oral warts among human immunodeficiency virus-seropositive patients in the era of highly active antiretroviral therapy: an emerging infection. Clin Infect Dis. 2002;34:641-648.
Girao L, Franca I, Macedo H, et al. Treatment of oral condylomata acuminata in a HIV-1 patient with bleomycin. J Eur Acad Dermatol Venereol. 2000;14:321-322.
Lozada-Nur F, Glick M, Schubert M, Silverberg I. Use of intralesional interferon-alpha for the treatment of recalcitrant oral warts in patients with AIDS: a report of 4 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:617-622.
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.
Femiano F, Gombos F, Scully C. Oral proliferative verrucous leukoplakia (PVL); open trial of surgery compared with combined therapy using surgery and methisoprinol in papillomavirus-related PVL. Int J Oral Maxillofac Surg. 2001;30:318-322.
Tsambaos D, Georgiou S, Monastirli A, Sakkis T, Sagriotis A, Goerz G. Treatment of condylomata acuminata with oral isotretinoin. J Urol. 1997;158:1810-1812.
Rogers CJ, Gibney MD, Siegfried EC, Harrison BR, Glaser DA. Cimetidine therapy for recalcitrant warts in adults: is it any better than placebo? J Am Acad Dermatol. 1999;41:123-127.
Bigby M. Snake oil for the 21st century. Arch Dermatol. 1998;134:1512-1514.
Parsad D, Pandhi R, Juneja A, Negi KS. Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in children. Pediatr Dermatol. 2001;18:349-352.




Graeme Moyle, Associate Director of HIV Research, Department of HIV, Chelsea & Westminster Hospital, London
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