Anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in 884 patients with burning mouth syndrome.

BACKGROUND/PURPOSE: Burning mouth syndrome (BMS) is characterized by burning sensation of the oral mucosa in the absence of clinically apparent oral mucosal alterations. This study evaluated the anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity in 884 BMS patients. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, GPCA levels in 884 BMS patients were measured and compared with the corresponding levels in 442 age- and sex-matched healthy control subjects. RESULTS: We found that 175 (19.8%), 143 (16.2%), 42 (4.8%), 20 (2.3%), 170 (19.2%), and 109 (12.3%) BMS patients had blood Hb, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 884 BMS patients had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 442 healthy control subjects (all P-values < 0.005). Of 175 anemic BMS patients, 95 had normocytic anemia, 27 had thalassemia trait-induced anemia, 21 had iron deficiency anemia, 15 had pernicious anemia, 15 had macrocytic anemia other than pernicious anemia, and 2 had microcytic anemia other than iron deficiency anemia and thalassemia trait-induced anemia. Burning sensation of oral mucosa (100.0%), dry mouth (48.1%), numbness of oral mucosa (30.7%), and dysfunction of taste (16.7%) were the four common symptoms in 884 BMS patients. CONCLUSION: BMS patients have significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects.

Plasma N-acylethanolamine and endocannabinoid levels in burning mouth syndrome: Potential role in disease pathogenesis.

OBJECTIVE: The objective was to measure endocannabinoid (eCB) ligands and non-cannabinoid N-acylethanolamine (NAE) molecules in plasma from individuals with burning mouth syndrome (BMS) and to determine whether plasma eCB/NAE levels correlated with pain, inflammation and depressive symptomatology in this cohort. STUDY DESIGN: Plasma content of the eCBs, anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG), and the NAE molecules, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were assessed in healthy subjects (n = 8) and in a cohort of newly diagnosed BMS patients (n = 9) using liquid chromatography-tandem mass spectrometry. Plasma eCBs and NAE profiles were correlated with self-rated oral cavity pain intensities, depressive symptomatology and plasma IL-8 levels. RESULTS: Plasma levels of PEA, but not OEA, AEA or 2-AG, were significantly elevated in patients with BMS, when compared to plasma from healthy individuals. Plasma PEA, OEA and AEA levels correlated with depressive symptomatology. CONCLUSIONS: This is the first evidence to indicate that circulating eCB/NAE levels are altered in BMS.

Burning mouth syndrome: results of screening tests for vitamin and mineral deficiencies, thyroid hormone, and glucose levels-experience at Mayo Clinic over a decade.

BACKGROUND: Burning mouth syndrome (BMS) is a disorder characterized by chronic mouth pain in the absence of objective clinical abnormalities. Vitamin or mineral deficiencies may have a role in BMS, but data regarding the prevalence and relevance of hematinic deficiencies are conflicting. We aimed to determine the frequency of specific laboratory abnormalities in patients with BMS. METHODS: We retrospectively reviewed the results of screening blood tests in patients with BMS at our institution between January 2003 and December 2013. RESULTS: Among 659 patients with BMS, the most common decreased values or deficiencies were vitamin D3 (15%), vitamin B2 (15%), vitamin B6 (5.7%), zinc (5.7%), vitamin B1 (5.3%), thyrotropin (TSH) (3.2%), vitamin B12 (0.8%), and folic acid (0.7%). Laboratory values for fasting blood glucose and TSH were increased in 23.7% and 5.2%, respectively. CONCLUSIONS: In patients with symptoms of BMS, our results suggest it is reasonable to screen for fasting blood glucose, vitamin D (D2 and D3 ), vitamin B6 , zinc, vitamin B1 , and TSH. Deficiencies of vitamin B12 and folic acid were rare (<1% abnormal).

Effective vitamin B12 treatment can reduce serum antigastric parietal cell antibody titer in patients with oral mucosal disease.

BACKGROUND/PURPOSE: Patients with serum antigastric parietal cell antibody (GPCA) positivity may have vitamin B12 deficiency and some oral symptoms. This study assessed the changes of serum GPCA titer in GPCA-positive patients after effective vitamin B12 treatment. METHODS: Two hundred and ten GPCA-positive oral mucosal disease patients became oral symptom free (complete response) after 1.0-67.1 months of treatment with regular and continuous intramuscular injection of vitamin B12 once per week. The changes of serum GPCA titers after treatment were evaluated in these 210 patients. RESULTS: We found a significant drop of the GPCA positive rate from 100% to 42.9% in our 210 complete response patients after effective vitamin B12 treatment (p < 0.001). When 210 patients were further divided into seven subgroups according to the low to high serum GPCA titers, we noted that the higher serum GPCA titers decreased to significantly lower levels after treatment in all seven subgroups (all p < 0.001). However, serum GPCA titers increased to significantly higher levels in 46 GPCA-positive control patients receiving only oral administration of two vitamin BC capsules (containing 10 µg of vitamin B12) plus deficient hematinic supplements per day after a follow-up period of 2.7-27 months. A maintenance vitamin B12 treatment once a month could retain the GPCA-negative status in 87% of treated-to GPCA-negative patients compared with those (10%) without further maintenance vitamin B12 treatment. CONCLUSION: Regular and continuous effective vitamin B12 treatment can reduce the relatively higher serum GPCA titers to significantly lower or undetectable levels in GPCA-positive patients.

Significant association of hematinic deficiencies and high blood homocysteine levels with burning mouth syndrome.

BACKGROUND/PURPOSE: Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa in the absence of clinically apparent mucosal alterations. In this study, we evaluated whether there was an intimate association of the deficiency of hemoglobin (Hb), iron, vitamin B12, or folic acid; high blood homocysteine level; and serum gastric parietal cell antibody (GPCA) positivity with BMS. METHODS: Blood Hb, iron, vitamin B12, folic acid, and homocysteine concentrations and the serum GPCA level were measured in 399 BMS patients and compared with the corresponding levels in 399 age- and sex-matched healthy control individuals. RESULTS: We found that 89 (22.3%), 81 (20.3%), 10 (2.5%), and six (1.5%) BMS patients had deficiencies of Hb (men: <13 g/dL, women: <12 g/dL), iron (<60 µg/dL), vitamin B12 (<200 pg/mL), and folic acid (<4 ng/mL), respectively. Moreover, 89 (22.3%) BMS patients had abnormally high blood homocysteine level and 53 (13.3%) had serum GPCA positivity. BMS patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency; of abnormally elevated blood homocysteine level; or of serum GPCA positivity than the healthy control group (all p < 0.001 except for vitamin B12 deficiency, for which p = 0.004). However, no significant difference in frequency of folic acid deficiency (p = 0.129) was found between BMS patients and healthy control individuals. CONCLUSION: We conclude that there is a significant association of deficiency of Hb, iron, and vitamin B12; abnormally high blood homocysteine level; and serum GPCA positivity with BMS.

Significant reduction of serum homocysteine level and oral symptoms after different vitamin-supplement treatments in patients with burning mouth syndrome.

BACKGROUND: Serum homocysteine level is a biomarker of cardiovascular disease. METHODS: In this study, 399 primary and secondary burning mouth syndrome (BMS) patients without or with hematinic deficiencies were treated with vitamin BC capsules plus none, one, or two deficient hematinics depending on the corresponding deficiency statuses of the patients. One hundred and seventy-seven patients showed complete remission of all oral symptoms after treatment. The blood homocysteine, vitamin B12, folic acid, iron, and hemoglobin concentrations at baseline and after treatment till all oral symptoms had disappeared in these 177 complete-response BMS patients were measured and compared by paired t-test. RESULTS: For BMS patients with concomitant deficiencies of vitamin B12 only (n = 48), folic acid only (n = 12), vitamin B12 plus folic acid (n = 9), or vitamin B12 plus iron (n = 15), supplementations with vitamin BC capsules plus corresponding deficient hematinics could significantly reduce the abnormally high serum homocysteine levels to normal levels after a mean treatment period of 5.4-8.2 months (all P-values < 0.01). For BMS patients without definite hematinic deficiencies (n = 62), supplementation with vitamin BC capsules only could also significantly decrease the relatively higher homocysteine levels to significantly lower levels after a mean treatment period of 10.2 months (P < 0.001). CONCLUSION: Specific supplementations with vitamin BC capsules plus none or corresponding deficient vitamin B12 and/or folic acid can reduce the abnormally high serum homocysteine levels to normal levels in BMS patients without or with deficiencies of corresponding hematinics.

Salivary cortisol, 17ß-estradiol, progesterone, dehydroepiandrosterone, and α-amylase in patients with burning mouth syndrome.

OBJECTIVE: The aim of this study was to investigate salivary markers related with burning mouth syndrome (BMS). MATERIALS AND METHODS: Thirty female patients with BMS and twenty female control subjects were included. Unstimulated (UWS) and stimulated whole saliva samples (SWS) were collected, and their flow rates were determined. Salivary levels of cortisol, 17ß-estradiol, progesterone, dehydroepiandrosterone (DHEA), and enzymatic activity of α-amylase were determined. Salivary transferrin level was measured to determine the level of blood contamination in saliva samples. RESULTS: The levels of all analytes in UWS were significantly correlated with those of SWS. The levels of 17ß-estradiol, progesterone, and DHEA in UWS were significantly correlated with age. Age-matched comparisons revealed that the patient group had significantly higher levels of cortisol in UWS and of 17ß-estradiol in SWS. When the patients were divided into older (≥60years) and younger (<60years) groups, the older group showed a significantly lower level of progesterone in UWS. There were no significant relationships between treatment efficacy and levels of salivary analytes. CONCLUSIONS: In conclusion, patients with BMS showed significantly higher levels of cortisol in UWS and of 17ß-estradiol in SWS compared with controls.

Zinc deficiency may be a cause of burning mouth syndrome as zinc replacement therapy has therapeutic effects.

BACKGROUND: Zinc is known to play an important role for growth and development, the immune response, neurological function, and reproduction. Although the etiology of burning mouth syndrome (BMS) is unknown, zinc deficiency may be implicated in the pathogenesis of BMS. The aim of this study was to demonstrate a causal relationship between zinc deficiency and BMS and to assess whether zinc replacement is an effective therapy for BMS. METHODS: Serum zinc level was evaluated in 276 patients with BMS. To assess the therapeutic effect of zinc replacement, patients with zinc deficiency were administered a zinc supplement (14.1 mg/day). Pain intensity 6 months after zinc replacement was evaluated using an 11-point numerical scale. We also developed an animal model of zinc deficiency to assess the effects of zinc deficiency on the oral mucosa. RESULTS: Of the 276 patients with BMS, 74 (26.8%) had low serum zinc levels. Zinc replacement therapy lowered the mean numerical pain scale in these patients from 8.1 to 4.1, compared with a mean decrease from 7.7 to 6.7 in a control group (P = 0.004). In our animal model of zinc deficiency, the main pathologic findings were hyperkeratinization and increased mitosis on the dorsum of the tongue, although there were no gross oral mucosal lesions. CONCLUSIONS: Zinc deficiency might play a role in some patients with BMS. In such patients, appropriate zinc replacement therapy is effective in relieving symptoms.

A case-control study on etiological factors involved in patients with burning mouth syndrome.

OBJECTIVE: To evaluate and analyze the risk factors for burning mouth syndrome (BMS). METHODS: Eighty-seven consecutive patients with BMS and a randomly selected control group (n = 82) were comprehensively investigated with a self-designed questionnaire, Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). A complete blood count and serum sex hormone were also examined in patients with BMS and control subjects. All the data obtained were transferred to a data bank and analyzed statistically in SPSS 11.5 for windows. RESULTS: No statistical difference between the BMS group and the control group was found in blood analyses including white blood cell count, red blood cell count, hemoglobin and platelet count. Among the menopausal or postmenopausal women with BMS, the follicle stimulating hormone (FSH) level was significantly higher, but the estradiol level was significantly lower. The BMS group reported adverse life events more frequently than the control group. Patients with BMS significantly exhibited symptoms of somatization, and both the scores of anxiety, depression in patients with BMS were higher than those of the control group (P < 0.05). A regression equation which included six variables had been established by using logistic regression analysis, indicating that the habit of tongue thrusting, lip sucking, periodontitis, smoking, outcome of recent medication, depression were the principal risk factors, among which tongue thrusting was the most significant. CONCLUSION: Our study indicated that BMS may be of psychological origin, and the measures such as refraining from oral parafunctional activities, removing local irritating factors, stopping smoking, good mental health status could help in the prevention of BMS.

Serum cytokine and T regulatory cell levels in patients with burning mouth syndrome.

BACKGROUND: Burning mouth syndrome is a disorder usually associated with an unexplained, prolonged sensation of burning inside the oral cavity. Although the etiology is unknown, neural and psychologic factors and cytokines may be implicated in the pathogenesis of burning mouth syndrome. The aim of this study was to investigate the relationship between serum cytokine and T regulatory cell levels in patients with burning mouth syndrome with regard to depression and anxiety. METHODS: Thirty patients with burning mouth syndrome and 30 matched controls participated in the study. Serum cytokine levels were measured with cytometric bead array and T regulatory cells were defined as CD4(+)CD25(+)Foxp-3(+) cells by flow cytometry. The level of anxiety and depression were analyzed by means of the Speilberger State-Trait Anxiety Inventory and Zung Self-Rating Depression Scale. Visual analogue scale was used in the quantification of burning levels of patients. RESULTS: Serum IL-2 and TNF-alpha levels were significantly decreased in patients with burning mouth syndrome compared with controls [mean 16.79 +/- 8.70 vs. 37.73 +/- 41.05 pg / ml (P < 0.05) and mean 39.09 +/- 29.40 vs. 70.83 +/- 42.44 pg / ml (P < 0.01) respectively]. CONCLUSIONS: IL-2 and TNF-alpha might play a role in burning mouth syndrome. Burning mouth syndrome may occur as a sign of predisposition to autoimmunity. Presence of low levels of CD28(+) supports the provision that BMS might be a pre-autoimmune disease.

Serum interleukin-6 in patients with burning mouth syndrome and relationship with depression and perceived pain.

OBJECTIVE: To examine alteration of serum interleukin-6 and its clinical significance in burning mouth syndrome (BMS) patients. METHODS: 48 BMS patients and 31 healthy controls participated in the study. Serum interleukin-6 was measured by means of ELISA. Hamilton rating scale of depression (HRSD) and visual analogue scale (VAS) were used to quantitate depressive status and pain levels of subjects, respectively. RESULTS: 15 (31%) patients displayed substantial depressive symptoms (HRSD > or = 16). HRSD scores of patients were significantly higher than controls and positively correlated to their VAS values (P = .002). Serum interleukin-6 in patients was much lower than controls and negatively correlated to their VAS values (P = .011). However, no significant relations were found between interleukin-6 and HRSD scores (P = .317). CONCLUSIONS: Serum interleukin-6 in patients with burning mouth syndrome is decreased and negatively correlated to chronic pain. Both psychological and neuropathic disorders might act as precipitating factors in BMS etiopathogenesis.

[Correlations among mood disorder, serum interleukin-2 and interleukin-6 in patients with burning mouth syndrome].

OBJECTIVE: To examine serum IL-2 and IL-6 levels in BMS patients with or without depression and make clear the relationship between serum IL-2, IL-6 and mood disorder. METHODS: Serum IL-2 and IL-6 were examined in 48 BMS patients by means of ELISA. The Hamilton Depression Rating Scale (HDRS) was used to evaluate the depressive symptomatology. RESULTS: There was no significant difference in serum IL-2 and IL-6 among BMS patients with or without depression. Mood disorder was not correlated to serum IL-2 and IL-6, but positively correlated to pain levels. CONCLUSION: Depression status may not influence serum IL-2 and IL-6 levels significantly, but it has a relationship with BMS. The HDRS can be used to determine depression status in BMS patients in order to help clinical treatment.

[Role of total IgE in unspecified burning oral symptoms. Serum and salivary comparative levels in a case-control study]. / Ruolo delle IgE totali nella sintomatologia urente del cavo orale. Titolazione comparata dei livelli di IgE sieriche e salivari in uno studio caso-controllo.

BACKGROUND: Oral burning symptom is often taken into account in Oral Medicine for its high prevalence and respective management problems. The clinical evidence that exclusion from the diet of some foods, considered potentially allergenic, would relieve this symptom represented the rationale of the present study. So, the main aim was to investigate the role of the IgE-mediated pathogenesis in patients with unspecified oral burning symptoms and positivity to the challenge with some foods. METHODS: Comparative levels of total serum and salivary IgE were investigated in 97 patients referred to the Sector of Oral Medicine (University of Palermo), of whom 50/97 as a Test group, symptomatic for burning complaint and affected by burning mouth syndrome (BMS), oral lichen planus (OLP) and recurrent aphtous stomatitis (RAS) and 47/97 as Control group, non-symptomatic, matched for gender, age-decade group and affected with different oral mucosal lesions. RESULTS: In the Test group, the following results were found: total average values for serum IgE of 71.5 (SD+/-100.3; range 4-424) and for salivary IgE of 8.7 (SD+/-30.4; with range 0-218). In the Control group total average values for serum IgE were 85.8 (SD+/-210.7; range 5-1390) and for salivary IgE 20.6 (SD+/-66.6; range 2-408). Statistical evaluation of serum and salivary total IgE levels did not find any significant difference in the Test group vs controls (p>0.2) with respect to gender, age-decade or different type of oral disease with burning symptoms. Of note, in the Test group a positive correlation was found between serum IgE levels and salivary total IgE. CONCLUSIONS: On the basis of our results, no evidence of IgE-mediated allergic process can be suggested in such a generic oral burning symptom, even after a positive challenge for selective diet.

Evaluation of tumour markers in patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is an enigmatous condition both for the patient and the clinician, and is diagnosed on the basis of the patient's symptoms when they have on examination an apparently healthy looking oral mucosa. A variety of local and systemic factors are known to contribute to burning mouth syndrome. Some authors reported that underlying malignancy could be a possible cause for BMS. In 23 patients with burning mouth syndrome as well as in 20 age, sex, and race matched healthy controls levels of tumour markers-CEA, CA 19-9, AFP, and CYFRA 21-1-were determined from sera. Immunoradiometric assay (IRMA) for detection of ELSA-CEA, ELSA-CA 19-9, ELSA 2-AFP, ELSA-CYFRA 21-1 (CIS bio international, ORIS group, France) was used. Statistical analysis showed no significant differences in the level of tumour markers CEA, CA 19-9, AFP, CYFRA 21-1 in patients with burning mouth syndrome when compared to the healthy controls. We can conclude that evaluation of tumour markers in patients with burning mouth syndrome is not useful and in terms of cost-benefit this investigation should not be performed in patients with burning mouth syndrome.

Lack of association between burning mouth syndrome and hematinic deficiencies.

The aim of our investigation was to evaluate possible connection between burning mouth syndrome and hematinic deficiencies, a hypothesis previously reported in the literature with contradictory results. Serum levels of iron, vitamin B12, folic acid, calcium and magnesium were determined in 41 (aged 31-87 years, mean 68,7 yrs) patients with burning mouth syndrome and 35 matched controls (35-83, mean 63 yrs). Serum iron levels were determined according to Fairbanks and Klee. Levels of vitamin B12 and folic acid were determined on commercially available kits (Imx12 and Imx folate assay, Abbot Park lab, IL, USA) on Imx analyser. Calcium and magnesium levels were determined using atomic absorption spectrophotometry. No statistically significant differences in serum levels of iron, folic acid, calcium and magnesium were found between patients with burning mouth syndrome and controls. Statistically significant lowered vitamin B12 levels were found in patients with burning mouth syndrome. Our results suggest that serum deficiencies of iron, folic acid, calcium and magnesium are not etiological factor in patients with burning mouth syndrome.

The secretion of parotid saliva as stimulated by 10% citric acid is not related to precipitating factors in burning mouth syndrome.

Burning mouth syndrome (BMS) is known to have multiple precipitating factors and exists in various clinical subtypes. If salivary gland function was compromised in BMS it could help explain the link with diverse precipitating factors. This study quantified stimulated right and left parotid flow rates (SPFR) in 114 patients with BMS. It also attempted to correlate SPFR with haematinic parameters, oral candidal carriage, concurrent drug therapy and BMS subtype. No relationship was found between haematinic parameters and SPFR nor between SPFR and oral candidal carriage. Patients with Type 2 BMS had a significant reduction in SPFR. Antidepressant medication was associated with reduced SPFR but there was no such association with either tranquillisers or hypnotics. These results provide evidence of reduced parotid gland function in Type 2 BMS and a role for antidepressant medication in reducing SPFR.

[Study on psychoprophylaxis and monoamines neurotransmitter of patients with burning mouth syndrome].

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic ache disease, usually occurring in middle aged and old women. This study sought to understand the psychopathologic aspect and monoamines neurotransmitters in the plasma of the patients with BMS. METHODS: Thirty cases were selected (26 females, 4 males); 30 normal control subjects were similar to the BMS cases on age and sex. All subjects were required to complete the Eysenck personality questionnaire (EPQ), and the Self-report Symptom Inventory, Symptom Check List-90 (SCL-90) questionnaire. In case a subject's L (lie) score exceeded 50, she (he) would be removed from the test. 2 ml of blood was drawn from the subject under restine conditions with a fast in the morning to examine norepinephrine and epinephrine contents by high efficient liquid chromatography. Chi-square test, analysis of variance and t'-test were performed. RESULTS: The BMS group had higher scores of nervousness (N) and poikilergasia (P) and lower score of extro/introversion (E) as compared with the control (P < 0.05). The personality types in BMS group were focused on introversion and instability, but in the control group the types were focused on extroversion and stability (P < 0.05). The scores of 9 emotional factors of BMS group were significantly higher than those of the control group (P < 0.05), which indicated that the BMS patients had suffered from serial psychic disorders. The level of plasma norepinephrine in the BMS patients was higher than that of the control (P < 0.01). CONCLUSION: The personality of BMS patients raised body response to harmful stimulations, and obvious psychic disorders in the patient may cause the functional disorders in central and sympathetic nervous systems, which may be associated with BMS' occurrence.

Serum zinc levels in patients with burning mouth syndrome.

The serum zinc levels were measured by atomic absorption spectrophotometry in 30 patients with burning mouth syndrome, (BMS) and in 30 control subjects with clinically healthy oral mucosa. The mean value of serum zinc levels in the patient group was found to be significantly lower (mean +/- SD = 12.13 +/- 1.40 mumol/L) than the mean value of serum zinc levels in the control group (mean +/- SD = 12.89 +/- 1.62 mumol/L; p less than 0.05). The number of subjects with serum zinc levels less than the minimum normal value (less than 11 mumol/L) was higher in the patients with BMS (30%) than in the control subjects (10%). These results suggest that in some patients low serum zinc levels may be associated with BMS. However, the number of patients with BMS was too small to allow definite conclusions.