Aetiology and therapeutics of burning mouth syndrome: an update Introduction

Aetiology and therapeutics of burning mouth syndrome: an update Introduction
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  Review article Aetiology and therapeutics of burning mouth syndrome: anupdate Juliana Cassol Spanemberg, Karen Cherubini, Maria Antonia Zancanaro de Figueiredo,Liliane Soares Yurgel  and  Fernanda Gonc¸alves Salum Stomatology and Bucomaxillofacial Cancer Prevent Division, Sa ˜ o Lucas Hospital, Pontifical Catholical University of Rio Grande do Sul(PUCRS), Porto Alegre, Brazil doi: 10.1111/j.1741-2358.2010.00384.x  Aetiology and therapeutics of burning mouth syndrome: an update Objective:  To provide a review on the aetiology and therapeutic options for the management of patientswith burning mouth syndrome (BMS). Background:  BMS is a chronic disorder that frequently affects women and is characterised by burningsymptoms of the oral mucosa without clinical signs. This syndrome has a complex and multifactorialcharacteristics, but its aetiology remains unknown and this makes it difficult with regard to the treatmentand management of such patients. Despite not being accompanied by evident organic changes and notpresenting risks to health, BMS can significantly reduce the quality of life for patients. Methods and materials:  The article reviews the literature regarding aetiologic factors, clinical implica-tions and treatment of BMS. Conclusion:  The involvement of neurological, emotional and hormonal alterations is proposed in BMSaetiology. However the mechanisms of its development are complex and not completely understood.Tricyclic antidepressants, benzodiazepines and antipsychotic drugs are the most accepted options intreatment and show variable results. The correct diagnosis of BMS and the exclusion of possible local orsystemic factors that can be associated with the symptoms are fundamental. It is also important to evaluatethe quality of life for these patients to recognise the potential impact of this condition on their lives. Keywords:  burning mouth syndrome, psychological profile, aetiology, treatment.  Accepted 6 January 2010 Introduction Burning mouth syndrome (BMS) is a complexchronic disorder characterised by symptoms of burning, pain or itching of the oral mucosa, with-out observable changes, laboratory analysis ormodifications of salivary flow rate. 1–5 This syn-drome shows a higher prevalence in middle-agedand elderly women, 6–8 with the most frequentlyaffected sites being the tongue, hard palate andlower lips. 9,10 The episodes of BMS are spontaneous and thesymptoms range in severity; while some patientscomplain of moderate discomfort, others haveunbearable pain. 3,9 Moreover, symptoms of dys-geusia and xerostomia are common and associatedwith similar sensory abnormalities. 11–13 Many studies fail to distinguish properly between burning complaints and the true syndrome. Severalcriteria should be observed, as burning mouthsymptoms are common and can be promoted bylocal or systemic factors, which do not characterisetrue BMS. These clinical or laboratory conditionsassociated with burning mouth include candidiasis,geographic tongue, hyposalivation, oesophagealreflux, parafunctional habits, diabetes, nutritionaldeficiencies (iron, folate, B 1 , B 2 , B 6 , B 12 ) andadverse effects of certain drugs. In such cases, ifthe cause is removed, there is relief of thesymptoms. 14,15 Despite not being accompanied by evident or-ganic changes and not presenting risks to health,this syndrome can significantly reduce quality oflife in patients. 16 Individuals with BMS frequently 84    2012 The Gerodontology Society and John Wiley & Sons A/S,  Gerodontology  2012;  29 : 84–89  have a history of numerous medical and dentalconsultations, seeking a cure that still does notexist. In this study, the literature has beenreviewed, analysing aspects related to the aetiologyand therapeutic options for the management ofBMS patients. Aetiology Many studies have investigated the relationship between burning symptoms and oral lesions,candidiasis, geographic tongue, hyposalivation orsystemic diseases such as diabetes and nutritionaldeficiencies. 6,17–19 However, these studies will not be discussed as the evidence does not characterisethe true syndrome. Amongst the possible causes ofBMS, hormonal, 20 neuropathic 21,22 and psycho-logical factors stand out, as well as stress, anxietyand depression stand out. 2,10,23,24 Evidence suggests that disorders of the hormone balance may be related to BMS in women as thedisease is more frequent during and after meno-pause. 25,26 According to Wardrop  et al., 27 BMS,depression and anxiety can be the product of acommon factor, an endocrinological disorder could be the cause of these alterations in women fol-lowing menopause. Symptoms of BMS were foundin 46% of women at menopause and approxi-mately 60% showed relief after hormonereplacement. Forabosco  et al. 20 attributed the reliefof oral discomfort following hormone therapy, tothe presence of oestrogen receptors on the oralmucosa. On the other hand, Tarkkila  et al. 28 evaluated the relation between oral discomfortand menopause in 3173 patients, verifying that8% of these women exhibited burning sensationsof the oral tissues. However, hormone replace-ment therapy did not prevent the occurrence ofsymptoms.Peripheral and central nervous system dysfunc-tion has been proposed in the pathophysiology ofBMS. 21,22,29–31 Lauria  et al. 21 described a trigeminalsmall-fibre sensory neuropathy in patients withBMS. Superficial biopsies of the lateral aspect of theanterior tongue were obtained, with the density ofepithelial nervous fibres quantified and BMSpatients showed a significantly lower density ofepithelial nerve fibres than controls. Moreover, theepithelial and sub-papillary nerve fibres exhibiteddiffuse morphological changes reflecting axonaldegeneration.Albuquerque  et al. 22 investigated, by functionalmagnetic resonance imaging, brain activity inpatients with BMS following thermal stimulation ofthe trigeminal nerve. BMS patients had less volu-metric activation throughout the entire braincompared to the control group, suggesting that brain hypoactivity can be an important feature inthe pathophysiology of this syndrome.According to Guimara ˜ es  et al. 32 genetic poly-morphisms associated with an increase of inter-leukin-1 b , a pro inflammatory cytokine that has been associated with pain modulation, can beimplicated in the aetiology of BMS. Guarneri et al. 33 suggested that changes in the pain percep-tion, neural transmission dysfunction, increases inexcitability or negative involvement of trigeminalvascular system can be mechanisms associated withthe syndrome.Several studies have demonstrated that thepsychological profile of patients with BMS followsthe same pattern, most of them showing personal-ity and mood changes. 2,10,23,34 Patients with BMSshow many adverse events during their lives com-pared to control subjects. 10 Pokupec-Gruden  et al. 23 verified in a case-controlled study that anxiety anddepression were most common in patients withBMS. Femiano  et al. 2 reported that subjects withthe disorder exhibit decreased self-esteem, absenceof solid and satisfactory personality and that thissyndrome was preceded by significant losses andchanges in their lives. To Palacios-Sa´ nchez  et al., 35 there was a clear association between life changesand the establishment of the syndrome. Patientswith BMS showed higher scores of anxiety andsalivary cortisol levels than control patients. 34 Therapeutic approaches Treatment of BMS is usually directed to manage-ment of the symptoms, but local factors that couldincrease the sensation of oral burning should beeliminated, such as alcohol, spicy foods and aciddrinks which act as irritants on oral mucosa. It isnecessary to investigate whether the patient’ssymptoms are being caused by parafunctionalhabits, galvanic current, mechanical irritation ordenture allergy. 6,17 Treatment or elimination ofthese factors has been shown to result in a clinicalimprovement. 20 If patients still have the symptomsafter the removal of potential of dental causes, drugtherapy may be instituted. 18 Some studies relate to the topical use of capsai-cine ( Capsicum frutescens  L.) to control neuropathicpain, as this drug acts on the sensory afferentneuron and can be used as an analgesic. 25,36–38 However, capsaicine had its use reduced as it pro-moted an increase in the burning sensation at the beginning of the treatment. 25,36 Anaesthetics suchas lidocaine (2%) have been used topically as a   2012 The Gerodontology Society and John Wiley & Sons A/S,  Gerodontology  2012;  29 : 84–89  Aetiology and therapeutics of burning mouth syndrome  85  palliative method to reduce pain symptoms ofpatients with the syndrome. 25 Tricyclic antidepressants, benzodiazepines andantipsychotic drugs have also been investigated andare the most accepted options in BMS treatment,even when causing hyposalivation and xerosto-mia. 26,39 The benzodiazepine, clonazepam, haspromotedreliefoftheburningsymptomswhenusedtopically. 40 Paroxetine,atricyclicantidepressantwasused for 12 weeks in patients with BMS but not in acontrolled study. 41 Approximately 80% of patientsreportedareductionofsymptoms,withlittleadverseeffect, suggesting that this drug could be a thera-peutic option. Ueda  et al. 42 used the antipsychotic,olanzapine (a potent antagonist of dopamine, nor-epinephrine and serotonin neuron receptors) andfound a reduction of symptoms in two patients withthe syndrome. However, controlled studies should be carried out to confirm the effectiveness of thisdrug and to elucidate its mechanisms of action.Trazodone, a drug used to treat depression,psychiatric and sleep disturbances did not showsatisfactory results for the relief of oral burningsymptoms. 43 This drug is considered an atypicalanti-depressive agent as it promotes the pre-syn-aptic inhibition of serotonin, blockage of 5-HT2Aand 5HT2C serotoninergic receptors on neuronpost-synapse. 44 Alpha-lipoic acid (ALA) can be employed inpatients with BMS by acting as a neuro-protectivehelping with neural damage. 2 Patients treated forpsychotherapy and those who received 200 mg ofALA three times a day, for 2 months, obtainedsignificant improvement of BMS symptoms. Themost impressive results were obtained in the grouptreated with ALA and psychotherapy simulta-neously. According to the researchers, there was aneed to associate the psychotherapy with the drugs,as psychogenic alterations are strongly related toBMS. Bergdahl  et al. 45 employed the cognitive behaviour therapy for BMS once a week for12-15 weeks and a decrease in pain intensity wasobserved immediately after therapy and in a follow-up of 6 months.There are also a few placebo controlled studiesfor BMS treatment and these studies are summar-ised in Table 1. Discussion Before specific treatment, a patient with BMS willrequire a diagnosis. It is fundamental that theprofessional explains the nature of BMS and itsimplications to the patient. The affected subjectsneed to admit to the presence of this disorder andlearn to live with it, being aware that a solutionmay not be found.Despite being a frequent disorder, the cause ofBMS remains unknown and of multifactorial aeti-ology, with the involvement of neurological,emotional and hormonal alterations. 10,22 Becauseof its chronic nature, varied treatments aredescribed in the literature in order to try andreduce the burning sensations. However, there area few placebo controlled studies that show signifi-cant results in patients with the syndrome. Thetopical use of clonazepam is a therapeutic option asit acts as an agonist of Gamma-Amino Butyric acid(GABA) receptors, having as its main property thelight inhibition of central nervous system functionsproducing an anticonvulsivant action, light seda-tion, muscular relaxation and tranquiliser effect.Gremeau-Richard  et al. 40 suggest that the action ofthis drug is related to peripherical nervous systemdysfunctions in patients with the syndrome and thepresence of GABA receptors in peripheral tissues.When used topically, this drug does not show theadverse effects of its systemic use.ALA has been investigated for BMS treatment because of its neuro-protection properties, how-ever, studies with this drug showed controversialresults. Femiano  et al., 29 Femiano and Scully, 30 andGombos and Scully observed improvement of the burning symptoms in 76 and 97% of cases, whileCarbone  et al., 46 Lo´ pez-Jornet  et al. 47 and Caval-canti and Silveira 15 did not find significantimprovement. The conflicting results could beexplained by the different scales used to measurethe intensity of symptoms. The relief of BMSsymptoms is described when using antidepressantsystemic drugs such as paroxetine and olanza-pine. 41,42 However, placebo controlled studiesshould be carried out to prove the efficacy of thesedrugs in BMS treatment.The psychological profile of BMS individuals ischaracteristic of people with high levels of stress,anxiety and depression, 2,10,23,34,45 for this reasonmany studies suggest psychotherapy for syndromemanagement. 2,10,45 Patients with BMS reportedconsultations with several professionals, resulting inan increase in anxiety and depression regarding theirphysical health. Albuquerque  et al. 22 demonstratedthatthethalamusinpatientswithBMSishypoactive,which could be related to the psychological anguishexhibited by these individuals or to the chronic painalready demonstrated in previous studies.The management of patients with BMS is difficultand canbe frustrating. The correct diagnosis of BMSand the exclusion of possible local or systemicfactors are fundamental. The complex mechanisms   2012 The Gerodontology Society and John Wiley & Sons A/S,  Gerodontology  2012;  29 : 84–89 86  J.C. Spanemberg et al.  of BMS need to be investigated to establish aneffective treatment for this disorder. It is alsoimportant to evaluate the quality of life for thesepatients recognising the impact that this conditionhas on their lives, as symptoms can be present formany years. 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