Diagnostic algorithm
Patients suspected of BMS were examined and diagnosed in our department according to the algorithm shown in Fig. 1 and the criteria of The International Classification of Headache Disorders (ICHD-3) [10]. Patients were considered to have secondary BMS if systemic and psychosocial factors associated with secondary BMS and structural disorder in the oral cavity were found during examination. Patients with residual symptoms after antifungal therapy and replacement therapy for deficiency factors such as trace metals and vitamin B12 were diagnosed as primary BMS when blood tests were normal.
This retrospective study was conducted with the approval of the Hokkaido University Hospital Independent Clinical Research Review Committee (Approval No. 019-0044).
Patients
The data of 340 patients who were suspected to have primary or secondary BMS were reviewed at the Department of Oral Medicine, Hokkaido University Hospital between January 2013 and July 2019 (Fig. 2). Patients with an underlying medical condition, based on interview, or any abnormalities found through our diagnostic algorithm were excluded (n = 258) because of possible secondary BMS. The details of secondary BMS as classified according to the classification proposed by Balasubramaniam et al. [11] are as follows: local factors for 40, systemic factors for 183, psychosocial factors for 51. Some patients had multiple factors, and 15 and 20 patients were diagnosed with secondary BMS caused by oral candidiasis and trace metal deficiency, respectively. Patients were excluded if rikkosan was not used (n = 8) or they were treated with rikkosan in combination with other agents (n = 29). Patients were excluded whose treatment outcome was unclear (n = 1) or whose numerical rating scale (NRS) score was not described (n = 12). Thirty-two patients who had clear medical records of their treatment were enrolled in this study.
Treatment algorithm for primary BMS
We first explained to each participant the pathology of primary BMS. After explaining that there was no need for immediate surgical treatment and that the disease is non-fatal, we initiated pharmacotherapy according to each patient’s preference and did follow-ups once or twice a month. In our department, we often choose Japanese Kampo medicines as single agents for the initial pharmacotherapy because they have relatively few side effects and are easy to administer to elderly people [12]; however, anxiolytics and antidepressants may be ultimately selected for treatment based on the patient’s preference.
Treatment dosage and administration
In this study, we administered single-agent rikkosan as a mouthwash for gargling (2.5 g rikkosan [Tsumura, Tokyo, Japan] dissolved in 50 mL hot water) three times daily (7.5 g/day).
Study variables
Various factors, such as patient characteristics (age, sex) and clinical parameters (duration of illness, site of BMS, dosing period, treatment outcome, and side effects), were retrospectively examined. The duration of the disease was defined as the time from when the patient became aware of the symptoms to when the patient visited our department.
Evaluation criteria of the therapeutic effects
The effectiveness of the treatment was assessed by referring to changes in NRS scores. NRS scores were evaluated by asking patients to assess the degree of pain they were currently experiencing, with 0 being no pain and 10 being the worst possible pain. NRS scores were measured at the time of the first visit and at 1 month after the initiation of gargling with rikkosan.
Statistical analysis
Statistical analyses were performed using JMP Pro Version 14.0 (SAS Institute, Cary, NC) and included Wilcoxon rank test. Wilcoxon rank test was performed to assess significant differences in mean NRS scores at different time intervals. P < 0.05 was considered statistically significant.