A 25-year-old man appeared to have a new form of a well-described disorder. In March 2011, he presented to our clinic complaining of a 6-month history of tongue ulcerations that made it difficult for him to talk and eat. After evaluation at a local hospital, he received an initial diagnosis of chronic ulcerative stomatitis.
However, the lesions were unresponsive to multiple medications, so he was seeking a second opinion. Specifically, a combination of tripterygium hypoglaucum, a Chinese medicinal herb, 2 g three times a day for 20 days; prednisone acetate, 20 mg once a day for 8 days; a local injection of triamcinolone acetonide, 8 mg once a week for 3 weeks; and regular topical use of chlorhexidine gargle was unsuccessful. He was otherwise healthy and denied a history of oral trauma, insect bites, allergies, or systemic diseases.
Assessment
A physical examination revealed a 3 × 1 cm elevated and flexible overgrowth on the left ventral lingual surface. The lesion had a pale yellow pseudomembrane and shallow erosions. White reticular striae formed a lacy network at the border of the plaque. A similar second lesion, measuring 2 × 1 cm, was noted on the right ventrum of the tongue (Figure 1). No local source of stimuli, such as amalgam, friction from sharp cusps, or rough dental restorations, was observed, and no skin lesions were noted.
A full blood count was ordered, along with T-cell counts (CD3+, CD4+, CD8+) and quantitative immunoglobulin tests for IgA, IgE, IgG, and IgM. In addition, the patient’s blood glucose level was measured, as were electrolyte levels and markers for liver and kidney function. All results were normal. Testing for human immunodeficiency virus and syphilis proved negative. Findings from assays for antinuclear antibodies, anti-double-stranded DNA antibodies, anti-ribonucleoprotein antibodies, anti-Sjögren’s syndrome (SSA, SSB) antibodies, anti-scleroderma (Scl-70) antibodies, anti-Jo-1 antibodies, anti-ribosomal P protein antibodies, C3 and C4 complement components, circulating immune complexes, and rheumatoid factor were unremarkable.
Epithelial hyperparakeratosis and a marked layer of lymphocyte infiltrate immediately underlying the epithelium were noted on a biopsy sample from the lesion on the ventral tongue mucosa (Figure 2). Vacuolization was observed in parts of the epithelial and basal cells (Figure 3). Typically, in autoimmune bullous diseases, immunoreactants such as IgA, IgG, IgM, or complement C3 are deposited along the basement membrane or in the intercellular regions of the epithelium. But deposition of these proteins was undetectable when the lesion was examined by direct immunofluorescence.
Diagnosis
Although vacuolization has not been previously described, the other findings from the physical and pathologic examinations were most consistent with a diagnosis of oral lichen planus. Human papillomavirus is often associated with oral exophytic lesions, but a test for human papillomavirus 16/18 was negative.1 Further testing for other human papillomavirus genotypes or viral types was declined by the patient, as he wished to return home. Therefore, the pathogenic factor remained unknown.
Oral lichen planus is a chronic, inflammatory, autoimmune disorder of unknown etiology. Several inciting factors have been proposed, including genetic background, dental materials, drugs, bacterial or viral infections, other autoimmune diseases, diabetes, hypertension, and stress.(2) Six clinical variants have been described: reticular, papular, plaque-like, atrophic or erythematous, and the erosive forms, which are ulcerative and bullous. These types often coexist in various combinations.
Management
After the diagnosis was made, we prescribed prednisone acetate, 25 mg, once a day for 10 days and compound borax solution to be used as mouthwash. Prednisone is a well-accepted treatment option for the erosive form of oral lichen planus, but this patient had no improvement in the lesion. Given that the exophytic lesions might be associated with human papillomavirus infection, we then treated him with pidotimod, an oral immunostimulant (produced in China and Italy but not available in the United States), 0.4 g twice a day for 1 month, followed by intramuscular injection of bacillus Calmette-Guerin polysaccharide nucleic acid (BCG-PSN), 1 mL, every other day for another month to improve immune function. The lesion and his symptoms improved remarkably; the elevated growths gradually became flat and had almost disappeared after 2 months (Figure 4). He was last seen for follow-up in March 2013. At that time, his lesion remained stable. Although white reticular striae were still present, we saw no relapse or new growths.
Interestingly, 2 months later, a 14-year-old boy presented with similar symptoms. He had a 2 × 1 cm elevated overgrowth on the right ventrum of his tongue and multiple white reticular lesions on the buccal mucosa, bilaterally, and on the ventral lingual surface. Taking advantage of our previous experience, we treated him with a 42-day course of oral pidotimod, 0.4 g daily. The prominence disappeared, as expected, leaving only white striae.
Several features made us consider this as a novel clinical variant of oral lichen planus. First, the lesion showed typical histological features of oral lichen planus but had an atypical clinical appearance. To our knowledge, the hyperplastic lesions with white striae have not been previously described in the literature.3 Second, the vacuolization of epithelium, as observed by light microscopy, has not been described in oral lichen planus. However, vacuolization is associated with viral infections and may have contributed to the rare clinical presentation.4 We hypothesize that the background of friable reticular lesions made the epithelium more susceptible to a break, facilitating inoculation by some kind of virus. Then an immunological reaction resulted in lesion formation. Third, corticosteroids are the most widely used agent in the treatment of oral lichen planus because of their ability to suppress cell-mediated immune activity.5 Yet our first patient showed poor response to classical immunosuppressive agents and instead responded well to treatment with immunostimulants and immunomodulators.
We present 2 cases of a rare clinical variant of oral lichen planus—a hyperplastic form that might be related to an overlying viral infection. Both were successfully cured. Physicians who encounter a similar lesion, especially in young patients, should be aware that oral lichen planus is a possible diagnosis. Additionally, pidotimod or BCG-PSN served as effective treatments after a timely diagnosis.
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– Xin Jin, DDS, PhD, Ting Hu, DDS, PhD, Xuefeng Zhao, DDS, PhD, Qianming Chen, DDS, PhD, Xin Zeng, DDS, PhD
This article originally appeared in the January 2014 issue of The American Journal of Medicine.
