Halitosis

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Halitosis

Jaisri R. Thoppay, Andreas Filippi, Katharine Ciarrocca,


John Greenman, and Scott S. De Rossi

Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Local Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Systemic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Psychogenic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Clinical Pathologic Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Patient Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

J.R. Thoppay (*)


Oral Medicine, Orofacial Pain and Geriatric Programs,
Orofacial Pain and Geriatric Oral Health Programs,
Department of Oral and Maxillofacial Surgery, VCU
School of Dentistry and VCU Medical Center, Virginia
Commonwealth University, Richmond, VA, USA
e-mail: jthoppay@vcu.edu
A. Filippi
Department for Oral Surgery, Oral Radiology and Oral
Medicine and Center of Salivary Diagnostics and
Hyposalivation, University Center for Dental Medicine
Basel, University of Basel, Basel, Switzerland
e-mail: andreas.filippi@unibas.ch
K. Ciarrocca
Dental College of Georgia, Augusta University, Augusta,
GA, USA
e-mail: kciarrocca@augusta.edu
J. Greenman
Faculty of Health and Life Sciences, Bristol, UK
e-mail: John.Greenman@uwe.ac.uk
S.S. De Rossi
UNC School of Dentistry, Chapel Hill, NC, USA
e-mail: scott_derossi@unc.edu

# Springer International Publishing AG 2018 1


C.S. Farah et al. (eds.), Contemporary Oral Medicine,
https://doi.org/10.1007/978-3-319-28100-1_27-1
2 J.R. Thoppay et al.

History and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17


Clinical Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Diagnostic Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Conclusions and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Abstract 2014). Patients with halitosis often present to


Halitosis, commonly known as bad breath, is either a dentist or a primary care medical doctor.
an unpleasant symptom that can present as a Halitosis is broadly classified into genuine
social problem compromising quality of life. halitosis, pseudo-halitosis, and halitophobia
This condition may affect individuals of all (Miyazaki et al. 1995) and as either intra-oral or
ages and may be a transient episode or a long- extra-oral (Tangerman and Winkel 2010).
lasting problem depending on the cause. In Although these classifications are widely used,
some cases, patients may present with neither are universally accepted as classification
pseudo-halitosis, whereby there is a belief and criteria for genuine halitosis. Also this
that they have bad breath despite their malodor does not appropriately differentiate genuine
not being perceived or detected, either by those halitosis from underlying pseudo-halitosis and
around them or by objective analysis. Halitosis halitophobia. Many authors have used pseudo-
can occur due to local factors, or in rare cases halitosis, halitophobia, or delusional halitosis
be attributed to systemic etiologies. For synonymously (Murata et al. 2002); however,
patients who present with halitosis exclusively these are not synonymous. A perceived pseudo-
from local oral factors, improving oral health presentation occurs in the absence of any identifi-
including tongue cleaning, treating dry mouth able cause or presence of objectively significant
and alleviating local causes, may be beneficial. malodor and is often referred to as pseudo-
For patients with a systemic etiology for their halitosis providing that the patient realizes (when
halitosis, a multidisciplinary management faced with objective feedback) that they do not
approach may be necessary. actually have bad breath (Brunner et al. 2010).
Halitophobia, on the other hand, delineates indi-
Keywords viduals who stubbornly refuse to accept objective
Bad breath  Oral malodor  Halitosis  Pseudo- evidence which rules out an identifiable cause and
halitosis  Breath disorders cannot be convinced that their breath is anything
but malodorous (Seemann et al. 2014; Aydin and
Harvey-Woodworth 2014). Halitophobia may
often synonymously be used as delusional halito-
Introduction sis by clinicians; however, delusional halitosis is a
monosymptomatic hypochondriasis, or otherwise
The potential emanation of malodor from breath is an imaginary halitosis, and is a manifestation of
called halitosis, which is derived from the Latin olfactory reference syndrome. Halitophobia refers
word halitus meaning “breath” or halare “to to patients who often dislike or worry about hav-
breath” with a suffix from the Greek based noun ing bad breadth (Hayashi et al. 2010; Bollen and
-osis (Douglas Harper 2016). Although many Beikler 2012).
descriptions of this terminology are available, Genuine halitosis may be physiological or
they are inadequate in precisely defining the var- pathological with both the subjective complaint
ious presentation of this condition (Porter and and objective detection and measurement by
Fedele 2014; Aydin and Harvey-Woodworth organoleptic evaluations or analytic instruments.
Halitosis 3

Fig. 1 Multifactorial
relationship in etiology of
halitosis
Local factors-Oral
cause
Saliva, pH, Plaque calculus, periodontal disease,
Dental caries, food impaction etc.,

Volatile sulfur
compounds

Psychogenic factors Systemic factors


Extra-oral cause Extra-oral cause
Underlying psychiatric disease, stress, anxiety etc., Underlying systemic disease

Typically, genuine halitosis is multifactorial as odors. Further, the presence of halitosis may be
illustrated in Fig. 1. It can potentially present self-reported by the patient or brought to discus-
with any combination of local and/or systemic sion by a spouse or acquaintances. Halitosis is
conditions reflecting the multifactorial nature of often socially difficult to discuss or accept since
the complaint. Accurate understanding of halito- it is impossible for anyone to smell their own
sis is essential for efficient and appropriate clinical breath. Therefore, it often relies on others around
management of the complaint (Tangerman 2002; the individual to highlight the problem. This is
Bolepalli et al. 2015). further complicated by social stigma and the
reluctance of those around the individual with
bad breath to inform them of the issue. Indeed
Epidemiology any dialogue about oral malodor may not always
be a pleasant point of discussion. Sometimes peo-
Halitosis is a common condition that is present in ple who interact with the individual with bad
50–65% of the world’s population (Mokeem breath may not openly discuss the issue; rather
2014). A Dutch survey agency has reported that they may display a gesture of repulsion as they
halitosis is one of the top 100 human social vex- experience bad breath. This may prompt the indi-
ations based on a public investigation in the Neth- vidual’s awareness of halitosis. When halitosis is
erlands in 2005 (Bollen and Beikler 2012). transient, it is often not reported and hence further
Despite this condition being a significant source complicates epidemiological studies.
of exasperation, a precise estimate of prevalence Halitosis is a problem of all centuries, occur-
is not possible as epidemiological studies are lim- ring universally in both genders and affecting
ited (Bollen and Beikler 2012). There are several patients of all ages with varying prevalence
reasons for the lack of scientific data about hali- rates. Oral malodor has been recognized in the
tosis. There is the absence of standardized literature from ancient times (Fischman 1997).
approaches in evaluation methods as well as the Descriptive epidemiological studies show that
difference in cultural and racial appreciation of moderate chronic halitosis affects approximately
4 J.R. Thoppay et al.

one-third of the population, whereas severe hali- and methionine) drips onto the tongue surface and
tosis may involve less than 5% of the population soaks into the biofilm matrix and is then trans-
(Rosing and Loesche 2011). The correlation formed into VOC and VSC by microbial enzymes.
between age and malodor indicates an increasing For morning breath and hyposalivation, the nutrient
intensity of odor in older adults. Though age is not substrate supply rate to the biofilm microorganisms
strictly a risk factor for malodor, comorbidities (i.e., salivary flow) is severely limited. This
such as increased incidence of periodontal disease increases the residence time of the fluid phase
in association with tongue coating are reported within the tongue biofilm matrix, since there is no
as key factors that aggravate oral malodor in the flushing action or dilution from salivary flow.
elderly population (Miyazaki et al. 1995). Increasing the residence time provides a longer
About 80–90% of halitosis cases are thought to enzyme-substrate interaction time, and more micro-
be due to high local concentrations of intra-oral bial transformations which proceed to completion,
microbial populations particularly those of tongue especially hydrolysis of salivary mucin (glycopro-
biofilms (cells within a salivary domain) and also teins) – the main source of organic nutrients, which
the biofilms associated with teeth and periodontal proceeds in a two-stage process. Glycohydrolases
tissues. Main causes include gingival and peri- (enzymes responsible for deglycosylation) first
odontal pathologies, tongue coating, caries, or remove the sugar moieties leaving a peptide back-
poor oral hygiene. In comparison to the tongue, bone or core, which is then attacked by microbial
the gingival crevice serves as a host-tissue-serum proteases and finally digested into amino acids or
domain, especially in cases of gingival patholo- small peptides (i.e., cell membrane transportable
gies, dental caries, and poor oral hygiene. Extra- small molecules) allowing the microbes to trans-
oral causes of halitosis contribute to about form these substrates into products (including VOC
10–20% of all cases and are caused by poor diet, and VSC). Hence, the first step (deglycosylation of
alcohol abuse, tobacco smoking, certain drugs, salivary glycoproteins) may be an important step in
and diseases of other parts of the digestive tract oral malodor production. Salivary mucins are a
as well as some systemic conditions (Zalewska common source of proteins causing malodor.
et al. 2012; Tangerman and Winkel 2010). More- Trapped epithelial cell components also consist of
over, it is entirely feasible that both intra-oral and various glycoproteins. Glycoprotein degradation
extra-oral conditions may both contribute to total commences with the detachment of the various
bad breath levels simultaneously. glyco-sugars from the protein core, and glycosylhy-
drolases are commonly found in Gram-positive
bacterial species. The exposed protein core is then
Etiology unprotected against the activities of various types of
proteases and peptidases, particularly those pro-
Intra-oral chronic malodor is primarily a condition duced by anaerobic Gram-negative species, under
of the tongue surface whereby microbial biofilms anaerobic conditions. Figure 2 summarizes the eti-
(which form within tongue crypts, fissures, and ology of halitosis.
papillae) generate odiferous volatile organic com-
pounds (VOCs), some of which (e.g., the volatile
sulfur compounds [VSC]) partition into the Local Factors
gas phase headspace above the tongue (i.e., oral
cavity). Even in periodontal disease, the tongue Oral malodor results from conditions such
surface is thought to contribute more than as periodontal disease, inadequate saliva flow,
the periodontal crevice to a malodor, due to its inadequate or failed dental restorations, tongue-
much larger surface area (at the microscale) than coating accumulation, or unclean dentures. The
the teeth and gingiva. Also in periodontal disease, a decomposition of organic substrates by oral anaer-
higher flow rate of the gingival crevicular fluid obic bacteria produces VOC, and in particular
(which is rich in VSC substrates like cysteine VSCs that lead to halitosis.
Halitosis 5

Fig. 2 Etiology of halitosis


Etiology of halitosis

Physiological Pathological
[Generally transient]

Local Systemic

Medication
Local Systemic and Substance Psychogenic
induced

Physiological Pathological
In general, local causes of halitosis can be physi- Oral malodor predominantly caused by local path-
ological which can be transient due to the circa- ologic factors are periodontal disease (Fig. 3),
dian rhythm in human salivary flow that naturally poor or low salivary flow, failed dental restora-
diminishes during sleep, or due to the certain tions such as fractured crown and bridges or
characteristic odor of food substances. This type class II restorations with loss of contact or failed
of malodor is attributable to putrefaction of restoration margins (Fig. 4), coated tongue and/or
retained oral epithelial cells and food debris caus- glossitis, food impaction between teeth, hairy
ing an unpleasant odor, which disappears when tongue, fissured tongue, fungal infections, oral
normal salivary flow resumes or food debris squamous cell carcinoma, or unclean dentures.
are cleared (Rosing and Loesche 2011). Other Extensive studies on halitosis have predominantly
physiologic causes may be hormonal, such as focused on periodontal disease and tongue biofilm
conditions reported during menstruation, which coating (Fig. 5) as primary contributing elements
may be due to high VSCs. The pH of saliva of halitosis in the oral cavity. This may be due
and salivary levels of Prevotella intermedia in to the high prevalence of these conditions, and
subjects with preexisting periodontitis were sig- periodontal disease–associated bacteria (even if
nificantly higher in the ovulation phase than in the displaced onto the tongue as a transient colonizer)
follicular phase. A change in salivary pH and are capable of producing significant amounts
changes in VSC and P. intermedia during the of VSCs. Decomposition of organic substances
menstrual cycles of women with periodontitis by oral anaerobic bacteria produces VSCs leading
seems to correlate to the level of oral malodor to halitosis (Tonzetich 1978).
(Kawamoto et al. 2010). Further, during men-
strual phases, it was noted that the salivary anti-
oxidant capacity decreased, while bleeding on Systemic Factors
probing and P. intermedia counts increased, over
the course of the menstrual cycle in women with Extra-oral or non-oral factors can cause halitosis.
periodontitis. Antioxidant capacity could be Extra-oral halitosis has origins outside the mouth.
involved in the pathogenesis of periodontitis It has been reported to arise from certain systemic
(Kawamoto et al. 2012). However, the associa- diseases such as acute febrile illness, chronic
tions are not well studied or clearly explained and sinusitis, or post nasal drip. Also metabolic disor-
there is limited evidence in the literature. ders such as diabetic ketoacidosis may cause
6 J.R. Thoppay et al.

Fig. 3 (a) and (b) Plaque accumulation (white arrows) and gingival bleeding (black arrow)

Fig. 4 Fractured dental


restorations. Class II
restoration (a), and portion
of gold crown (b)

malodor. Consumption of medications and certain odor, the details of specific odors and their etiol-
foods may result in characteristic malodor that ogy are illustrated in Table 1 (Tangerman and
may be specific to the medication or food respec- Winkel 2010; Tangerman et al. 2012; Tangerman
tively. Extra-oral halitosis can be divided into 2002; Tangerman and Winkel 2007; Ferguson
two groups: blood-borne and non-blood-borne et al. 2014).
halitosis. The conditions and its specific odorant, In extra-oral blood-borne halitosis, volatile
for example, dimethyl sulfide producing pungent odorous compounds are produced as a result of
odor and hydrogen sulfide producing a rotten egg various metabolic processes. Odorous volatile
Halitosis 7

Fig. 5 (a) Tongue coating in areas of hyperplastic papilla (arrow) in contrast with other areas. (b) Tongue coating with
yellow hue due to food colorants

sulfur compounds also cause most of the reported nasal origin than from oral areas (Tangerman and
cases of blood-borne halitosis. In extra-oral Winkel 2010).
blood-borne halitosis, VOC that are produced in
the body that result from metabolic processes are Medication and Substance-Induced
taken by the blood stream and are transported to Halitosis caused by medications, food, or other
the lungs and result in exchange of gases resulting substances can be due to exogenous or endoge-
in exhalation of VOC in exhaled air. Breath anal- nous processes. The exogenous process is tran-
ysis of exhaled air with VOC has shown correla- sient. Oral odor can be affected by intake of food
tion to the underlying metabolic condition. For such as garlic, certain spices, and drinks such as
example, a high level of dimethyl sulfide (DMS) coffee. Such presentations may be transient.
content in breath and venous blood was observed Endogenous processes of halitosis either
in cirrhotic liver disease. However, the nature of (a) predispose or promote bacterial activity lead-
the compounds differs from that of the volatiles ing to putrefaction causing malodor or (b) reduce
found in halitosis of oral origin in contrast to the or modify the salivary flow (Madhushankari et al.
extra-oral etiologic agents causing halitosis 2015). Certain foods or substances are capable
(Tangerman and Winkel 2010; Tangerman et al. of altering the oral environment such as oral dry-
2012; Tangerman 2002; Tangerman and Winkel ness or by providing a source of high concentra-
2007; Erovic Ademovski et al. 2012; Katsinelos tion of protein or sugar. Furthermore, dairy
et al. 2007). products are known to break down in the mouth,
Non-blood borne halitosis may result from leading to the release of amino acids that are rich
predominantly upper respiratory tract infections in sulfur. Both onion and garlic also contain high
including the nose and occasionally from the concentrations of sulfur compounds (e.g., allyl-
lower respiratory tract as reported in several case methyl sulfide), which can pass through the lining
studies. Such patients may have bad breath from of the intestine into the bloodstream and
8 J.R. Thoppay et al.

Table 1 Systemic causes and characteristic odorants


System/
condition Condition Malodorant Odor nature
General Acute febrile illness Dimethyl Pungent, rotten
Pyrexia sulfide cabbage
ENT Chronic sinusitis Hydrogen Rotten eggs
Upper respiratory tract infection sulfide
Postnasal drip Methyl Pungent, rotten
Nasal foreign bodies mercaptan cabbage
Malignancy Musty odor
Esophageal Pharyngo-esophageal diverticulum, gastro-esophageal Hydrogen Rotten eggs
reflux disease sulfide
Zenker’s diverticle Methyl Pungent, rotten
mercaptan cabbage
Gastrointestinal Pyloric stenosis Dimethyl Unpleasantly
duodenal obstruction sulfide sweet
inflammatory bowel disease n-Butyric acid Rancid
Constipation, obstruction Skatole Fecal like
Metabolic Metabolic syndrome Dimethyl Unpleasantly
sulfide sweet
Diabetic ketoacidosis Acetone Fruity
Fish odor syndrome Trimethylamine Fishy
Renal Renal failure Ammonia Pleasantly sweet
Uremia Dimethyl Fishy
amine
Trimethylamine Fishy
Hormonal Menstruation Dimethyl Unpleasantly
sulfide sweet
Hepatic Hepatic failure Dimethyl Unpleasantly
sulfide sweet
Hematologic Leukemia Dimethyl Unpleasantly
sulfide sweet
Hydrogen Rotten eggs
sulfide
Methy Pungent, rotten
mercaptan cabbage

subsequently be released into the lungs and then mouth and lungs but also further aggravates the
exhaled. situation because of its drying effect on the oral
Halitosis can also be caused by side effects mucosa (Aydin and Harvey-Woodworth 2014;
from medications or by odor from substances Zalewska et al. 2012; Porter 2011).
such as alcohol, tobacco, or betel. Smoking or Malodor can result as a side effect from med-
chewing tobacco products and alcohol consump- ications. For example, nitrates prescribed to
tion may cause long-standing halitosis by drying treat angina or hypertension can cause malodor;
the oral mucosa (Porter 2011). Nicotine stains however, stopping the medication may not be
may be strongly adherent to oral hard and soft reasonable (Madhushankari et al. 2015). Drugs
tissues (Fig. 6), and hence nicotine-induced hali- such as lithium salts, griseofulvin, dimethyl sulf-
tosis may be persistent even after cessation of oxide, antihistaminic, phenothiazine derivatives,
nicotine use. Cigarette smoking not only raises chloral hydrate, amphetamines, suplatasilate, met-
the concentration of volatile compounds in the ronidazole, penicillamine, thiocarbamide, ethyl
Halitosis 9

subjective health, economic status, and stress


levels have been associated with halitosis.
Stressed or anxious individuals typically more
easily perceive halitosis compared to stress-free
individuals (Alzoubi et al. 2015). Psychopatho-
logical problems have been proposed to either
induce or aggravate halitosis (Nosratzehi et al.
2017). The prompt may originate from awareness
to the problem because of personal sensitivity or
brought to notice by surrounding people or both
(Eli et al. 1996). Individuals with genuine halito-
sis may feel some emotional changes, regardless
of the actual degree of halitosis (Suzuki et al.
2008). Not only patients with pseudo-halitosis
but also those with genuine halitosis may have
an accompanying psychological condition. A
Fig. 6 Nicotine staining of dentition (arrows)
questionnaire can be used to evaluate the psycho-
logical condition of a patient with reported halito-
alcohol, diuretics, benzodiazepines, nitrites and sis. Psychologists and Psychiatrists frequently use
nitrates, bisphosphonates, arsenic salts, disulfi- established questionnaires to diagnose underlying
ram, and cytotoxic agents can also cause halitosis psychiatric problems; however, when halitosis is
(Table 2). These medications have a tendency to the primary complaint with a possible psychiatric
cause dry mouth and occasionally salivary gland factor, then the psychological questionnaires can-
hypofunction, lowering oral pH which facilitates not be recommended for use at the initial visit,
production of VSCs. Some medications such as because their use may cause a patient to believe
oral contraceptives can also aggravate periodontal that the clinician suspects a psychosomatic condi-
disease (Heasman and Hughes 2014), as can anti- tion. As stated previously, the etiology of halitosis
hypertensive medications causing gingival hyper- is typically multifactorial, and hence an individual
plasia, which increases the prevalence of may in fact have genuine halitosis complicated by
periodontal disease by increasing sulfide and psychogenic factors. Contrarily, patients with
nitrate producing bacteria resulting in oral mal- pseudo-halitosis and halitophobia believe that
odor (Porter and Fedele 2014; Bollen and Beikler they have oral malodor, even in the absence of
2012; Aylikci and Colak 2013; Porter and Scully any offensive halitosis (Eli et al. 1996). Further,
2006). in almost all cases of delusional halitosis, there is
usually an underlying psychosomatic problem,
which can range from an overvalued belief to a
Psychogenic Factors frank delusional disorder. Sometimes the delu-
sion may be so firm that the individual can hardly
Halitosis is a symptom related to both somatic be dissuaded from their belief of mouth odor
and emotional status. When the subjective and (Hayashi et al. 2010; Akpata et al. 2009).
objective factors of oral malodor that initiate the Patients with delusional halitosis perceive other
complaints of oral malodor do not have evident people’s behavior such as covering of the nose or
clinical correlation to any organic pathology, that averting the face as an indication that their breath
raises the possibility of psychological aspects is offensive. This makes then believe that they
involved with a complaint of halitosis (Eli et al. have offensive odor and seek care (Akpata et al.
1996). Several psychosocial factors such as 2009).
10 J.R. Thoppay et al.

Table 2 Medication induced halitosis


Medications that cause malodor
• Chloral hydrate
• Nitrites and nitrates
• Dimethyl sulphoxide
• Disulphiram
• Some cytotoxic agents
• Phenothiazines
• Amphetamines
• Triamterene
• Lithium salts
• Arsenic salts
• Paraldehyde
• Thicarbamide
• Penicillamine
• Metranidazole
• Bisphoshonates
• Ethylalcohol
• Griseofulvin
Medications that may cause oral dryness that may secondarily cause halitosis due to salivary changes:
• Antihistamines
• Tricyclic antidepressants
• Anti epileptic/antiparkinsonism medications
• Diuretics
• Antihypertensive
• Anxiolytics and antipsychotics
• Anorexiant
• Anticholinergics/antispasmodics
• Muscle relaxants
• Narcotics
• Sedatives

has a high potential to form a bacterial biofilm


Clinical Pathologic Features coating which constitutes a relatively large bacte-
rial population (Fig. 11). The biofilm “matrix” can
Pathophysiology house or trap epithelial cell debris, blood cells,
precipitated saliva proteins, and food debris as
Local Factors well as many species of oral bacteria that metab-
Halitosis originating in the oral cavity is most olize these substrates to produce VSCs (Amou
frequently associated with poor oral hygiene, a et al. 2014; Bolepalli et al. 2015; Ren et al. 2016).
heavy bacterial load of biofilms on tongue coat- Oral flora microorganisms potentially respon-
ing, dental plaque (Fig. 3), dental caries, gingivi- sible for halitosis are Streptococcus salivarius,
tis, oral mucositis (Fig. 7), periodontitis (Fig. 8), a Lysobacter-type species, Veillonella dispar,
fissured tongue (Fig. 9), hairy tongue or oral car- Actinomyces odontolyticus, Atopobium parvulum
cinoma (Fig. 10). Dental plaque, periodontal and Veillonella atypica, Bacillus subtilus,
pockets or pockets around dental implants, and Proteus vulgaris, Pseudomonas aeruginosa,
tongue coating are important sources of malodor. coliforms, Bacteroides melanogenicus, Clostrid-
However, the dorsoposterior surface of the tongue ium sporogenes, C. histolyticum, Treponema
is the most significant site that emanates odor. denticola, Porphyromonas gingivalis,
This is best explained by the tongue having the Porphyromonas endodontalis, Prevotella
largest surface area in the mouth with pits, fis- intermedia, Bacteroides loescheii, Enterobac-
sures, and papillary structures. Subsequently, it teriaceae, Tannerella forsythensis, Centipeda
Halitosis 11

Fig. 9 Fissured dorsal tongue


Fig. 7 Oral mucositis with erythema and ulceration (white
arrow) and gingival desquamation (black arrow)

Fig. 10 Oral squamous cell carcinoma of gingiva and


buccal vestibule

et al. 2015; Awano et al. 2002). They have been


Fig. 8 Periodontitis with gingival recession exposing the associated with proteolytic activity in the oral
root surface (white arrow) and gingival erythema (black cavity. Deglycosylation of salivary glycoproteins
arrows) is an initial step in oral malodor production.
Salivary mucins are the most common source of
periodontii, Eikenella corrodens, Fusobacterium proteins causing malodor. Epithelial cell compo-
nucleatum, and other unidentified oral bacteria nents contain various glycoproteins. Glycoprotein
(Burton et al. 2006; Kamaraj et al. 2011; Grover lysis starts with the detachment of the protein
12 J.R. Thoppay et al.

rate, are the main causes for higher oral malodor


production (De Boever et al. 1994). A positive
correlation has been demonstrated between
severity of periodontitis and VSC levels in sub-
jects with periodontal disease who suffer from
oral malodor. Further, higher oral pH than neu-
tral physiologic pH favors the process of putre-
faction and volatilization (Grover et al. 2015).
There is a clear relationship between strength of
odor and increase of pH in biofilm matrix into
the alkaline phase (pH 6.7–pH 8.2). A maximum
rate of generation for hydrogen sulfide (H2S) is
pH 6.5–7.5, while for methyl mercaptan it is
nearer to pH 8.2. Carcinomas of the buccal
mucosa, floor of mouth, gingiva, tongue, and
palate typically ulcerate and necrotize even
when these lesions are small; thus, oral malodor
associated with oral cancer is characteristically
stronger because they are usually secondarily
infected.

Fig. 11 Coated bacterial slough on palatal mucosa (black


Systemic Factors
arrow), while lips and tongue show evidence of dryness While oral factors are localized phenomena, extra-
(white arrows) oral halitosis occurs when volatile substances
are absorbed within the body, such as the stomach,
from the carbohydrate portion. Gram-positive intestines, liver, and transferred into the blood-
bacterial activity is necessary for processing of stream that is later exchanged in pulmonary alve-
the protein core leading to glycoprotein lysis, oli and exhaled with breath causing malodor
which is then further degraded by Gram-negative (Tangerman and Winkel 2010). Nasal infections
microorganisms under anaerobic conditions. Pro- are the most common cause of extra-oral halitosis.
teolysis and amino acid utilization of the protein Such patients have bad breath from the nose
core are generally produced by Gram-negative instead of the mouth. This form is probably
bacteria (Grover et al. 2015; Sterer and Rosenberg more common in very young children who often
2002). insert foreign bodies into their nostrils, which
The putrefactive action of these microorgan- might lead to an offensive odor from the nose
isms on endogenous and exogenous proteina- (Tangerman and Winkel 2007). Children with
ceous substrates, including saliva, exfoliated mouth breathing habits may have changes in oral
cells, blood, food debris, and leukocytes are pri- microbial flora and excessive oral dryness causing
marily responsible for the production of methyl changes in quality and quantity of oral and oro-
mercaptan and hydrogen sulfide which are VSCs pharyngeal secretions resulting in tonsillar infec-
causing malodor. Also methylamine, dimethyl- tions and tonsilloliths (Fig. 12) which can also
amine, propionic acid, butyric acid, indole, katole, contribute to malodor (Motta et al. 2011). Ele-
and cadaverine have been reported to contribute to vated H2S levels may be due to erosive changes
oral malodor (Goldberg et al. 1994). The severity in infected tissue, and elevated methyl mercaptan
of periodontal disease, an increase in the amount (CH3SH) levels may be attributable to changes in
of tongue coating, and proteolytic “Benzoyl-DL- oral microbiota activity caused by slight changes
arginine-naphthylamide, [BANA] positive” bac- in pH values (Porter and Scully 2006; Rio et al.
teria, in addition to a reduction in salivary flow 2008).
Halitosis 13

Fig. 12 Tonsilloliths noted clinically in palatine tonsils Farah, Perth Oral Medicine & Dental Sleep Centre, Perth
(a) and overlying the left mandibular ramus on an ortho- WA, Australia)
pantomogram (b) (Image b courtesy of Professor Camile

VSCs are absorbed by the blood and trans- wall into the blood and then via the lungs into
ported to the lungs where there is an exchange in the breath as alveolar components (Zaric et al.
exhaled air due to a partitioning of the volatiles 2015). Interestingly, very little of the VSCs appear
between blood and air in the alveoli. While oral to reach the bloodstream or breath from microor-
malodor is largely caused by hydrogen sulfide ganisms within the small and large intestines to
[H2S] and methyl mercaptan [CH3SH] and to a produce VSC in humans. One possible explana-
lesser extent by dimethyl sulfide [(CH3)2S]; how- tion could be that the presence of VSCs in the
ever, only the latter compound may be detected in stomach may be due to swallowing of VSCs in
blood-borne halitosis (Murata et al. 2002; saliva thereby transferring VSC-producing bacte-
Tangerman 2002). Both H2S and CH3SH contain ria from the mouth into the stomach. This does not
a free -SH group, which immediately reacts with explain the resolution of halitosis through eradi-
blood within seconds, resulting in irreversible cation of H. pylori by antibiotics in some studies
binding and oxidation. This interaction prevents which infers a causal relationship between
transportation of methyl mercaptan and hydrogen H. pylori infection and halitosis (Werdmuller
sulfide from the blood into the alveolar air and et al. 2000; Zaric et al. 2015; Kappler and Schafer
thus into the breath. Dimethyl sulfide, however, is 2014; Katsinelos et al. 2007). On the contrary, one
a neutral molecule which is stable in blood and study has debunked the causal relationship
hence can be transported from the blood into the between H. pylori and halitosis; rather providing
alveolar air which results in elimination by exha- an alternative theory that eradication of H. pylori
lation. Because of the neutral nature of such sul- in the stomach may perhaps also eradicate part of
fide compounds, they are very stable in blood, and the normal VSC-producing bacteria in the mouth,
hence it becomes difficult to separate or remove thereby diminishing halitosis (Tangerman et al.
from breath (Tangerman and Winkel 2010). 2012).
Malodors from the stomach are reported to be Dimethyl sulfide has been reported as the main
caused by H. pylori, which results in high VSCs. volatile substance in hepatic dysfunction. Pre-
The odor is unable to escape from the stomach dominantly in end-stage hepatic failure, it has a
except during burping, belching, or vomiting as it characteristic odor called fetor hepaticus. This is
is trapped by the esophageal sphincter. It is pos- said to have the smell of fresh-cut hay. On the
tulated that VSCs formed by H. pylori in the other hand, renal failure may cause a uremic
stomach are transported through the stomach breath odor that may lessen with treatment of the
14 J.R. Thoppay et al.

Table 3 Characteristic presentations of malodorants


Substance/food/medication Malodorant Odor
Garlic Allyl methyl sulfide Garlic-like
Onion Methyl propyl sulfide Onion-like
Disulfuram Carbon disulfide Slightly pungent
Dimethyl sulfoxide Dimethyl sulfide Unpleasantly sweet
Cysteamine Dimethyl sulfide Unpleasantly sweet

underlying renal disease which is due to retention urine emanates a distinctive boiled cabbage smell
of nitrates and uremic compounds in the body (Khan and Shagufta 2014; Porter 2011).
(Han et al. 2014; Tangerman 2002).
A rare condition called trimethylaminuria, also Medication and Substance-Induced
known as fish odor syndrome, gives rise to When medications and substances are metabo-
longstanding oral and body malodor due to an lized, VSCs are formed as byproducts which
excess amount of trimethylamine in the body may cause malodor. Depending on the type and
(Khan and Shagufta 2014). This disorder reflects site of VSC formation, this may cause oral or
defective flavin mono-oxygenase (FMO) activity extra-oral halitosis. Characteristic presentations
which is often genetically determined by the pres- of malodorants are presented in Table 3. Oral
ence of several single nucleotide polymorphisms halitosis from food products is mostly caused by
of the FMO3 gene (D’Angelo et al. 2014). The food impaction in the oral cavity or is directly
presence of FMO3 results in an enzyme with related to the characteristic smell of the particular
decreased or abolished functional activity for tri- food product. Malodor caused by food impaction
methylamine N-oxygenation, thus leading to tri- is predominantly due to putrefaction by bacterial
methylaminuria. Occasionally an overload of activity resulting in VSCs causing malodor. Food
precursors of FMO, for example, following cho- products such as onion and dairy products have
line therapy for Huntington’s chorea or a unique flavor and smell that may cause malodor.
Alzheimer’s disease may also cause tri- Such products may cause transient malodor.
methylaminuria. It should be noted that the orig- These foods contain volatile organic compounds
inal generation of trimethylamine (which is that give a characteristic taste and smell. These
oxidized by FMO) is from bacteria in the colon compounds when putrefied by bacterial activity in
where they produce trimethylamine that is then the oral cavity or metabolized systemically result
absorbed into the bloodstream from the intestine. in volatile dienal or sulfuric compounds and lead
It should also be noted that some trimethylamine to malodor. For example, volatile compounds
(along with other organic amines, including such as -(E,E)-2,4-heptadienal smell like stale
putrescine and cadaverine) can also be generated peanuts; (E,Z)-2,6-nonadienal has a cucumber-
by the microbial tongue flora within the oral cav- like odor; (E,E)-2,4-decadienal is fatty or rancid-
ity and detected on breath. However, this is at smelling; 3-(methylthio)propanal has an odor like
relatively low levels compared to levels found in baked potatoes or soy sauce; and dimethyl trisul-
trimethylaminuria. Hypermethioninaemia may fide smells distinctly like cooked cabbage. Onion
also give rise to oral malodor which is an excess and garlic are common food products that are
of methionine protein in the blood. This condition known for their characteristic odor. While onion
can occur when methionine is not metabolized. and garlic can leave their sulfuric odor in the oral
Individuals with hypermethioninemia may exhibit cavity, they can also be absorbed into the blood-
intellectual disability and neurological problems stream, enabling a secondary source of odor that is
with deficits in motor skills (standing or walking), blood borne and exhaled in the breath. Most peo-
sluggishness, muscle weakness, and liver disease ple view the smell of fish as an unpleasant odor. It
(Oliveira et al. 2015). Also their breath, sweat, or is equated with a rotting malodor. Food with high
Halitosis 15

protein content, when deposited in the oral cavity, levels of VSCs (Fukui et al. 2010). Of interest,
has high affinity to odor causing bacteria whose during premenstrual syndrome, stress can
interaction under favorable circumstances causes increase VSCs without a decrease in salivary
VSCs resulting in malodor. For example, all types flow (Kawamoto et al. 2010). It is postulated that
of milk from whole milk to fat-free milk contain hormonal changes affect oral bacterial
the milk protein casein or its hydrolysis compo- populations via diminished tongue and mucous
nents (amino acids), which in the process of putre- cell desquamation rates and/or weaken the host
faction are biotransformed into VOC and VSC. immune system through changes in salivary IgA
Consumption of fermented milk products concentration. These changes may contribute to
containing live microorganisms with probiotic an increase in oral VSCs, even in the presence of
activity by Lactobacillus species has beneficial normal salivary flow (Zalewska et al. 2012). How-
effects on the body (Baltova and Dimitrov ever, another study showed that concentrations of
2014). By improving the balance of intestinal IgA and chromogranin A in saliva were not sig-
microflora and action against microbes which are nificantly different among the groups studied, but
responsible for the production of VSCs are limited there were higher salivary cortisol concentrations
(Iwamoto et al. 2010). Also unfavorable condi- in subjects with high stress indicators as per the
tions such as low oral pH may decrease the ben- Cornell Medical Index (CMI) Health Question-
eficial effects (Porter 2011; Burton et al. 2006; naire (Fukui et al. 2010).
Aprea et al. 2016; Baltova and Dimitrov 2014; Anxiety increases VSCs levels in the breath as
Smith et al. 2016; Venkateshwarlu et al. 2004). it is associated with hyposalivation; however the
In chronic alcoholics, multiple factors play key diagnosis of anxiety is challenging as even if an
roles in causing oral malodor. Aldehydes that are individual has insight regarding their condition,
primary metabolites of ethanol can cause more they are unlikely to report it. This is likely due to
harmful effects than alcohol itself due to its the social stigma with mental health illness which
increased volatility and greater readiness for inter- remains significant in today’s society.
action with tissues (Suzuki et al. 2009). Further- Pseudo-halitosis on the other hand may be
more, if alcohol consumption is coupled with related to a fear of social interaction due to per-
smoking, chewing tobacco, or chewing betel, ceived malodor, which sufferers perceive as very
this induces oxidative stress on the tissues and bad, until there is objective evidence that this is
causes DNA damage and cytotoxicity. In addition, not the case. Many are then re-assured, but some
alcohol can cause oral dryness which can lower hold on to their belief despite the complete
the pH resulting in VSCs production in addition to absence of any objective halitosis. Such individ-
the volatile nature of alcohol itself (Suzuki et al. uals fall into the category of halitophobic, and
2009). these individuals express a conviction that others
think that they smell. Patients with delusional
Psychogenic Factors halitosis or halitophobia believe that they have
In case of psychogenic malodor, the psychologi- bad breath, although many have never asked any-
cal state of the sufferer may increase or decrease one for an objective opinion. They persist in their
the levels of objective malodor (Akos et al. 2012; belief despite reassurance, treatment, and counsel-
Pham 2013). Although this has not been satisfac- ing (Alzoubi et al. 2015; Suzuki et al. 2009; Eli
torily proven, the possible exception to this is the et al. 1996). Halitophobia may severely affect the
effect of stress which may have secondary impli- lives of some 0.5–1.0% of the adult population;
cations for halitosis due to diminished salivary however, there is no generally agreed treatment
flow (Singh et al. 2015). Under stress, individuals protocol with some cases being treated with anti-
may develop hyposalivation, which leads to a depressants, antipsychotics, or psychotherapies
longer retention time of the biofilm matrix. This (Eli et al. 1996). The condition may indicate
results in a greater degradation rate of retained underlying neurosis or psychosis and may indi-
proteins in the mouth and consequently increased cate depression or obsessive compulsive
16 J.R. Thoppay et al.

behavior, necessitating psychiatric care (Arenas designed to understand underlying psychosomatic


et al. 2013). conditions has similar questions scattered
throughout the questionnaire in order to be dis-
guised. Any such screening questionnaire pro-
Patient Management vides an opportunity for verbal inquiry to assist
in establishing rapport and facilitate the clinician’s
Clinically, patients complaining of halitosis may better understanding. Individuals with pseudo-
have actual malodor or may present with pseudo- halitosis have a greater tendency toward neurosis
halitosis. A systematic approach is often neces- than subjects with physiologic halitosis or oral
sary. Patients with genuine halitosis or pathologic halitosis. A thorough understanding
halitophobia, irrespective of the type, suffer sig- of this condition and the clinician’s scope of
nificant impact on overall quality of life (Buunk- knowledge as well as defining their role managing
Werkhoven et al. 2012). The algorithm shown in this condition is essential. Patients who may have
(Fig. 13) illustrates a stepwise assessment plan underlying systemic conditions or psychiatric fac-
(Kapoor et al. 2016; Dal Rio et al. 2007). A tors may need appropriate referral for manage-
clinical questionnaire (Yaegaki and Coil 1999) ment (Seemann et al. 2014).

Chief
Complaint

History of present
illness

Assessment Subjective and Objective, Medical History, Medications, Social History, Clinical findings,Dental disease, Periodontal disease, Food
impaction, Xerostomia, Salivary gland hypofunction, Oral lesions.
Diagnostic tests, organoleptic tests, characteristic odor for local or systemic conditions.

POSITIVE CLINICAL FINDINGS NEGATIVE CLINICAL FINDINGS

Genuine Halitosis Pseudohalitosis

Physiologic Halitosis Pathologic Halitosis

Oral Halitosis Extraoral Halitosis

Non Blood borne Blood borne

TN1, TN1, TN1, TN1,


TN1 TN3
TN2 TN3 TN4

Patient reports subjective complaints of halitosis without objective physiologic


or pathologic findings

Halitophobia

TN 5

Fig. 13 Halitosis diagnostic algorithm (TN – Treatment needs, explained in Table 5)


Halitosis 17

Table 5 Halitosis and treatment needs


TN
stage Presentation Recommendations
TN-1 Physiologic or pathologic malodor, genuine • Patient education
halitosis, predominantly local cause, occasionally • Oral health maintenance inclusive of home care,
Pseudo or transient halitosis tongue cleaning, brushing, flossing antimicrobial
mouth rinses, dentifrices, periodic dental evaluations,
and oral hygiene visits
TN-2 Genuine halitosis, predominantly pathologic due to • Periodontal treatment and comprehensive dental care
local factors, periodontal and dental disease, dry including, extraction of non restorable teeth,
mouth management of oral lesions if present, management of
dry mouth, endodontic treatment, restoration, dental
prosthesis if necessary
TN-3 Genuine halitosis, predominantly extra-oral cause • Referral to physician or medical specialist as
due to systemic diseases, non- blood borne and applicable
blood borne
TN-4 Predominantly pseudo-halitosis • Patient education and counseling
• Oral hygiene measures including tongue cleaning
TN-5 Possible halitophobia and pseudo-halitosis • Patient education and counseling
• Referral for psychiatric evaluation and management

History and Evaluation possible oral causes for halitosis. Therefore, a


thorough knowledge and understanding of halito-
Subjective and objective assessment: Halitosis sis is essential as the etiology is often
is not an all or nothing state. Very few individuals multifactorial.
have zero scores on the organoleptic scale which Self-assessment: The majority of patients
is an intensity scale to measure malodor that (93.9%) with the primary complaint of halitosis
ranges between 0 and 5, 5 being very intense have objective evidence of halitosis as judged by
malodor, where the vast majority of individuals organoleptic methods; however there is an incon-
have breath levels between 1 and 5, with slight sistent correlation between self-assessment and
variations (0.5 units) throughout the day. Clini- clinically detectable causative oral disease.
cally, patients complaining of halitosis may have Patients with mild-to-moderate halitosis have the
actual malodor (low, intermediate, or high) or may highest correlations between self-assessment and
not have malodor to the extent to which they odor assessment of halitosis (Aimetti et al. 2015).
perceive. The dichotomous approach (malodor/ A recent study found a good correlation between
no malodor) allows clinicians to use a cutoff patients’ self-estimation and clinical oral malodor
point on one or more measurement scales (e.g., (Kapoor et al. 2016). It suggested that self-
from Halimeter, oral chromatography, signal estimation of oral malodor by using the hand-on-
intensity of precursor ions in flow tube mass spec- mouth technique was useful in the assessment of
trometry [SIFT-MS], or organoleptic judge) to risk factors and detection of one’s own malodor
support the division of halitosis/non-halitosis which increased the accuracy of patients’ estima-
cases. The majority of patients complaining of tion of their oral malodor (Pham 2013).
halitosis are likely to seek advice from a dentist History of present illness: A detailed history
or their general medical practitioner. A minority of and evaluation that includes a thorough under-
patients seek help from a specialist in gastroenter- standing of the patient’s complaint and analysis
ology or otorhinolaryngology, who typically only of subjective and objective presentation are man-
assesses and treats sources of halitosis related to datory. Genuine halitosis as opposed to pseudo-
their specialized area. If there is no obvious source halitosis must be assessed. In the case of genuine
of halitosis, the patient will likely be referred to an halitosis, evaluation should include a detailed his-
oral health care provider for further assessment of tory of oral malodor, triggers, duration,
18 J.R. Thoppay et al.

aggravating, and relieving factors (Akos et al. 2016). The organoleptic method is the “gold stan-
2012; Al-Zahrani et al. 2011). dard” and is the most widely used scoring system
Health history: A detailed health history that for ranking halitosis using the organoleptic score
includes medical history, medications, including (Scully et al. 1997).
over the counter products and nutritional sub-
stances, should be noted. Social habits such as
smoking, alcohol consumption, and substance Diagnostic Tools
abuse may be underlying causes of halitosis.
Review of systems may facilitate ruling out any Diagnostic tools for assessment of halitosis may
underlying cause that may be missed from the include devices that measure VOC/VSC by gas
medical history (Akos et al. 2012). It is also chromatography. The gas chromatography
important to relate the symptom of halitosis to method measures the concentration of volatile
clinical presentations of dry mouth, saliva pH, sulfur-containing compounds in samples of
dental caries, periodontal disease, the presence saliva, tongue coating, or expired breath by pro-
of oral lesions, and overall oral health. Any asso- ducing mass spectra (Schmidt et al. 2015). Clini-
ciations with underlying systemic conditions cally, these tools such as Oral ChromaTM (FIS A
should also be accounted for (Murata et al. Nissha Company, Japan/Abiliti Corporation,
2002). Patients may have multiple factors contrib- Chuo-ku, Osaka, Japan) (Fig. 14) (Sinjari et al.
uting to halitosis, and these may be a combination 2013) and HalimeterTM (Interscan Corporation,
of medication, food, local, systemic, and psycho- USA) (Fig. 15) have been reliable in measuring
logical causes (Rosing and Loesche 2011; oral malodor. HalimeterTM identifies VSCs in
Tangerman 2002; Madhushankari et al. 2015; Eli breath produced by anaerobic bacteria, which
et al. 1996; Singh et al. 2015). When it is deter- can be read in a graph, the Haligram (Fig. 15);
mined to be strictly psychogenic, pseudo-halito- however, this product is currently not readily
sis, or halitophobia, the patient should be referred available in the market. HalisensTM
for psychiatric evaluation and management (AI Analytical Innovations, Moosbach, Germany)
(Akpata et al. 2009). (Fig. 16) breathometer device analyses breath and
can be connected to a smart device to track oral
malodor. Oral ChromaTM is connected to a com-
Clinical Presentation puter with a specific software program that allows
graphic creation, which corresponds to the peaks
There are various diagnostic methods that have and concentrations of VSCs ranging 0–2913 parts
been traditionally used by clinicians to effectively per billion (ppb) with precision after about a few
diagnose this condition. This includes self- trials. A chromatogram helps to assess the levels
assessment, which sometimes prompts patients of volatile compounds. The threshold levels for
to seek care. However, patients cannot smell bad breath are 112 ppb for hydrogen sulfide,
their own breath and rely upon others for this 26 ppb for methyl mercaptan, and 8 ppb for
information. There are primarily three measure- dimethyl sulfide (Sinjari et al. 2013). The results
ment methods of genuine halitosis. They are of these tests may have different influencing fac-
organoleptic measurement, gas chromatography, tors and variation in scales used. Moreover, these
and sulfide monitoring. Additional or alternative measurement methods are not very easily
measurement methods are BANA test, chemical implemented because they require trained exam-
sensors, salivary incubation test, quantifying iners, and are time consuming and costly. Hence,
β-galactosidase activity, ammonia monitoring, for reliability at least two diagnostic methods may
ninhydrin method, and polymerase chain reaction. be used to validate results (Laleman et al. 2014;
There are diagnostic tools available to measure the Brunner et al. 2010).
VOC/VSC in exhaled air, which may be very Organoleptic measurements: The human
useful to assess the condition (Kapoor et al. nose remains the “gold standard” in detecting
Halitosis 19

Fig. 14 (a) OralChroma™ separates VSC in oral breath (Images courtesy of FIS A Nissha Company, Japan/Abiliti
into hydrogen sulfide, methyl mercaptan and dimethyl Corporation, Chuo-ku, Osaka, Japan)
sulfide (b) Sample being loaded into OralChroma™

Fig. 15 (a) Halimeter (b) Haligram showing the emitted levels of VSO (Images courtesy of Interscan Corporation, CA, USA)

oral malodor (Seemann et al. 2014). The most coffee, tea, or juice and abstain from smoking
widely used scoring system for ranking halitosis and using scented cosmetics before the assess-
is the organoleptic measurement, which is a sen- ment process.
sory test scored by the examiner’s perception of a For the assessment to be effective, the patient is
subject’s oral malodor. The reason for which the also required to adhere to stringent instructions
organoleptic score remains the gold standard for which include:
breath measurements is that the human nose is
capable of sniffing and defining odors as pleasant • Abstain from taking antibiotics for 3 weeks
or unpleasant. That is, the human nose is capable before the assessment
to detecting unpleasant odors such as VSC as well • Abstain from eating garlic, onion, and spicy
as other organic compounds from exhalation foods for 48 h before the assessment
(Rosenberg and McCulloch 1992). The examiner • Avoid using scented cosmetics for 24 h before
performs the sniff test and scores by sniffing the the assessment
patient’s breath and scoring the level of oral mal- • Abstain from ingesting any food or drink at
odor. The examiner should have a normal sense of least 3–4 h before the test, and to omit their
smell and is required to refrain from drinking usual oral hygiene practices
20 J.R. Thoppay et al.

Fig. 16 HaliSensTM VSC


monitor with sample loaded
for analysis (Image courtesy
of AI Analytical
Innovations GmbH,
Moosbach, Germany)

• Abstain from using oral rinse and breath examiner sniffs the severity of the odor at a dis-
fresheners tance of 20 cm. The purpose of using a pipette is to
• Abstain from smoking for at least 12 h before lessen the intensity of expiring air. The tube is
the assessment (Kim et al. 2010; Coil et al. inserted through a privacy screen (50–70 cm)
2002) that separates the examiner and the patient which
facilitates the effectiveness of the test. An organ-
Organoleptic scales: The organoleptic scale oleptic score [OS] of 0 on the scale is <5 ppb
focuses on the objective strength of the smells in hydrogen sulfide, while a score of “1” might
question (target odors) including on occasion typically be a 5 times higher gas concentration
“pleasant” smells (e.g., mint flavored mouth- than a score of zero (i.e., 25x). That is, a score of
washes). The hedonic scale on the other hand is 2, 3, 4, and 5 would be equivalent to 125, 625,
more in tune with the subjective feelings of the 3125, and 15,625x higher concentrations,
perceiver in judging smells as “nice” or “nasty” respectively. In contrast, all breath gas analysis
rather than weak or strong smell of target vola- instruments show linear responses (Murata et al.
tiles. It should be noted that the organoleptic scale 2002). This is important for correlation between
is what is described as an exponential scale, anal- the OS and the instrument in question. The
ogous to decibel for hearing, or lux for luminosity. instrument readout values must be log-plotted
In the organoleptic test measurement, the against OS in order to achieve a straight-line
patient takes a breath by deeply inspiring the air correlation, from which parametric rather than
by nostrils and holding awhile, then expiring by nonparametric statistics can be used for compar-
the mouth directly or via a pipette, while the isons (Greenman et al. 2004).
Halitosis 21

The organoleptic scale by Rosenberg and simultaneously in real-time measurements.


McCulloch (1992) (Greenman et al. 2014) uses a Whichever gas analytic method is chosen, provid-
6-point scale for testing chlorhexidine against a ing the instrument is quantitative for the target
two-phase mouthrinse with scores of 0–6 as VSCs, the outputs can be log plotted against the
follows: organoleptic scores obtained whenever the two
methods are applied together on the same “sam-
1. No odor ple”. Such correlations show the organoleptic
2. Barely noticeable odor method to be a valid quantitative method (Szabo
3. Slight odor et al. 2015). Nevertheless, the ability of the gas
4. Moderate odor analytic equipment to monitor specific target
5. Strong odor analytes is a clear advantage over the organoleptic
6. Extremely foul odor, later changed to strong method alone, so such equipment is a valuable aid
odor for periodic monitoring and prognosis (Marchetti
et al. 2015; Akos et al. 2012; De Baat et al. 2014;
VSC monitoring: Chemical and instrumental Szabo et al. 2015; Sinjari et al. 2013).
analyses can detect relatively large concentrations Microbiologic tests: VSCs are products
of VSCs; however at lower concentrations these resulting from microbial metabolism within oral
are insufficiently sensitive to detect. Gas chroma- biofilms which partitions between the liquid
tography employing a flame ionization detection phases and the intra-oral headspace gas phase
system can identify methanol, ethanol, and ace- giving the resultant product that is responsible
tone but is less efficient in detecting VSCs. Gas for malodor. An alternative strategy to measuring
chromatography units equipped with highly selec- the gases would be to detect and analyze qualita-
tive and sensitive flame photometric detection tively or quantitatively the microbes causing mal-
systems specific for sulfur compounds can readily odor. A clear relationship has been established
identify methyl mercaptan, hydrogen sulfide, and between the quantity of tongue biofilm (its density
dimethyl sulfide in oral breath. VSCs can be mea- and thickness as a film) and the degree of malodor
sured quantitatively in breath by a gas chromato- (Saad et al. 2016). Microbes associated with peri-
graph equipped with a flame photometric detector. odontal disease, mostly Treponema denticola,
The components can be identified by comparing Porphyromonas gingivalis, and Tannerella for-
the mass spectra with those of a computer-based sythia, produce both VSC and volatile fatty
reference library (Sinjari et al. 2013). Oral acids, detection of which may provide informa-
ChromaTM is an ion trap transportable semicon- tion that contributes to halitosis. Benzoyl-DL-
ductor gas sensor that permits analysis by gas arginine-naphthylamide (BANA) (Fig. 17), a syn-
chromatography and mass spectroscopy (Van der thetic trypsin substrate forming a colored com-
Sleen et al. 2010; van den Broek et al. 2007). The pound due to degradation by enzymes from
VSC monitors detect from 18% to 67% of odors bacterial organisms, can provide additional infor-
that can be effectively matched by the organolep- mation on compounds other than VSCs. However,
tic score. Though most of these compounds can be full microbiological analysis by viable count of
measured, certain compounds such as volatile facultative and strict anaerobes by selective recov-
fatty acids (butyrate, propionate), diamines ery medium and viable count is beyond the major-
(cadaverine, putrescine) and other foul smelling ity of general dental practices or breath research
products can only be measured by laboratory- clinics. However, there are other features of oral
based assays. Though there is equipment avail- biofilms that correlate with the tendency towards
able to undertake this, reliability needs to be bad breath including the proportion of species that
assessed in further studies. SIFT-MS is a relatively produce black H2S-positive colonies on cysteine-
new technique that is ideally suited to the accurate iron agar plates and the proportion of species that
and sensitive analysis of breath and can detect the are proteolytic. The BANA test uses benzoyl-DL-
presence of hundreds of different VOCs arginine-naphthylamide which forms a colored
22 J.R. Thoppay et al.

compound due to its degradation by enzymes or scrape. The BANA test has been found to
secreted from protease positive species. This test correlate significantly with the organoleptic
is a chair-side exercise that can be completed in scores obtained from the whole mouth, the
5–10 min and measures levels of enzymes tongue, and saliva, but less so with VSC
expressed in situ, directly from a biofilm sample (Kozlovsky et al. 1994; De Boever et al. 1994).
Oral health management: Maintaining
proper oral hygiene has been reported to minimize
local causes of halitosis. Comprehensive dental
care including extraction of nonrestorable teeth,
management of oral lesions if present, manage-
O
ment of dry mouth, endodontic treatment, and
NH
fabrication of dental prostheses can provide a
HN
foundation for eliminating local causes of mal-
odor. Periodontal therapy, where appropriate, can
O HCI facilitate reduction of halitosis (Kamaraj et al.
2011; Stamou et al. 2005; Kuo et al. 2013).
HN Mechanical methods: Tongue cleansing is
NH2 one component of oral health maintenance, how-
ever rarely the sole treatment for halitosis
HN
(Ademovski et al. 2013; Erovic Ademovski et al.
Fig. 17 N-α-Benzoyl-DL-arginine naphthylamide hydro- 2012). Mechanical interventions such as tongue
chloride [BANA] scrapers and tongue brushes (Fig. 18) physically

Fig. 18 Various tongue scrapers and brushes. (1) Stainless and built-in scraper. (3) The Tongue CleanerTM. (4) Tongue
steel tongue scraper. (2a) OraBrush1 with soft tongue- scraper with Bristles on one side and scraper on the other
friendly bristles modelled on a surgical cleaning brush. side. (5) BreathRxTM tongue scraper made of flexible
(2b) Orabrush1 with ultra-soft, micro-pointed bristles material
Halitosis 23

a chemical intervention (Saad et al. 2016; Roldan


et al. 2005).
Masking agents: Masking agents are com-
monly used as the first-line therapy for individuals
who have self-diagnosed oral malodor. Use of
breath mints and chewing gum are common prac-
tices and easily accessible. These approaches may
provide temporary relief for individuals by
increasing salivary secretion and are especially
beneficial in managing transient malodor (Shiyao
et al. 2015; De Luca-Monasterios et al. 2014). In
addition, masking agents can play a major role in
alleviating halitosis when direct treatment
approaches to the underlying cause are limited.
Similarly mouth rinses containing chlorine diox-
ide and zinc salts (Table 4) significantly reduce
oral malodor. Both chlorine dioxide and zinc salts
are biocidal and biostatic compounds that kill or
reduce the growth and metabolism of biofilm spe-
cies. Both are also strong oxidizing agents able to
alter the biofilm redox and reduce the activity of
cysteine desulfhydrase (the enzyme responsible
for H2S production) (Aydin et al. 2016). The
higher (more oxidative) redox also inhibits
cysteine-dependent protease activity, including
trypsin-like protease from periodontal pathogens.
Fig. 19 Sonicare TongueCare+TM This is facilitated by zinc as it is a strong inhibitor
of proteolysis. In addition, the zinc ions form
remove bacterial biofilms from the tongue sur- insoluble sulfides (ZnS), reduce the concentration
face; however mechanical interventions only pro- of liquid phase H2S, and thus reduce the volatili-
vide transient protection that lasts for as little as zation of H2S and the consequential unpleasant
30 min (Seemann et al. 2014). A combined odor. The reactive thiols found in local oral hali-
approach using a newly designed sonic tongue tosis can be bound to zinc salts and can be neu-
brush with an antimicrobial spray has been tralized and effectively withdrawn from the breath
reported to reduce bad breath over a prolonged (Tangerman and Winkel 2007, 2010; Kappler and
period of at least 6 h. An example of such product Schafer 2014). Examples of currently available
is Sonicare TongueCare+TM (Fig. 19) which is products are listed in Table 4.
available in the US market and reports to kill Antimicrobials: Treatment approaches that
99% of odor causing bacteria using an alcohol- impact colonization of VSC-producing bacteria
free tongue spray with antibacterial in the oral microbiota have the potential of reduc-
cetylpyridinium chloride (CPC) and Zytex™ to ing halitosis. Mouth rinses containing chlorhexi-
neutralize VSC gases, in a thick, concentrated dine have been found beneficial in reducing
formula that lubricates the tongue for a gentle microbial activity (Roldan et al. 2005). Rinsing
clean (Saad et al. 2016). The sonic action pro- with a zinc acetate and chlorhexidine diacetate
duces about 31,000 vibrations per minute to containing mouth rinse resulted in a clinically
break the tongue coating effectively. A higher relevant reduction of intra-oral halitosis during a
reduction in malodor and bacterial density has study period of 2 weeks (Erovic Ademovski
been achieved by combining a mechanical with et al. 2012). Also mouth rinses containing
24 J.R. Thoppay et al.

Table 4 Products effective for oral malodor reduction (Ref: http://www.tordent.com/pdfs/all%20handouts1.pdf; Aydin
et al. 2016; Shiyao et al. 2015; De Luca-Monasterios et al. 2014)
Products Active ingredients Mechanism of action Examples
Masking Flavoring agents such Temporary relief by masking Breath mints, chewing gums,
agents as mint extracts that mouthwashes
mask oral malodor
Chemical Zinc salts (chloride, Biocidal and biostatic compounds a. Toothpastes – TriOral, Listerine
products for citrate, acetate) providing sustained breath odor Tartar Control, Viadent Advanced
oral malodor reduction for 3 h by reducing the Care, Aim TC, Close-Up, TC, Kiss
reduction activity of cysteine desulfhydrase, My Face Tartar Control, Smart
form insoluble sulfides (ZnS) Mouth Toothpaste
reducing the concentration of liquid b. Mouthwashes – Lavoris,
phase of H2S Listermint, Listerine
Tartar control
Chlorine dioxide Biocidal and biostatic compounds a. Toothpastes – Oxyfresh, CloySys
(sodium chlorite) providing sustained breath odor II, Therabreath, Profresh
reduction for 3 h b. Mouthwashes – Oxyfresh,
CloSys II, Therabreath, Enfresh,
Profresh
Essential oils Menthol, thymol, Sustained breath odor reduction for a. Toothpastes – Listerine EC paste
eucalyptol 3 h by masking, neutralizing and and gel, Breath-So-Fresh
biocidal activities Toothpaste
b. Mouthwashes – Listerine EC
mouthwash, many store brands
Antimicrobial Chlorhexidine, Biocidal, antimicrobial activity on Mouthwashes-Peridex, Gum
agents cetylpyridinium odor causing bacteria Perioshield
chloride, amine
fluoride-stannous
fluoride
Note: Brand names may vary depending on the country of origin.
Commercial products (containing combinations of two of the above effective ingredients).
TherabreathTM mouthwash and toothpaste, Smart Mouth chlorine dioxide and zinc chloride, Breath-So-Fresh essential
oils and salts, Oxyfresh Zinc chlorine dioxide and zinc chloride

low concentrations of chlorhexidine (0.05%), reacting with oxygen in a medium to cause reac-
cetylpyridinium chloride (0.05%), and zinc lactate tive oxygen species. This reaction results in a
(0.14%) are effective in the treatment of oral mal- phototoxic effect on microbes providing antimi-
odor (Kang et al. 2015). Morning breath odor can crobial activity to the tissues exposed to PDT. The
be successfully reduced by the sole use of an dorsal tongue is targeted and treated, resulting in
amine fluoride-stannous fluoride-containing an antimicrobial effect on odor causing microbes,
mouth rinse twice daily, which significantly thus reducing oral malodor (Costa da Mota et al.
reduces the bacterial load in saliva and retards 2016; Lopes et al. 2014, 2016).
plaque formation (Quirynen et al. 2002); however, Medical approaches: Extra-oral halitosis may
an adverse effect of this mouthwash is staining be a manifestation of a serious underlying disease
(Fig. 20) of the dorsum of the tongue (Winkel and contributes to 5–10% of all cases of halitosis.
et al. 2003; Zhang et al. 2014). Treatment for extra-oral halitosis is much more
Photodynamic therapy: Recent preliminary complicated than for intra-oral halitosis. Odor
studies highlight the use of photodynamic therapy characterization of various odorants in patients
(PDT) for oral halitosis (Costa da Mota et al. with halitosis may serve as a possible mode for
2016). PDT involves the use of a non-toxic pho- identification of underlying medical conditions.
tosensitizer along with visible light that facilitates For example, renal failure is associated with a
a state of excitation after absorbing photons and fishy odor (Table 1). In addition, standard gas
Halitosis 25

cause psychiatric issues leading to anxiety due to


halitosis (Coil et al. 2002; Suzuki et al. 2008).
Delusional halitosis may have occurred in these
patients due to possible underlying psychoso-
matic tendencies. Generally, patients with delu-
sional halitosis fail to recognize their
psychosomatic condition, but a number of them
interpret other people’s behavior as response to
their own bad breath. The most common associ-
ated oral factor is abnormal taste and occasionally
followed by extra-oral factors and invasive dental
treatment (Akpata et al. 2009) aggravated by
stress (triggering) to a perception of oral malodor.
Careful accounting for such presentations is crit-
ical for effective management. Patients with pos-
sible effect due to their emotional state causing or
aggravating their oral malodor may benefit from
early referral to a psychiatrist for mental health
assessment and appropriate management which
can alleviate the perception of oral malodor. Con-
Fig. 20 Areas of discoloration on dorsal tongue after sequently, treatment needs [TN] in a stepwise
mouthwash use manner as illustrated in the management algo-
rithm (Fig. 13) are determined by the classifica-
tion of halitosis based on etiology. These are listed
chromatography facilitates specific sulfur detec- as TN-1 through TN-5 as illustrated in Table 5.
tion, which helps to easily differentiate between Individuals who present with self-diagnosed oral
intra-oral and extra-oral blood-borne halitosis, as malodor typically attempt to self-manage using
these two forms are nearly always caused by the local oral care measures (Table 6). Management
presence of VSCs (Tangerman and Winkel 2010). of patients based on treatment needs is essential
Referral to a physician or medical specialist based due to the multifactorial etiology of halitosis.
on the characteristic malodor and underlying Many patients may have overlapping etiologies,
medical condition is essential. A multimodal which may challenge the clinician. Patients with
approach may be necessary. This may include systemic sources of halitosis, pseudo-halitosis or
providing antimicrobial mouthwashes and halitophobia require a multidisciplinary
masking agents, comprehensive oral care, man- approach.
agement of oral dryness, and of course medical
management of the underlying condition (Roldan
et al. 2005). Conclusions and Future Directions
Psychosocial approaches: Adverse psycho-
logical aspects of these patients may lead to clin- Halitosis is a common problem with many etiolo-
ical misjudgment and mismanagement, in which gies. Although local causes may contribute pre-
case, it may be challenging for clinicians to deal dominantly; underlying systemic causes may
with patients with psychological conditions such co-exist in 5–10% of patients with this condition.
as pseudo-halitosis or halitophobia. Using an Individuals may also present with pseudo-halito-
appropriate questionnaire may facilitate screening sis or halitophobia which are challenging condi-
for psychiatric disorders (Yaegaki and Coil 1999). tions to manage, especially when coupled with
Patients may have underlying psychiatric condi- periods of genuine halitosis. In these cases,
tions, or the presence of genuine halitosis may unraveling the psychosocial factors at play is
26 J.R. Thoppay et al.

Table 6 Commercial products for local control and prevention of halitosis


Management Products
Mechanical Tongue cleaners, toothbrush, interdental cleaning and flossing, professional oral hygiene
care such as prophylaxis and scaling
Over the counter products Breath mints, chewing gums, breath sprays, lozenges-containing breath refreshers,
Peg-40 hydrogenated castor oil – a polyethylene glycol computation, baking soda
Products for oral Chlorhexidine, triclosan, hydrogen peroxide, OXYD-8[R] – a derivative of sodium
microbial control chlorite, oxidizing lozenges, amine fluoride/stannous fluoride

prudent. Despite the many etiological factors


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