The case reported here is similar to experiences in prior informal studies suggesting that topical vitamin A is an effective treatment for verruca vulgaris
. Topical vitamin A should be further investigated as an alternative to the most frequently-utilized wart treatments, cryotherapy and SCA, which have relatively low cure rates [19
]. In contrast to destructive or dermonecrotic treatments, topical vitamin A treatment for warts is not painful and does not lead to scarring. On the other hand, the treatment may require several months for complete resolution of the lesions, which can affect compliance. As in the current case, warts with scar tissue as a result of prior tissue destroying treatments, such as SCA, may require longer vitamin A treatment. The location and size of the wart may also affect time to resolution. Large plantar warts on the feet typically take several months to resolve with topical vitamin A. Treatments such as SCA and cryotherapy have a high rate of recrudescence that is not seen with topical vitamin A treatment. Destructive treatments that do not affect HPV replication must eliminate all virus from the deep tissue, or commonly the wart will reestablish quickly.
There are a number of plausible mechanisms by which retinoids may affect HPV-induced lesions. Warts display abnormal keratin expression [22
]. Retinoids, such as vitamin A, regulate epithelial cell differentiation and keratin expression [25
]. HPV cannot complete its replication cycle in cultured cells suggesting that differentiation of epithelia cells in tissues is important for HPV production [26
]. HPV replication appears to be synchronized with epithelial cell differentiation [27
]. Vitamin A may disrupt the interplay of HPV replication and epithelial cell differentiation, thereby allowing normal tissue to replace the warts. Previous studies have suggested that retinoids may also affect HPV transcription or replication [29
]. Furthermore, HPV infection may alter retinoid signaling [31
]. Immune mechanisms may also be involved in wart clearance [33
]. Vitamin A treatment may increase or prolong expression of HPV T or B cell antigens allowing clearance of the warts by immune mechanisms. The observation that three small warts on the left hand of the current subject resolved simultaneously even though vitamin A was not applied directly to them, suggests the possibility that vitamin A may evoke or potentiate immune responses to warts. While it is unlikely that topical application could increase the systemic levels of vitamin A substantially (hypervitaminosis A), a modest systemic elevation of vitamin A levels by the topical treatment may have affected the small warts on the left hand.
Furthermore, warts can have psychologically devastating effects on patients' lives [34
] and the emotional impact of any treatment should not be overlooked. Treatment with SCA, for example, requires carefully coating the wart with a highly noticeable white film and may not be viable for sufferers who are already self-conscious or whose warts are on their face. In contrast, vitamin A oil is colourless, easy to apply, and quickly absorbed into the tissues. In addition, it does not irritate surrounding skin or lead to drying or flaking. Because vitamin A causes the wart to slowly dissolve and disappear, it represents an inconspicuous treatment that does not attract further attention to the wart and is unlikely to cause additional psychological distress.
Because warts may "spontaneously" resolve, it is possible that clearance of the warts after treatment with vitamin A in this case was due to chance timing. However, this is unlikely given that the warts had only increased in size and number over the preceding 9 years. In addition, the case is typical of subjects in a prior informal series in which warts always began to clear within a few weeks of initiating topical vitamin A treatment [18
]. Tretinoin (Retin A) and other retinoids besides vitamin A have been successfully used in limited studies for the treatment of warts [13
]. The current case adds to the literature suggesting that retinoids should be further investigated in controlled studies to determine their effectiveness in treating common warts and the broad range of other benign and cancerous lesions induced by HPVs.