B u r ni n g M o u t h Sy n d ro m e

Brittany Klein, DDSa, Jaisri R. Thoppay, DDS, MBA, MSb,

Scott S. De Rossi, DMD, MBAc, Katharine Ciarrocca, DMD, MSEdd,*

KEYWORDS
 Oral burning  Dry mouth  Glossodynia  Burning mouth syndrome  Oral dysesthesia

KEY POINTS
 Burning mouth syndrome (BMS) is a chronic condition characterized by a burning sensation of the
intraoral mucosa in the absence of a local or systemic cause.
 A diagnosis of BMS should be made only after a thorough history, clinical examination, and indi-
cated laboratory studies have ruled out local or systemic cause.
 Despite advances in the understanding and treatment of BMS, it remains a challenging condition for
both patients and providers.
 Some patients experience at least partial remission of symptoms with or without treatment, but, for
many, symptoms persist. Management should be aimed at symptom reduction and coping strate-
gies.

INTRODUCTION peripheral nerve distributions.5 The onset of BMS

is most often spontaneous and symptoms prog-
Burning mouth syndrome (BMS) is a chronic con- ress gradually in most patients, often persisting
dition characterized by a burning sensation of the for several years.8–10 Complete spontaneous reso-
intraoral mucosa in the absence of a local or sys- lution after 5 years has been reported in less than
temic cause.1–3 It is primarily a diagnosis of exclu- 3% of affected individuals, and less than 30% of
sion based on subjective symptoms.4–6 The patients with BMS show moderate symptom
International Classification of Headache Disor- improvement with or without treatment.9 The
ders, Third Edition (ICHD-3), stipulates that, for a cause and pathophysiology of BMS are not well
diagnosis of BMS, the burning sensation or dyses- understood, although various mechanisms have
thesia must recur daily for more than 2 h/d for been explored.4,5,11 There is no known cure for
more than 3 months, without any clinically evident BMS and management is aimed at symptom
causative lesions.7 The World Health Organization reduction. A variety of topical, systemic, and
adds that BMS is characterized by significant behavioral therapies have been used in the treat-
emotional distress or interference with orofacial ment of BMS with varied success.4,12–14
functions and lowers the symptom threshold to
recurring for 2 h/d on 50% of the days for more
than 3 months.2 EPIDEMIOLOGY
The characteristic burning sensation of BMS is BMS first appeared in the medical literature in the
typically bilateral and is most commonly experi- 1800s15 and has also been referred to as burning
enced on the tongue, although it can be experi- mouth, oral dysesthesia, stomatodynia, glossody-
enced anywhere in the intraoral mucosa, nia, and glossopyrosis.2,5,6 There has historically
including the lips, hard palate, gingiva, and buccal been significant heterogeneity in the definition of
mucosa.4,5,8 The sensation does not follow BMS used in the literature, with several studies

a
Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital, 1620 Tremont St, Suite 3-02B, Bos-
ton, MA 02120, USA; b Center for Integrative Oral Health Inc., 7151, University Boulevard, Unit 110, Winter
derm.theclinics.com

Park, FL 32792, USA; c University of North Carolina-Chapel Hill, Adams School of Dentistry, Campus
Box 7450, Chapel Hill, NC 27599-7450, USA; d University of North Carolina-Chapel Hill, Adams School of
Dentistry, Chapel Hill, NC 27599-7450, USA
* Corresponding author.
E-mail address: [email protected]

Dermatol Clin 38 (2020) 477–483

https://doi.org/10.1016/j.det.2020.05.008
0733-8635/20/Ó 2020 Elsevier Inc. All rights reserved.
478 Klein et al

including patients whose burning sensation is CLASSIFICATION

attributable to an underlying condition.2,3,12
Because of this, the estimated prevalence of BMS may be classified as primary or secondary.13
BMS varies widely, with reports ranging from In this model, primary BMS refers to a persistent
0.7% to 8% of the population.3,16 BMS has a burning sensation in the absence of clinical find-
strong female predilection, with women affected ings, and secondary BMS refers to a burning
up to 7 times more than men.8,10,13,16 Almost all sensation related to an identifiable underlying con-
patients with BMS are perimenopausal and post- dition. Consensus definitions have since moved
menopausal women, with symptoms presenting away from this model in favor of stricter criteria
between 3 years and 12 years following the onset in which burning sensation attributable to an un-
of menopause.3,4 The mean age at diagnosis is be- derlying condition is not considered BMS.2,7
tween 59 and 61 years, and BMS rarely occurs BMS can also be classified based on variations
before the age of 30 years.6,17 in pain intensity over a 24-hour period (Fig. 1). In

Fig. 1. Classification of BMS.

 Burning Mouth Syndrome 479

this model, type 1 BMS is characterized by differentiable without further testing. However,
symptom-free waking with burning sensation determining the underlying disorder in a given pa-
developing in the late morning, progressing tient may allow more targeted therapy.5,11
throughout the day, and peaking in intensity in
the evening. Type 2 BMS is the most common CLINICAL FEATURES
presentation and is characterized by continuous
burning throughout the day, which makes falling BMS has a varied clinical presentation. The char-
asleep difficult. In type 3 BMS, patients have acteristic burning sensation is typically bilateral
intermittent symptoms present only on some and is experienced most commonly on the tongue,
days.8,18,19 followed by the anterior hard palate and labial mu-
cosa.8,16,17 Patients may describe this burning as
CAUSE AND PATHOPHYSIOLOGY scalding, tingling, or numb.3,12,13 The reported in-
tensity of pain experienced varies widely, but
The cause of BMS is not well understood, but most patients describe their pain as mild or mod-
there is an emerging consensus that, for most pa- erate on 0 to 10 numerical pain scales as well as
tients, it is neuropathic.4,5,7,11,20,21 BMS may on subjective descriptions of mild, moderate, and
represent a convergent clinical presentation of severe pain.17 For some patients, the burning
dysfunction arising in the peripheral nervous sys- sensation is exacerbated by consuming hot foods
tem, central nervous system, or both.4,5 or drinks and relieved by cold.8,12,20 Xerostomia is
It has been proposed that most BMS cases a common complaint in patients with BMS.16
can be attributed to peripheral small fiber neu- Although there do not seem to be differences in
ropathy in the intraoral mucosal epithelium.5,20 stimulated saliva flow between patients with
Tongue biopsies performed in patients with BMS and controls, there is some evidence of
BMS have revealed a decreased density of small decreased unstimulated salivary flow and of
fiber nerve endings compared with controls, different salivary composition.26,27 However, these
consistent with a small fiber neuropathy, findings are controversial because hyposalivation
although these studies have been performed on represents an identifiable underlying cause, thus
a limited number of subjects and may not be precluding patients with this presentation from a
generalizable to all patients with BMS.5,22,23 Im- diagnosis of BMS.
munostaining of tongue biopsies has also Many patients with BMS experience taste dis-
revealed an increased expression of transient re- turbances, including persistent metallic or bitter
ceptor potential cation channel subfamily V taste and alterations in salty, sweet, or bitter
member 1 (TRPV1) channels.24 TRP channels tastes.8,11 There is some evidence that BMS and
play an important role in temperature perception, taste dysfunction are linked via hypofunction,
sensitization, and nociception, and an increased damage, or loss of inhibition to the chorda
number of TRPV1 receptors could contribute to a tympani, a branch of the facial nerve that caries
heightened pain sensation.4,5,11 taste sensation to the anterior two-thirds of the
Another subset of BMS may constitute a sub- tongue.11,28–30 Psychological and psychiatric fac-
clinical trigeminal neuropathy, a theory based on tors have been found to play a role in BMS, with
abnormalities of the masseter and blink reflexes, anxiety and depression being commonly observed
which are commonly evaluated when testing tri- comorbid conditions.31 Sleep disturbances are
geminal nerve function, observed in approximately also widely reported, including trouble falling
20% of patients with BMS.5 The remainder of pa- asleep, awakening during the night, and poor
tients may experience BMS as centrally mediated sleep quality.8,19,32
pain, possibly related to the hypofunction of dopa-
minergic neurons in the basal ganglia, which are DIFFERENTIAL DIAGNOSIS
involved in the inhibitory modulation of pain.25 Al-
terations in this system are similar to those BMS can be a debilitating, chronic condition, so it
observed in Parkinson disease, and there is is imperative that local and systemic causative
some evidence of an increased incidence of factors be ruled out. Local factors include paraf-
BMS in patients with Parkinson disease.5 unctional habits (eg, bruxism, tongue thrust) and
Decreased levels of dopamine in the basal ganglia poorly fitting dentures.3,4,6,33 Each of these can
of some patients with BMS may represent a com- produce microtrauma and local erythema that
mon disease pathway for BMS and depression, result in a burning sensation.33 Clinical findings
which are often comormid.5 Importantly, periph- indicate that parafunctional habits include waking
eral and central nervous system involvement are up with headaches, tenderness in the muscles of
not mutually exclusive, nor are they clinically mastication on palpation, and partner observation
480 Klein et al

of grinding at night.6 Candidiasis, a common oral there are clinical signs of a hypersensitivity reac-
fungal infection produced by Candida albicans, is tion, as well as fungal cultures if candidiasis is sus-
another common local cause of oral pected and empiric therapy fails. Biopsy is not
burning.3,4,12,33 Geographic tongue, lichen planus, indicated to confirm a diagnosis of BMS6 (Fig. 3).
and other oral mucosal diseases should be ruled
out via clinical examination.6,12 Local allergic reac- MANAGEMENT
tions, possibly to dental materials or to new tooth-
paste or mouthwashes, may also result in a A variety of topical, systemic, and behavioral ther-
burning sensation.6,33,34 Systemic factors that apies have been used, with mixed results, in the
can cause or exacerbate oral burning include treatment of BMS (Table 1). Clonazepam, a
medications, vitamin deficiencies, and systemic benzodiazepine that agonizes the inhibitory neuro-
disease. Various medications have been shown transmitter gamma-aminobutyric acid (GABA), has
to produce oral burning as a side effect, including been used both topically and systemically to
antihistamines and antihypertensives, especially manage BMS and has been shown to reduce
angiotensin-converting enzyme inhibitors, antiar- symptoms in both short-term and long-term
rhythmics, and benzodiazpenes.33 Several nutri- intervals.3,4,6,14,35,36 Side effects of clonazepam
tional deficiencies have been explored in BMS, include xerostomia, lethargy, and fatigue.35 Impor-
including vitamins B12, B6, D, iron, and zinc.33 In tantly, clonazepam can cause physiologic and
addition, gastroesophageal reflux, diabetes melli- psychological dependence, whether used system-
tus, and hypothyroidism are diseases that can all ically or topically.3 Patients should be made aware
cause oral burning4,12,33 (Fig. 2). of this risk and advised to take the medication as
Evaluation of a patient presenting with a prescribed and not to discontinue abruptly.
complaint of oral burning should begin with a thor- Capsaicin, a neuropeptide extracted from chili
ough history. The history of present illness, medi- peppers that binds to TRPV1, can be applied topi-
cations, allergies, medical history, a thorough cally to treat BMS through the proposed mecha-
review of systems, and recent dental procedures nism of reducing the number of TRPV1
should all be reviewed to identify factors that receptors, leading to long-term desensitization of
may cause oral burning as well as any comorbid pain receptors to heat.4,6,37,38 Although this
conditions. An extraoral examination (including method may cause increased burning immediately
gross cranial nerve assessment) and an intraoral following application, it has been shown to pro-
examination should be performed, noting any duce long-term symptom relief.14
changes in mucosal color, consistency, or texture. Alpha-lipoic acid (ALA), an antioxidant with a
The examination should also include an evaluation role in nerve repair, has been shown to improve
of the dentition, periodontium, and any removable BMS symptoms in some studies, but these results
prostheses. Additional diagnostic work-up may have been inconsistent and there has been
include laboratory studies, as indicated, to rule considerable heterogeneity among trials.3,6,14
out systemic conditions or nutritional deficiencies. There have been reports of increased heartburn,
Patch testing for allergens may also be helpful if gastrointestinal upset, and headaches with ALA.

Fig. 2. Factors associated with oral burning.

 Burning Mouth Syndrome 481

Fig. 3. Diagnostic work-up for BMS.

Although its use is less evidence based than some acceptance for pain relief. This acceptance is
alternatives, ALA is offered by some clinicians as a promising in the treatment of BMS because
first-line therapy, particularly for patients who wish SNRIs are associated with fewer anticholinergic
to avoid prescription medications.3 effects, including xerostomia, than TCAs.39 The
Gabapentin is an anticonvulsant that has been evidence on these medications in the treatment
successfully used to treat other neuropathic pain of BMS is limited, but, given the impact of BMS
conditions. It has been shown to reduce symp- on quality of life and mood, they may benefit pa-
toms in patients with BMS, especially when used tients when prescribed and managed by a quali-
in conjunction with ALA.4,6,14 fied practitioner.3
Antidepressants, including tricyclic antidepres- There is some evidence that cognitive behavior
sants (TCAs), selective serotonin reuptake inhibi- therapy (CBT) can be effective in managing pa-
tors, and serotonin-norepinephrine reuptake tients with BMS, particularly resistant BMS.3 In
inhibitors (SNRIs), have been explored as the context of BMS, CBT can help to reduce
possible therapeutic agents for BMS.3,4,6,14 Anti- pain catastrophizing and to improve mood and
depressants have long been used in the manage- coping strategies.3,4 Long-term symptom
ment of neuropathic pain conditions.39 TCAs, improvement has also been observed.4,14 Intraoral
such as amitriptyline and nortriptyline, have devices designed to mitigate parafunctional
been found to be most effective, but SNRIs, a tongue habits have also shown limited benefit in
newer class of antidepressant, are gaining BMS symptom management.40

Table 1
Pharmacotherapeutic interventions

Topical or
Category Medication Systemic Dose and Delivery
Benzodiazepine Clonazepam Topical 0.5 mg to 2 mg swish and expectorate or
tablet held in mouth and expectorated
Systemic 0.5 mg capsule or orally disintegrating
tablet starting dose taken at bedtime,
not to exceed 2mg/d
Tricyclic Amitriptyline Systemic 10–25-mg starting dose taken at bedtime,
antidepressant titrated to maximum dose of 100–125 mg
Anticonvulsant Gabapentin Systemic 300 mg/d at bedtime starting dose,
up to 900–1200 mg 3 times daily
Atypical analgesic Capsaicin Topical 0.2% solution (can dilute TabascoÔ sauce)
swish and expectorate 4 times daily
Supplement Alpha-lipoic acid Systemic 200 mg 3 times daily
482 Klein et al

Recent meta-analyses and systematic reviews DISCLOSURE

of BMS therapies have cautioned that there is a
paucity of high-quality research and a high risk of The authors have nothing to disclose.
bias in most of the available studies. Further
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