Journal reading 報告者： PGY2 曾智皇 報告日期 : 指導老師 : 林立民 醫師 陳玉昆 醫師

Introduction Burning mouth syndrome (BMS) is typically described by the patients as a burning sensation of the oral mucosa  absence of clinically apparent mucosal alterations Overall prevalence ranging from 0.7% to 7% Prevalence up to 12% to 18% for post- menopausal women with BMS

BMS often affects the tongue (particularly the tip and lateral borders), lips, and hard and soft palate Unremitting oral mucosal pain, dysgeusia, and xerostomia

Diagnostic criteria Oral burning or pain  Unremitting for at least 4–6 months  Continuous throughout almost all the day  Seldom interferes with sleep and never worsens  May be relieved, by eating and drinking

Other oral symptoms:  Dysgeusia  Xerostomia  Presence of sensory/chemo-sensory anomalies  Mood changes  Disruptions in patient personality traits Can not have any signs of oral mucosal pathology !!

Detailed review of patient’s medical and dental histories Careful analysis of data obtained from physical and laboratory examinations

Classification and subtypes Lopez-Jorne et al  Type 1 BMS: Pain-free waking  gradually increasing  reaching its peak intensity by evening 35% Linked to systemic disorders such as nutritional deficiency, diabetes mellitus

Type 2 BMS: Continuous symptoms throughout the day 55% Usually associated with psychological disorders Type 3 BMS: Intermittent symptoms 10% Show allergic reactions

Scala et al. classified BMS into 2 clinical forms  1. Primary BMS: a.Essential or idiopathic b.Peripheral and central neuropathological pathways are involved 2. Secondary BMS: a.Caused by local, systemic or psychological factors

Primary BMS 1 st subgroup: Peripheral small-diameter fiber neuropathy of intraoral mucosa (50–65%) 2 nd subgroup: Subclinical lingual, mandibular, or trigeminal system pathology (20–25%) 3 rd subgroup: Hypofunction of dopaminergic neurons in the basal ganglia (20–40%)

Lauria et al  Significantly lower density of epithelial nerve fibers in patients with BMS than in control subjects Just et al  Patients with BMS exhibit a decreased somatosensory and gustatory perception Albuquerque et al  Patients with BMS had less volumetric activation throughout the entire brain

Secondary BMS Local factors: poorly fitting prostheses, parafunctional habits, dental anomalies, allergic reactions, infection, chemical factors, galvanism, taste alterations, and xerostomia Systemic factors: endocrine alterations (hypothyroidism, diabetes, and menopause), vitamin B complex, iron and zinc deficiencies, anemia, gastrointestinal anomalies, medication, Sjogren’s syndrome, and esophageal reflux

Psychological factors: anxiety, depression, compulsive disorders, psychosocial stress, and cancerphobia

Netto et al  Significant association of the presence of gastrointestinal diseases and urogenital diseases with BMS  Significant correlation between the intake of H-2 receptor antagonist or proton-pump inhibitor and BMS

Gao et al  87(BMS) and 82  No statistical difference in blood analyses (including white blood cell count, red blood cell count, hemoglobin (Hb), and platelet count ) between the BMS and control groups  Significantly higher serum follicle-stimulating hormone level and a significantly lower serum estradiol level in the menopausal or post- menopausal women with BMS

 Anxiety and depression scores in patients with BMS are higher  Habit of tongue thrusting, lip sucking, periodontitis, smoking, outcome of recent medication, and depression are the principal risk factors for the BMS

Lin et al  Patients with BMS had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency  Abnormally elevated blood homocysteine level  Serum GPCA (gastric parietal cell antibody) positivity

Boras et al  Significantly lower serum neurokinin A is found in patients with BMS  Indicating an inefficient dopaminergic system in patients with BMS

Pekiner et al  Significantly lower serum IL-2 and TNF-a levels in patients with BMS  Significantly lower mean salivary Mg level in patients with BMS

Maragou and Ivanyi, Cho et al  Significantly lower mean serum zinc level in patients with BMS Pokupec-Gruden et al  Anxiety and depression are most common in patients with BMS

General consideration for treatment of BMS Detailed review of patient’s medical and dental histories and a careful analysis of patient’s data  setting up a therapeutic regimen Treatment or elimination of these factors (local, systemic, psychological) usually results in a significant clinical improvement

If patients still have the symptoms  drug therapy should be instituted The custom-made or combination therapy for each patient with BMS  the greatest benefit to the patient and lessen the treatment duration

1.Vitamin supplement treatment 2.Zinc replacement treatment 3.Hormone replacement treatment 4.Topical drug treatment 5.Systemic drug treatment

1.Vitamin supplement treatment 2.Zinc replacement treatment 3.Hormone replacement treatment 4.Topical drug treatment 5.Systemic drug treatment

Vitamin supplement treatment Sun et al Vitamin BC capsules plus relatively high doses of corresponding deficient hematinics  a. reduce the abnormally higher mean serum homocysteine levels b. raise the corresponding lower mean deficient hematinic and Hb levels

1.Vitamin supplement treatment 2.Zinc replacement treatment 3.Hormone replacement treatment 4.Topical drug treatment 5.Systemic drug treatment

Zinc replacement treatment Cho et al Evaluated the serum zinc level in 276 patients with BMS Zinc replacement therapy in BMS patients with zinc deficiency is effective

1.Vitamin supplement treatment 2.Zinc replacement treatment 3.Hormone replacement treatment 4.Topical drug treatment 5.Systemic drug treatment

Hormone replacement treatment Wardrop et al  prevalence of oral discomfort is significantly higher in perimenopausal and post- menopausal women  43% 6% Forabosco et al

1.Vitamin supplement treatment 2.Zinc replacement treatment 3.Hormone replacement treatment 4.Topical drug treatment 5.Systemic drug treatment

Topical drug treatment Epstein and Marcoe Gremeau-Richard et al Peripheral nervous system dysfunctions in patients with BMS

Sardella et al Lopez-Jornet et al Topical Aloe vera has been shown to promote the healing process in the treatment of burns, psoriasis, and oral lichen planus

1.Vitamin supplement treatment 2.Zinc replacement treatment 3.Hormone replacement treatment 4.Topical drug treatment 5.Systemic drug treatment

Systemic drug treatment Petruzzi et al Its use is not recommended for extended treatment Grushka et al Heckmann et al

Ko et al Investigated outcome predictors of clonazepam therapy Amos et al Combined topical and systemic clonazepam administration is an effective regimen for treatment of BMS

Femiano et al Antioxidant mitochondrial coenzyme  neuroprotective effect Marino et al prolonged therapy in chronically affected patients with BMS is needed for maintaining a more permanent effect

Maina et al No serious adverse effects are referred in any of the three groups Rodriguez-Cerdeira and Sanchez-Blanco Amisulpride seems to be effective and well tolerated

Yamazaki et al A tricyclic antidepressant The side effects are minor and transient and no serious safety issues are observed Bergdahl et al

Summary BMS is probably of multifactorial origin and may be idiopathic Clinicians should first try to identify the precise causative factors for the BMS If patients still have the symptoms after the removal of potential causes, drug therapy should be instituted

Previous clinical trials have found that drug therapy with capsaicin, alpha-lipoic acid, clonazepam, and antidepressants  relief of oral burning or pain symptom Psychotherapy and behavioral feedback may also help eliminate the BMS symptoms

Thank you for your attention