Cryosurgical Treatment of Warts: Dimethyl Ether and Propane Versus Liquid Nitrogen -- Case Report and Review of the Literature

October 2011 | Volume 10 | Issue 10 | Original Article | 1174 | Copyright © 2011

Abstract

For years, dermatologists have relied on cryotherapy with liquid nitrogen as a safe and effective treatment for warts. More recently, several over-the-counter (OTC) wart-freezing therapies have become available. Manufacturers have substituted liquid nitrogen with dimethyl ether and propane (DMEP), and marketed these new preparations to be safe and effective alternatives to in-office cryotherapy with liquid nitrogen. However, data from in vitro studies and comparative studies in humans refute manufacturers' claims that these products reproduce in-office cryotherapy. J Drugs Dermatol. 2011;10(10):1174-1176.

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INTRODUCTION

Viral warts are benign proliferations of skin and mucosa secondary to infection with human papillomavirus (HPV). To date, over 100 HPV genotypes have been identified. Collectively, these genotypes produce a wide spectrum of disease from the common wart (verruca vulgaris) to the genital wart (condyloma acuminatum).

In 1963, Massing and Epstein published the results of a two-year study which examined the natural history of warts. They found that 70 percent of individual warts studied resolved after two years without treatment. In light of this evidence, one might conclude that no treatment may be appropriate for those individuals who are able to stomach the wart's appearance. In point of fact, however, only 46 percent of these patients remained wart-free after two years.1,2 Thus, the potential for autoinoculation, transmission, and disease recalcitrance demands that these warts be destroyed.

DISCUSSION

Mechanism of Cellular Injury

For years, dermatologists have relied on cryotherapy with liquid nitrogen as a safe and effective treatment for the common wart. The mechanisms by which cryotherapy results in cellular injury is based upon the rapid transfer of heat from the skin to liquid nitrogen, which has a boiling point of -196°C. Rapid cooling of tissue results in direct cellular injury via ice crystal formation and ischemic necrosis secondary to vascular changes. Viral destruction is contingent upon adequate keratinocyte necrosis. The probability of achieving an adequate level of necrosis for effective viral eradication increases with accelerated rates of temperature change during the cooling phase of cryotherapy.

As tissue temperatures fall to -5°C to -15°C, extracellular ice crystals begin to form. The formation of crystals not only mechanically disrupts cellular membranes, but also disturbs fluid homeostasis. During the freezing phase, the extracellular fluid becomes hypertonic. The result is cellular dehydration as water flows from the intracellular to the extracellular space via osmosis. When thawing occurs, the extracellular fluid becomes hypotonic and the rapid flow of water back into the cells may result in rupture of the plasma membrane and cell death. Below -40°C intracellular ice crystals form, further damaging the keratinocyte plasma membrane.3 Vascular changes associated with circulatory failure become evident between the formation of extracellular and intracellular ice crystals, as tissue temperatures fall below -15°C. Microthrombi form within damaged vessels leading to ischemic necrosis.4 Thus, the degree of keratinocyte necrosis is dependent upon both the rate of cooling and the minimum tissue temperature achieved.

An End to In-office Cryotherapy for Warts?

In recent years, several OTC wart-freezing therapies have become available. These products substitute liquid nitrogen with DMEP. Manufacturers market these preparations to be safe and

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