Universal Journal of Medical Science 2(3): 25-30, 2014 http://www.hrpub.org DOI: 10.13189/ujmsj.2014.020301 Relevance of Herpes Simplex Virus Infection to Oral Lichen Planus Sang-Yeon Park, Eung Ho Choi* Department of Dermatology, Yonsei University Wonju College of Medicine *Corresponding Author : [email protected] Copyright © 2014 Horizon Research Publishing All rights reserved. Abstract Background: Oral lichen planus (OLP) is a and occurs twice as often in females2. While lichen planus chronic inflammatory disease involving the oral mucosa that of hairless skin is generally cured spontaneously, OLP is induces pain and burning sensations, thus decreasing a chronic, has a tendency to recur, is mostly not cured patient’s quality of life. Although its etiology has not yet spontaneously, and has a possibility of malignant been clearly defined, infection has been suggested to be transformation3. Various clinical symptoms can arise with associated with OLP. We tried to clarify the relevance of OLP: Pain is the most common, and a burning sensation, herpes simplex virus (HSV) infection in OLP, since HSV itching, and irritation may also occur. OLP also precludes infection is the most common infection in the oral mucosa of patients from consuming hot or spicy food, therefore, adults with characteristics of recurrence due to psychological further degrading their quality of life4-6. and physical stress. Methods: We enrolled thirty subjects The precise cause of OLP has not yet been elucidated, but diagnosed with OLP by clinical manifestation and an immune reaction of cytotoxic T cells in keratinocytes is pathologic findings. We tested serum IgG levels against thought to be a main cause7-9. There are various factors that HSV-1 and 2, and performed PCR testing of biopsy affect such an immune reaction, including allergens, drugs, specimens for HSV. Additionally, we assessed the treatment and viruses10, 11. Other hypotheses regarding its pathogenesis effect of an oral anti-viral agent for OLP. Results: Serum include consistent irritation due to dentures or amalgams, HSV-1, 2 IgG levels were markedly elevated in the OLP drug response, infection, an autoimmune condition, and subjects. HSV DNA was not found in the PCR biopsy genetic polymorphism12-15. One prominent hypothesis states specimens. Eight out of thirteen subjects(61.5%) who took that oral infection is involved in initiating OLP. Herpes oral acyclovir improved in subjective symptoms and simplex virus (HSV) infection is the most common objective lesion manifestations. OLP patients treated with infectious disease in the oral mucosa of adults, and conventional treatments showed improvement in 58.8%. frequently recurs due to psychological or physical stress. We Conclusions: Although we did not observe decisive findings, performed this research to find out whether HSV infection is such as a positive HSV-PCR result, to establish a link relevant to the occurrence of OLP, and if antiviral treatment between HSV and OLP, we did observe an increase in HSV could be used as an alternative treatment option for OLP. IgG levels and a therapeutic response to oral acyclovir in subjects with OLP. Keywords Oral Lichen Planus, Herpes Simplex Virus, 2. Methods Acyclovir 2.1. Subjects This study was conducted with 30 adult OLP patients over 1 . Background 30 years of age who visited the Department of Dermatology, Wonju Severance Christian Hospital over a seven-year Lichen planus, first reported by Erasmus Wilson in 1869, period (2005 to 2011). The subjects were diagnosed with is a mucocutaneous disease that involves skin, oral, and OLP through characteristic clinical features and genital mucosa, hair follicles of the scalp, and finger nails1. histopathological findings. Serum IgG antibodies to HSV-1 Among these, oral lichen planus (OLP) is a chronic and HSV-2 were tested. And the subjects who did not show inflammatory disease of unknown cause that occurs in the response to conventional treatment such as topical steroid, oral mucous. It is a relatively common disease in oral intralesional steroid injection, topical calcineurin inhibitor mucosa that appears in approximately 1-2% of the were treated with oral acyclovir. Control group were treated population. OLP affects mostly adults in their 40s and 50s, with conventional treatments (Fig. 1). 26 Relevance of Herpes Simplex Virus Infection to Oral Lichen Planus Figure 1. The clinical manifestations and histopathological findings of patient Reticulated white streaks (Wickham striae) on reddish patches were observed in gingival mucosa of patient 3(a), and in buccal mucosa of patient 10(b). Histopathological findings showed acanthosis with saw-tooth rete ridges, basal degeneration, and band-like infiltration of lymphocytes in the upper dermis in patient 3 (c: H&E x40, d: H&E x 100). 2.2. History Taking and Physical Examinations 2.4. Evaluation of response to treatment We obtained information on the subjects’ subjective and Oral acyclovir was prescribed to the OLP subjects (400mg objective symptoms, disease duration, medical history, and daily) who did not show improvement by conventional treatment history by reviewing medical records, and added treatments. All patients were periodically assessed the the clinical manifestations of OLP using photographs. improvements to the OLP lesions and subjective symptoms. 2.3. Histopathology and HSV-PCR Study 3. Results Biopsies were done on the OLP subjects’ lesions. Based on characteristic clinical manifestations and typical 3.1. Epidemiological and Clinical Characteristics of histopathology, we confirmed OLP in the subjects. Using the Subjects biopsied specimens, polymerase chain reaction (PCR) testing was done to detect HSV DNA. The DNA of Among the OLP subjects, thirteen were female and HSV-infected cells was used as a positive control. The DNA seventeen were male, and their average age was 57.6 years. of normal tonsil tissue or distilled water was used as a The disease duration of OLP varied from several weeks to 10 5' 3' negative control. GCG CTT GTC ATT ACC ACC GC years, with 19.4 months on average. Among the 30 patients, 5' 3' and TAC CCG AGC CGA TGA CTT AC were used as thirteen had developed OLP in their 50s and six in their 60s, primers. We encased the extracted template DNA in a composing more than half the subjects. Most common microcentrifuge tube and added 1X PCR buffer. These clinical type was reticular type(61.5% in antiviral treated samples were denatured in a thermal cycler at 94 for 5 group, 58.8% in control group) and followed by erosive and minutes. We read the 118 base pair PCR band to confirm atrophic type. In antiviral treated group, erosive and atrophic HSV DNA. ℃ type was 23.1% and 15.4% respectively. In control group, they were 29.4% and 5.9% (Table 1). All the subjects complained of pain and burning sensations in the oral mucosa and could not eat either spicy or hot food. Universal Journal of Medical Science 2(3): 25-30, 2014 27 Table 1. Clinical types and previous treatment of enrolled patients with oral lichen planus Antiviral treatment Conventional treatment group(n=13) group(n=17) Age(mean±S.D : years) 55.4±12.0 59.3±12.8 Sex Male 5 (38.5%) 12 (70.6%) Female 8 (61.5%) 5 (29.4%) Duration(mean±S.D : months) 21.2±27.5 17.6±22.9 Clinical types Reticular 8 (61.5%) 10 (58.8%) Atrophic 2 (15.4%) 2 (11.8%) Erosive 3 (23.1%) 5 (29.4%) Previous treatments Topical steroid 10 5 Intralesional steroid injection 4 9 Topical calcineurin inhibitor 1 4 Cryotherapy 0 8 3.2. Serologic HSV IgG Antibody Test and HSV-PCR calcineurin inhibitor. We regarded as no response if there Using Biopsy Tissues was no improvement to more than 3 months of conventional treatments. The patients who did not respond to these We examined the HSV-1 and HSV-2 IgG titers in therapies were treated with antiviral agent. The intralesional seventeen patients, the average of HSV-1 and HSV-2 IgG steroid injection was most commonly used treatment remedy, titer was 4209.15 and 1071.61, respectively. These were followed by cryotherapy, treatment with topical steroids. In 10.5-fold higher and 3.5-fold higher than normal range. In thirteen subjects, daily acyclovir (400 mg) was prescribed, the PCR on HSV DNA performed with tissue specimens they took acyclovir for about 4.3months. In 61.5% of taken from the 11 OLP subjects, HSV DNA was not found in patients who underwent antiviral treatment, the symptoms all subjects. and lesions were improved and about 23.1% showed marked improvement. In patients who treated with only conventional 3.3. Response of OLP to Treatments therapies, the symptoms were improved in 58.8% and 5.9% of patients showed marked improved (Fig. 2) (Table 2). All patients underwent with conventional treatment such as topical steroid, intralesional steroid injection, topical Table 2. Response of OLP patients to treatment Antiviral treatment Conventional treatment group (n=13) group (n=17) No 5 (38.5%) 7 (41.2%) Mild 5 (38.5%) 3 (17.6%) Moderate - 3 (17.6%) Much 3 (23.1%) 1 (5.9%) * No: no response, Mild: improvement < 30% Moderate: 30% < improvement < 60%, Much: 60% < improvement 28 Relevance of Herpes Simplex Virus Infection to Oral Lichen Planus Figure 2. The OLP lesion after the treatment with oral acyclovir After five months of treatment with oral acyclovir (400mg daily), the OLP lesion on the lower lip was much improved in patient 11 (a: before the treatment, b: after the treatment). 4. Discussion reported that the mucosal LP is associated with autoimmune diseases, such as thyroid disease, Sjogren syndrome, HSV infection is one of the most common oral infectious multiple sclerosis. A study reported that about 28% of diseases and recurs depending on a patient’s level of stress mucosal LP patients had at least one more autoimmune and body condition.