Sanguinaria extract, a mixture of benzophenanthridine alkaloids derived from the common bloodroot plant ( Sanguinaria canadensis ), has been used in oral rinses and toothpaste products since 1982. The most widely used product with Sanguinaria, Viadent, has been shown, through extensive clinical trials, to be effective against plaque buildup and gingivitis.Importantly, sanguinaria extract has also been shown to be carcinogenic in many studies.In 1999, Damm and associatesreported an increased prevalence of leukoplakia of the maxillary vestibule in patients who used sanguinaria-based products on a routine basis.
They conducted a retrospective review of 88 patients with leukoplakia of the maxillary vestibule and found that 84.1% of the patients reported having used Viadent. The prevalence of Viadent use was only 3% among randomly selected adults in their study. Eversole and colleaguescompared and contrasted biomarkers and ploidy data from maxillary gingival leukoplakias associated with dentifrices and mouth rinses containing sanguinaria with those from other forms of benign and premalignant mucosal keratosis. They used computerized image analysis and biomarker immunohistochemical assays to assess ploidy, DNA content, and p53 and proliferating cell nuclear antigen immunoreactivity of nuclei in tissue from these groups. A significantly higher (fourfold) DNA content and higher numbers of cells with hyperploid nuclei were found in the group with sanguinaria-associated keratoses. Although this group did not harbor significant numbers of p53-expressing nuclei, a significant elevation in nuclei labeled with proliferating cell nuclear antigen was noted. The authors concluded that sanguinaria-associated keratoses show marker and image analysis profiles similar to those of non-sanguinaria-induced dysplastic lesions of the lip and mucosa.Hence, preparations containing sanguinaria should be avoided until the risk for malignant transformation is determined.This recommendation is further supported by the lack of regression in some Viadent-induced leukoplakias months after the cessation of Viadent use.TYPICAL FEATURES
Most patients are adults in the fourth to ninth decades of life. In the study by Damm and colleagues, the range of Viadent use before the development of lesions was 6 months to 12 years, with a mean of 4.4 years.Typically, patients present with a white, velvety, wrinkled or corrugated patch of leukoplakia in the maxillary vestibule, involving both the attached gingiva and vestibular mucosa (Figure 5-13, A). The lesions may also be seen in the anterior mandibular vestibule (see Figure 5-13, B). The area is usually very distinct and sharply demarcated from the surrounding tissue. The lesions are localized to these areas since the anterior portions of the maxillary and mandibular
vestibule exhibit prolonged retention of the product due to the greater distance from the major salivary ducts. Histopathologically, all biopsy specimens demonstrate significant surface keratosis with a verrucoid pattern. Minimal atypical changes (including basilar hyperplasia, nuclear hyperchromatism, and increased nucleocytoplasmic ratios) limited to the lower one-third of the epithelium are noted in most specimens. More significant atypical changes have also been reported.
TREATMENT
No appropriate treatment has been established for sanguinariainduced leukoplakia. However, an initial biopsy is mandatory. If a histopathologic diagnosis of dysplasia is rendered, the condition should be treated in a fashion similar to the treatment of other potentially premalignant processes. The less severe changes should be managed according to clinical judgment, depending on the extent and duration of the lesion. In all cases, complete discontinuation of Sanguinaria-containing products and cessation of any other harmful habits such as tobacco or alcohol use is mandatory. All patients should be given careful clinical followup, with a biopsy of any recurrent or worsening lesion(s).
TREATMENT
No appropriate treatment has been established for sanguinariainduced leukoplakia. However, an initial biopsy is mandatory. If a histopathologic diagnosis of dysplasia is rendered, the condition should be treated in a fashion similar to the treatment of other potentially premalignant processes. The less severe changes should be managed according to clinical judgment, depending on the extent and duration of the lesion. In all cases, complete discontinuation of Sanguinaria-containing products and cessation of any other harmful habits such as tobacco or alcohol use is mandatory. All patients should be given careful clinical followup, with a biopsy of any recurrent or worsening lesion(s).