Burning Mouth: an Initial Examination of a Potential Role of Herpes Virus Infection

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Oral Med Pathol 11 (2006) 45

Burning Mouth: An Initial Examination of a Potential Role of Herpes Virus Infection

Joel B. Epstein1, Miriam Grushka2, Christopher Sherlock3, Matthew S. Epstein4 and Meir Gorsky5 1Department of Dentistry, Vancouver Hospital and Health Sciences Center,Vancouver British Columbia, Canada; currently Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois, Chicago, Illinois, USA 2Department of Dentistry,Vancouver Hospital and Health Sciences Center, Vancouver British Columbia, Canada; currently Private Practice, Toronto, Ontario, Canada 3Department of Pathology & Laboratory Medicine, University of British Columbia/St. Paul’s Hospital, Department of Virology, University of British Columbia, Vancouver British Columbia, Canada 4Department of Dentistry, Vancouver Hospital and Health Sciences Center, Vancouver British Columbia, Canada; currently School of Dentistry, University of Washington, Seattle, Washington, USA 5Department of Dentistry, Vancouver Hospital and Hearth Science Center, Vncouver British Columbia, Canada; currentry, Department of Oral Pathology and Oral Medicine, School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel

Epstein JB, Grushka M, Sherlock C, Epstein MS and Gorsky M. Burning mouth: an initial examination of a potential role of herpes virus infection. Oral Med Pathol 2006; 11: 45-48, ISSN 1342-0984

Burning Mouth Syndrome (BMS) is a burning sensation of the oral mucosa that occurs in the absence of a clinical or laboratory finding. Since herpes virus infections are common in the oropharynx, a possible association between BMS and post-herpetic neuralgia was speculated. The purpose of the present study was to evaluate a potential viral role in the etiology of BMS. Materials and Methods: Viral serology (HSV, CMV, VZV IgM and IgG) obtained from 9 patients with BMS was compared to that of 13 patients with other oral mucosal conditions. Results and Discussion: The general profile of the BMS patients in this trial fits the profile of these patients reported in the literature. No IgM seropositivity for any of the 3 viruses was recorded in the BMS patients. Although most subjects in the two groups were positive for HSV, CMV, and HZV IgG, no difference in the prevalence was noted between burning mouth and the control groups. The positive IgG findings indicate past exposure to the viruses as expected in the general population. Although no evidence was found that would support the presence of an active viral infection in BMS subjects, the possibility of a “hit and run” role for viral damage in BMS could not be ruled out based on the present sample.

Key words: herpes simplex virus, varicella-zoster virus, cytomegalovirus, burning mouth syndrome, oral neuropathic pain Correspondence: Joel B. Epstein, Department of Oral Medicine and Diagnestic Sciences, College of Dentistry, 801 S. Paulina St, Chicago, Illinois, USA Phone: +312-996-7480, Fax: +312-355-2688, E-mail: [email protected]

Introduction The pain is usually described as burning with as- Burning Mouth Syndrome (BMS) is defined as a sociated dysesthetic qualities similar to those present in burning sensation in the tongue and/or other oral mu- other neuropathic pain conditions. Although psychologi- cous membranes not associated with any identified clinical factors are often prominent in BMS, no clear evidence cal signs and laboratory findings (1, 2). There is no clear of a close causal relationship between psychogenic fac- understanding of its etiology or pathogenesis (3, 4) and tors and burning mouth has been reported (7). The pain diagnosis remains essentially clinical by exclusion of other often begins spontaneously (2) and increases in intensity diseases. BMS is considered a chronic disorder and in over a short period of time before it plateaus. Approxi- the few studies that have looked at spontaneous remis- mately one third of the subjects attribute the onset of sion in BMS, at least a partial remission may occur within their oral burning to a dental procedure or illness, such 6 to 7 years after onset in up to two-thirds of subjects (5, as an upper respiratory infection (2). 6). In view of the relatively rapid onset, as well as the 46 Epstein et al. Herpes viruses and burning mouth syndrome relatively high prevalence of BMS in more than 1.0% in the BMS patients, a subjective sensation of oral dryness the general population [higher in post-menopausal women was reported by 75%, and taste changes were reported (7)] and the quality of pain, the possibility that BMS fol- by 22% of the subjects. The onset of the burning sensa- lows a viral infection can be considered. Herpes virus tion of BMS was described as gradual by 71.4% of the infections are common in the oropharynx and it is pos- patients and as sudden by 28.6%. The 13 subjects who sible that neuropathic effects may follow oropharyngeal had identifiable oral lesions associated with their oral infection associated with nerve infection (8). Since the burning served as control subjects, of these 11 had evi- possible association between BMS and Herpes virus as- dence of erosive lichen planus and two suffered from post- sociated nerve damage as in post-herpetic neuralgia fol- radiation therapy mucosal sensitivity. None of this group lowing Herpes zoster infections, has not been investigated, reported taste alterations and 6 patients (46.1%) reported the purpose of this preliminary study was to evaluate the oral dryness. No patients in either group demonstrated potential viral role of Herpes viruses in patients with decreased salivary flows on salivary collection. burning mouth symptoms. The severity of the discomfort on a visual analog scale ranging from 0 to 10 with the following anchors “no Material and methods discomfort” to “extremely painful” was assessed. In the Patients with complaints of oral burning were en- BMS subjects VAS pain was a mean of 6.3. In addition rolled following completion of institutional informed con- to burning of the lips and the cheeks, tongue involvement sent. A standard history was acquired and oral examina- was reported by 5 patients (55.6%) with BMS. Taste tion completed. BMS was diagnosed when there was an changes were reported by 2 male subjects (22.2%). absence of oral changes, and standard screening blood Table 2 shows medication use of the 22 individuals tests for blood glucose, anemia, iron deficiency, folate, B12 with oral pain. Pain control medications were used mostly were negative (9). Consecutive patients with oral burn- by individuals in the control group and only 23% of this ing had viral serology completed (HSV, CMV, VZV, IgM group of patients used antidepressant medications; how- and IgG), using the appropriate ELISA tests (Dade ever, a majority of the BMS patients (78%) used antide- Behring Inc; Newark DE). Whole resting salivary flow pressants. was assessed by having patients collect saliva for 5 min- The results of the serologic tests for HSV, CMV and utes while at rest and while stimulated by chewing VZV are shown in Table 3. All but one subject in both the unflavored chewing gum base for 5 minutes, after which study and control groups were negative for IgM antibody the collections were weighed (4). Controls were consecu- to the Herpes viruses tested. However, one patient of the tive patients with identified oral mucosal conditions in control group, a 64 year old woman with oral and left whom oral discomfort was present. facial pain compatible with the diagnosis of Herpes zoster, was found to be positive for VZV IgM antibody. Most sub- Results jects in the two groups were positive for HSV, CMV and The characteristics of the 22 subjects in the study HZV IgG and no difference was found in the prevalence group are presented in Table 1. The mean ages of the male of the positive findings between the two groups. and female study subjects was not significantly different. Tobacco use was low: 14.2% of men and 7.1% of women Discussion smoked. Approximately 62% of the study group reported Although there is strong evidence from clinical some alcohol consumption, which was limited to beer or studies to suggest that people who present with BMS are wine and was for most individuals only on social occa- mostly post-menopausal women (2, 7), some recent epi- sions; however, for one man and three women (23% of demiological data suggests a more equal male to female study subjects) daily alcohol consumption was reported. ratio (10, 11). We identified an approximately equal male Mouthwashes were used by 10 subjects (47.6%); almost to female ratio in our small series of consecutive clinical half of these subjects reported using rinses more than cases. The distribution of oral sites most often involved once daily. were the anterior tongue, anterior hard palate and the Even though all patients complained of discomfort lower lip (2), consistent with the subjects identified in and pain in the oral cavity, exclusion of any clinically iden- this study as experiencing BMS. tified etiology resulted in 9 patients with a clinical diag- The general profile of the BMS patients in the nosis of BMS. The mean age of the patients diagnosed present study fits the profile of BMS as reported in the with BMS was 56.6 years (57.6 years for women and 55.5 literature (12). We identified an almost equal sex distri- years for men). Of the nine BMS patients, 4 were males bution in our clinic cases, comparable to the epidemiol- and 5 females, who suffered oral burning for a mean of ogy studies of BMS, but in contrast to most clinical trials 30.8 months (36.5 months for men and 26.4 months for which reported a preponderance of female patients. The women). Only 1 of these patients (11.1%) was a prior mean age of our BMS patients was 57 years and the com- smoker and 44.4% used alcohol on social occasions. In plaint of oral dryness was common (75%) despite normal Oral Med Pathol 11 (2006) 47

Table 1: Characteristics of the study group Age in years Gender / No. mean (range) Tobacco users (%) Alcohol users (%)

Male 7 55.14 (48-61) 14.2% 57.1%

Female 15 55.20 (43-68) 7.1% 64.2%

Total 22 55.28 (43-68) 9.5% 61.9%

Table 2: Consumption of medications in 22 individuals with oral pain

BMS CONTROL

No A.Dep. Neuro Pain No A.Dep Neuro Pain

Male 4 3 3 1 3 0 1 1

Female 5 4 1 1 10 3 1 4

Total 9 7 4 2 13 3 2 5

A. Dep. = antidepressants Neuro. = antineuralgia

Table 3: Positive IgG findings in serologic tests of the BMS and control groups (%)

HSV CMV HZV

No. IgM IgG IgM IgG IgM IgG

BMS 9 0% 66.7% 0% 66.7% 0% 100%

Control 13 0% 66.7% 0% 66.7% 11.1%* 88.9%

* One control patient diagnosed with herpes zoster infection.

salivary production in accord with other studies (4). Al- patients. In this study, we also noted patient reports of though, the subjects’ use of tobacco and alcohol were pro- dry mouth in 75% of the BMS patients consistent with vided as descriptive data, this study was not able to as- previous studies (9). sess any role of tobacco or alcohol use in BMS, and this is Management of the patients with BMS using cen- not suggested in the literature. trally-acting medications resulted in control of symptoms A number of clinical studies (2, 4, 7) suggest that in approximately 2/3 of patients, using tricyclics or in BMS, the burning may be accompanied by dry mouth, benzodiazpam (clonazepam), comparable to previous stud- thirst, and dysguesic taste. For example, in an age- and ies (7, 13). sex-matched control study, Grushka (2) found approxi- Both study and control groups were positive for mately 70% of BMS subjects, compared to 11% of con- Herpes virus specific IgG and there was no difference in trols subjects, reported either changes in their ability to prevalence, indicating past exposure to the viruses in both taste or a persistent dysgeusic taste, especially bitter and/ the BMS and control subjects, comparable to that of a or metallic. These findings were confirmed in later stud- general adult population (about 70%) (14). In the present ies at the Connecticut Chemosensory Research Clinic (4). study we found no evidence of an association between Another epidemiological study (11) also reported that 40% BMS evidence of active HSV, CMV, VZV infection (based of patients with burning complaints reported an alter- upon virus specific IgM) and or past infection (based upon ation in taste. Although only 22% of the BMS patients in virus specific IgG), suggesting no relationship between the present study reported altered taste, our findings these viral infections and BMS in this group of subjects. support an association between taste and BMS in some If BMS does represent a chronic post-infectious 48 Epstein et al. Herpes viruses and burning mouth syndrome condition related to the herpes viruses in a subset of cases, 15. Bartoshuk L, Snyder DL, Grushka M, et al. Taste damage: we would not expect to see evidence of an IgM response previously unsuspected consequences. Chem Senses 2005; 30: years later. However, a “hit-and-run” mechanism of neu- suppl. (1): 218-9. ropathic pain and dysesthesia could be one of a number of mechanisms that could not be evaluated in this study (Accepted for publication May 26, 2006) of viral serology. Despite the fact that this study was limited by a small number of subjects, it was felt that HSV or other viral involvement by blood testing was un- likely to identify a viral causative agent for BMS and that either large, multi-center, epidemiologic studies are required or that different methodology including anatomi- cal examination of taste and pain fibers surrounding the fungiform papillae (14, 15), are required. While the patient sample size in this pilot study is small, the findings do not support a neuropathic role of HSV, CMV or VZV in the etiology of BMS.

References 1. Harold M and Nikolai B(eds). Classification of Chronic Pain. Descriptions of chronic pain syndromes and definitions of pain terms, Task Force on Taxonomy, 2nd Edition, IASP Press, Seattle. 1994; 74. 2. Grushka M. Clinical features of burning mouth syndrome. Oral Surg 1987; 63: 30-6. 3. Zakrzewska JM. The burning mouth syndrome remains an enigma. Pain 1995; 62: 253-7. 4. Ship J, Grushka M, Lipton JA, et al. Burning Mouth Syn- drome: An update. JADA 1995; 126: 843-53. 5. Grushka M, Katz RL and Sessle BJ. Spontaneous remission in burning mouth syndrome. J Dent Res 1986; 274 (abstr.). 6. Gilpin SF. Glossodynia. J Am Med Assoc 1936; 106: 1722-4. 7. Grushka M, Epstein J, Gorsky M. Burning Mouth Syndrome. Am Fam Physician 2002; 65:615-20. 8. Hashizume K. Herpes zoster and post-herpetic neuralgia. Jpn J Clin Med 2001; 59:1738-42. 9. Grushka M, Epstein JB and Gorsky M. Burning mouth syndrome: differential diagnosis. Dermatol Ther 2002; 15: 287- 91. 10. Lipton JA, Ship JA and Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Asso 1993; 124: 115-21. 11. Klausner JJ. Epidemiology of Chronic Facial Pain: diagnostic usefulness in patient care: J Am Dent Assoc 1994; 125: 1604-11. 12. Gorsky M, Silverman S Jr and Chin H. Clinical characteristics and management outcome in the burning mouth syndrome: An open study of 130 patients. Oral Surg Oral Med Oral Pathol 1991; 72; 192-5. 13. Grushka M, Epstein JB and Gorsky M. Burning mouth syndrome and other sensory disorders: A unifying hypothesis. Pain Res Manag 2003; 3: 133-5. 14. Becker TM, Lee F, Daling JR, et al. Seroprevalence of and risk factors for antibodies to herpes simplex viruses, hepatitis B, and hepatitis C among southwestern Hispanic and non- Hispanic white women. Sex Transmit Dis 1996; 23: 138-44.