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Halitosis: etiologic classification for research and clinical settings

Abstract
Halitosis research has been held back by a marked lack of consensus as to how to define, classify, diagnose, quantify and treat halitosis. Consequently there is great variation in the methodology and results from one publication to the next, inter-study comparison is made difficult, and evidence-based treatment protocols are difficult to derive.

Previous classifications were analysed, and all contained various degrees of flaws which limited their utility for research and clinical use. None were considered suitable for use in modern, evidence-based medicine.

We present a new etiologic classification which supersedes these problems and is intended to provide standardization. The most accurate way to model halitosis is by considering it according to etiology, viz: type 0: physiologic odor (present transiently to varying degrees in all normal healthy subjects, and underlies any pathologic cause of halitosis); type 1: oral halitosis (halitosis caused by an intra-oral pathology, e.g. tongue coating); type 2: airway halitosis (caused by pathology of the respiratory tract, e.g. rhinosinusitis, bronchial carcinoma); type 3: gastroesophageal halitosis (caused by leak of volatiles from the esophagus and stomach, e.g. erosive gastroesophageal reflux disease); type 4: blood-borne halitosis (caused by transfer of odorant volatiles from the systemic circulation during gas exchange, i.e. pulmonary excretion; e.g. fetor hepaticus) and type 5: subjective halitosis (a halitosis complaint in the absence of clinically detectable odor, e.g. olfactory reference syndrome, chemosensory dysfunction).

For research, this etiologic classification is badly needed to standardize research methodology. Clinically, this model is ideal to aid diagnosis and referral in case of multidisciplinary management.

Keywords: halitosis, review, classification, definition, etiology

Introduction
Halitosis is a complex topic, but most often represent benign processes. It is a cause of social anxiety due to the attached stigma. This is largely the result of commercial advertising pressures, but there is also an instinctive evolutionary aversion of malodor that is present to help detect potentially harmful substances such as spoiled food, or indeed to help identify health status of potential mates and to avoid potentially infectious individuals. Concern over bad breath is a common trigger to seek dental care, yet many dental schools teach little about how to manage this clinical problem. Halitosis has been receiving increasing scientific interest in recent times, but the situation is plagued by lack of consensus in many areas.

Epidemiology
The prevalence of halitosis in the general population is estimated at 3.4 to 29% according to the largest samples available (n=384-2672). Precise estimates of the contributions from the various possible etiologies of halitosis are also difficult to derive due to the lack of standardization, but also much data are from specialist halitosis clinics. The true picture of halitosis cases can only be obtained by analysis of the general population or in attendees in the general dentistry setting. The vast majority of halitosis patients will never be referred to a halitosis specialist and therefore causes such as periodontal disease may be under-represented in some reports. 5‑72% of all patients who complain of halitosis may represent subjective complaints with no genuine odor. This wide variation is testament to the disagreement in how to diagnose halitosis. There is general agreement that in about 90% of patients with objective halitosis, the cause of the odor is within the mouth. The main causes of intra-oral halitosis are release of volatile sulfur compounds (VSC) from bacterial putrefaction of sulfur containing amino acids on the dorsoposterior tongue, within periodontal pockets and gingival crevices, and saliva. Much can usually be done to alleviate intra-oral halitosis by simple adjustments to oral hygiene practices, e.g. gentle tongue scraping or tongue brushing, non-alcoholic antiseptic mouthwash, flossing, etc. In the remaining 10% of cases, halitosis is caused by various processes outside the mouth, termed extra-oral halitosis. This is a relatively poorly understood area, and opinions differ as to the prevalence of the many cited causes. According to the literature, and with varying degrees of evidence, halitosis can be caused by sinonasal, laryngopharyngeal, gastroesophageal, pulmonary, metabolic and systemic diseases. Some state that the tonsils are the most common cause of halitosis outside the mouth, and that the majority of patients with idiopathic halitosis actually have chronic tonsillitis. Others, that the nasal cavity is the most significant cause, e.g. nasal obstruction causing mouthbreathing and consequent xerostomia. However, others report that mouth breathing is not associated with halitosis. Upper respiratory tract pathology is reported to account for about 4-10% of objective halitosis cases according to some. Others report that most extra-oral halitosis occurs via the blood borne halitosis mechanism (pulmonary excretion of odorant volatiles from the systemic circulation).

Definition
A halitosis complaint may be objective, where there is an unpleasant odor endogenously produced anywhere in the body, emitted from the mouth and/or nose and detectable to others; or subjective, where there is no detectable odor to others but the patient complains of its presence. Anyone who complains of halitosis, objective or subjective, should be considered a “halitosis patient”. Objective halitosis has been defined as "malodor with intensity beyond a socially acceptable level perceived".[7] This is independent from halitometric readings and subjective odor descriptions.

Evidence of objective halitosis is a clinical picture built from all available sources, importantly reliable reports from the patient's social environment (e.g. family/partner/close friends). Single occasion halitometric readings and organoleptic tests should not be relied upon due to the transient nature of the symptom.

It may be the case that the previously black and white thinking of objective halitosis on the one hand and psychologic halitosis on the other is oversimplification. Instead, it might be more accurate to consider a spectrum, with entirely subjective halitosis at one extreme and entirely objective halitosis with no psychologic concern at the other. Most patients will fall somewhere between these two points. When objective halitosis has not been treated, it may cause the patient distress or social isolation, and eventually over-concern about halitosis may develop. Even after the odor is reduced to physiologic levels, the negative psychosocial sequalae may persist, making these cases difficult to treat. Conversely, oversensitivity to physiologic odor may be the basis of a subjective halitosis with no history of objective halitosis.

Classification
A new classification was derived, elimintaing the problematic aspects of previous systems whilst retaining the favorable aspects. Also, new concepts were needed based on the observation that (i) all healthy indiviudals will have breath odor, intermittently and to varying degrees; and (ii) it is possible that more than one cause of halitosis is present in any one individual.

Each etiology of halitosis is assigned a type:


 * Type 0 physiologic halitosis
 * Type 1 oral halitosis
 * Type 2 airway halitosis
 * Type 3 gastroesophageal halitosis
 * Type 4 blood-borne halitosis
 * Type 5 subjective halitosis

Halitosis is the sum of all these mechanisms, although in many cases one or two types will contribute the greatest amount. If any type 1-5 is present, it is superimposed on physiologic odor (type 0). The classification also allows for multiple diagnoses in the same patient, which can be recorded as Type 1+2, Type 1+4 etc. Previous classifications oversimplify halitosis, and this new classification is the most representative model proposed.

Type 0
Type 0 (physiologic odor) is the combined sum of the physiologic contributions of oral, airway, gastroesophageal, blood-borne and subjective halitosis. Physiologic odor is potentially present in all individuals since there is a physiologic level of oral and respiratory tract bacterial activity. There is also the potentially negligible contribution of odorant gas leakage from the gastroesophageal tract, and pulmonary excretion of odorants from the systemic circulation during gas exchange. The intensity and composition of physiologic odor is subject to interpersonal variation and variation in the same person from one moment to the next since it is in a state of continual fluctuation, according to factors such as hydration, last food consumed, hormonal influences, salivary flow rate, and others.

Type 1
Type 1 (oral) halitosis the production of odorant volatiles from the oral cavity, then expressed on the exhaled breath. In all persons there is a degree of oral bacterial activity even without any disease being present. The most significant sites of oral bacterial activity are the dorsoposterior tongue and within gingival crevices. These bacteria putrefy substrates (e.g. sulfur containing amino acids), releasing odorants, notably VSC. The 3 most important VSC in halitosis are H2S and CH3SH, and to a lesser extent (CH3)2S. There are also minor contributions of non-VSC gases. The volatiles released during background oral bacteria activity contribute to physiologic odor.

Various conditions are reported to be associated with halitosis, including oral stagnation, poor oral hygeine, xerostomia, periodontal disease, acute necrotizing ulcerative gingivitis, osteoradionecrosis, large carious cavities filled with debris, blood/thrombi (e.g. extraction sockets), mucosal ulceration, interdental food packing, oral prostheses (dentures, orthodontic appliances, bridges), fissured tongue, hairy tongue, fungating tumors, and others.

Type 2
Type 2 (airway) halitosis originates from the respiratory tract itself, at any point from nasal cavity to alveoli. If desirable, this type can be further divided into upper and lower respiratory tract halitosis. A degree of bacterial activity occurs in health on respiratory tract mucosae and especially in the crypt system of the palatine tonsils. This constitutes the physiologic aspect of this mechanism, which may contribute to varying degrees to physiologic odor as a whole.

Halitosis is said to occur secondary to many different respiratory tract pathoses, but often the evidence for this assertion is anecdotal. Examples include: rhinosinusitis, obstructive nasal pathology (causing mouthbreathing and xerostomia),  post nasal drip syndrome (although the existence of this condition is disputed), nasal foreign bodies, rhinoliths, atrophic rhinitis (ozena),  tonsillitis (especially chronic caseous tonsillitis, also tonsilar actinomycosis),   intra-tonsillar cleft stasis, tonsillolithiasis (tonsil stones), laryngitis, tracheitis, bronchitis, bronchiectasis, pneumonia, tuberculosis,  abscesses (peritonsillar, nasopharnygeal, lung), and carcinomas (nasal, sinuses, pharyngeal, lung).

Type 3
Type 3 (gastroesophageal) halitosis is leakage of odorant volatiles from the esophagus and stomach, which are then transfered to the exhaled breath. This is different from when volatiles are absorbed from the gastrointestinal tract into bloodstream and then transferred to the exhaled breath during gas exchange, which is termed blood-borne halitosis (type 4) rather than gastroesophageal halitosis. The physiologic aspect of gastroesopheal halitosis is created by physiologic gastroesophageal reflux. A degree of gastroesophgeal reflux is considered normal, occuring several times per day, especially after large meals. Gas reflux may be termed eructation, again often occurring after eating or drinking to release swallowed air (in a pronounced form, this is termed aerophagia). However, there is limited evidence that a small degree of gas reflux occurs continuously in healthy subjects without conscious eructation. If this leakage is odorous, it is conceivable that this mechanism could contribute to physiologic odor. A number of gastroesophageal disorders are said to cause halitosis, however this is often controversial, with contradictory reports in the literature. This mechanism cannot presently be dismissed due to widespread methodological flaws in the literature. Examples include erosive gastroesophageal reflux disease (GERD), Helicobacter pylori infection with gastitis, Zenker diverticulum, hypopharyngeal diverticulae and gastrocoloic fistula.

Type 4
Type 4 (blood-borne) halitosis is the transfer of odorant volatiles from the systemic circulation to the exhaled breath, occurring in the pulmonary alveoli during gas exchange (i.e. pulmonary excretion). The concentration of arterial volatiles correlates with the breath concentration. There have been over 3000 VOC detected on the breath of healthy individuals.[95] If odorous, this is the physiologic aspect of this mechanism.

There is much interest in measurement of trace breath volatiles as a non-invasive diagnostic and prognostic tool in many different conditions. However, volatiles must be present on the breath above their detection threshold to cause halitosis, and not every pathology which has demonstrated abnormality of breath volatiles is implicated as a cause of halitosis. Examples of conditions which may cause blood-borne halitosis include liver failure (fetor hepaticus), pancreatic insufficency, kidney failure (fetor uremicus), trimethylaminuria (TMAU), and others.[24,94] Transient halitosis may also occur via this mechanism after ingestion of volatiles foodstufs (e.g. garlic), beverages or certain medications (e.g. disulfiram).

Type 5
Type 5 (subjective halitosis) is a where the patient believes they have halitosis but no odor is consistently detectable to others. Type 5 halitosis can be misdiagnosed if there are measurement errors (e.g. relying on a sulfide detector to diagnose halitosis in a patient with TMAU) or transient odor. This is why reliable reports from the patients social environment are valuable.

It is normal for mentally healthy individuals to worry about their breath occasionally.[121] This can be rationally dismissed by most people. This normal level of halitosis constitutes the “physiologic” aspect of Type 5 halitosis.

The causes of subjective halitosis can be considered as either psychologic or neurologic. Olfactory reference syndrome (ORS) is a mental condition characterized by a persistent belief of the patient's that he/she emits a foul odor when none is actually present. 75% of ORS cases involve a subjective halitosis complaint, sometimes in combination with other body odors.[122] This condition can have significant impact on QOL, including employment loss, divorce or suicidal ideation.[123] However, some report that TMAU or other genuine odor symptoms can be misdiagnosed as ORS.[124]

Neurologic factors that may be implicated in a subjective halitosis complaint include chemosensory dysfunction, for which there are nearly 200 causative conditions reported. [16] Dysosmia (disordered olfaction including parosmia and phantosmia) and dysgeusia (disordered gustation) therefore have extensive differential diagnoses.

Olfaction and gustation are intimately interlinked at the neuronal level in the brain. The definition of subjective halitosis (pseudo-halitosis) has been broadened: “the perception of an alteration in the quality of expired odor air, a symptom perceived only by the patient.”[16] Many patients fail to distinguish between bad taste and bad odor. Gustatory stimuli may influence orthonasal and retronasal odorant perception.[58] Side effects of medication, hypothyroidism, hyposalivation (another extensive differential), nutrient deficiency (zinc, copper, iron, and vitamins A and B12), trauma and tumors involving the olfactory center in the brain, or nerve damage (glossopharyngeal, vagus, chorda tympani, olfactory), neurodegenerative diseases (Parkinson's, Alzheimer’s and Huntington’s disease), environmental pollutants (e.g. smoking), drug abuse, certain oral hygiene products (e.g. mouthwashes) and certain foodstuffs can all be potentially involved in subjective halitosis complaints, by various mechanisms.[16,125] As described previously, diabetes mellitus, GERD and blood-borne stimulation of taste and smell receptors via the blood circulation may also contribute to subjective halitosis.[16,126]

Abstract
Chronic mouth breathing (i.e. consistently breathing through the mouth rather than the nose), especially during childhood, is a reported cause of various problems, including: gingivitis, halitosis, dental malocclusion, abnormal facial growth, hypoxemia, fatigue ...

Introduction
Human infants are sometimes considered obligate nasal breathers, but generally speaking healthy humans may breathe through their nose, their mouth, or both. During rest, breathing through the nose is common for most individuals. Breathing through both nose and mouth during exercise is also normal, a behavioral adaptation to increase air intake and hence supply more oxygen to the muscles. Mouth breathing may be called abnormal when an individual breathes through their mouth even during rest. Some sources use the term "mouth breathing habit" but this incorrectly implies that the individual is fully capable of normal nasal breathing, and is breathing through their mouth out of preference. However, in about 85% of cases, mouth breathing represents an involuntary, subconscious adaptation to reduced patency of the nasal airway, and mouth breathing is a requirement simply in order to get enough air. Chronic mouth breathing in children may have implications on dental and facial growth. It also may cause gingivitis (inflamed gums) and halitosis (bad breath), especially upon waking if mouth breathing occurs during sleep.

In some societies, the term "mouth breather" is sometimes utilized as an insult, intended to imply low intelligence.

Causes
Mouth breathing has been classified according to etiology into 3 groups: obstructive, habitual and anatomic.

Obstructive
The nasal airway may be compromised partially (where there is increased resistance to the flow of air due to narrowing of the lumen at some point in the upper respiratory tract) or completely obstructed. Such individuals may find it difficult or impossible to breath through their nose alone. In about 85% of cases, mouth breathing is an adaptation to nasal obstruction. Specific causes of nasal obstruction which have been linked to mouth breathing include antrochoanal polyps,

"Pregnancy rhinitis" may lead to nasal obstruction and mouth breathing. This tends occur in the third trimester of pregnancy.

Habitual
Some individuals breath through their mouth through force of habit, perhaps due to a previous cause of nasal obstruction that is now corrected.

Anatomic
In other cases, the upper lip may be short, and the lips do not meet at rest ("lip incompetence").

Dental plaque, gingivitis & gingival enlargement
Gingivitis, gingival enlargement,  and increased levels of dental plaque  are common in persons who chronically breath through their mouth. The usual presentation is sharply confined to the anterior maxillary region, especially the incisors, with an erythematous, edematous and shiny appearance of the gingiva. This region receives the greatest exposure to airflow during mouth breathing, and it is thought suggested that the inflammation is related to surface dehydration. In animal experimentation, repeated air drying of the gums did not create such an appearance, suggesting other factors are involved.

Halitosis
Halitosis is reported to correlate with mouth breathing secondary to nasal obstruction.

Many causes of nasal obstruction are also reported to cause halitosis, notably chronic rhinosinusitis. The exact pathophysiologic mechanism of this relationship has never been elucidated.

It is difficult to ascertain whether it is the mouth breathing or the underlying nasal obstruction that may be causing halitosis in these reports. It is reasonable to assume that mouth breathing leads to xerostomia

Some claim that halitosis secondary to sinonasal pathoses is more strongly detectable on the nose breath while the mouth is closed than on the mouth breath when the nares are occluded.

Dentofacial growth & posture
It has been suggested that chronic mouth breathing in children can lead to the development of a long, thin face (termed "long face syndrome", or "adenoid facies" when the mouth breathing is specifically related to adenoid hypertrophy

Malocclusion of the teeth (e.g. "crowded teeth") are also suggested to result from chronic mouth breathing in children.

However, facial form is also strongly influenced by genetic factors. It has been suggested that a long thin face type, with corresponding thin nasopharyngeal airway, predisposes to nasal obstruction and mouthbreathing, i.e. a long thin face may cause mouth breathing rather than the other way around.

The following other conditions are also associated with mouth breathing: cheilitis glandularis, Down syndrome,  anterior open bite,  tongue thrusting habit,  cerebal palsy,  Sleep apnea, Snoring

Abstract
Olfactory reference syndrome is a mental disorder characterized by the patient's belief that they emit foul odor(s), which are undetectable clinically. As ORS patients tend to initially present to physicians and surgeons rather than psychiatrists, and complain of body odor, halitosis, genital odor and/or rectal odor, this condition is of relevance to several specialties including dermatology, dentistry, urology, gynecology and coloproctology/colorectal surgery. In about 70% of cases, ORS manifests as a subjective halitosis complaint with a psychologic basis (which may be termed "halitophobia" in halitosis publications), although many will complain of more than one type of odor. It is important to distinguish between ORS patients and patients with genuine odor complaints to prevent unnecessary medical or surgical treatment, and to direct the patient to a psychiatric colleague. However, ORS is presented in the psychiatric literature in isolation from the differential diagnoses of genuine odor complaints. These unglamorous topics are generally under-researched, with the exception of halitosis for which there is much literature, however the scientific understanding of odor conditions is far from complete, and potential new conditions are in the process of being described.

Traditionally, halitosis complaints have been divided into genuine, objective halitosis and non-genuine, subjective halitosis. There is a tendency to treat these scenarios as mutually exclusive, but it is more accurate to consider these as two extremes of a continuous spectrum. It is now recognized that objective halitosis is often accompanied by psychosocial difficulty, and conversely, there have even been reported cases of patient suicide because of concern for halitosis. The situation is further complicated when one considers that all humans possess a varying degree of physiologic odor, which will be superimposed in any halitosis case, whether objective or subjective. The distress that halitosis causes some patients is known to persist in some cases, even after the odor is successfully controlled. It has been suggested that addressing the psycho-social implications of halitosis is just as great a treatment need as reducing the symptom itself.

The origins of the stigma and taboo that surround halitosis are explored. On the one hand, there is credible evidence that an aversion to malodors may serve as an evolutionary means to detect spoiled foodstuffs, avoid potentially infectious substances and to aid in mate selection. On the other, there is no doubt that in more modern history, commercial pressures in the form of advertising have significantly altered the way the public think about bodily odors, to the extent that psychologic conditions such as olfactory reference syndrome have seemingly materialized out of nothing. Halitosis has been mentioned in the earliest medical texts known, whereas the first report of an ORS-like condition occurred in 1891, and did not become recognized as a distinct entity until much later. Modern consumers now have unrealistic expectations of what constitutes normal, physiologic breath odor, and the many faceted oral hygiene industry drives this obsession.

Keywords: "Halitosis", "Olfactory reference syndrome", "Halitophobia"

Background: Halitosis
Halitosis (or colloquially, bad breath) lacks any accepted definition or terminology, with dozens available in the literature. The most widely used classification (Yaegaki et. al) is arguably not fit for purpose in many regards, but most importantly because it assumes a psychologic basis to all subjective halitosis complaints. In actuality, subjective halitosis complaints may also be explained by mechanisms such as retronasal olfaction and neurologic factors, e.g. chemosensory dysfunction. Among all those patients complaining of halitosis 5-60% are reported to have no objective (genuine) halitosis. This wide variation is at least in part testament to a lack of standardization in research methodologies in halitosis research.

The causes of objective halitosis originates in the oral cavity in about 90% of cases (intra-oral halitosis, or oral malodor). These are most commonly the result of halitogenic biofilm on the posterior dorsum of the tongue, in perioodontal pockets and gingival crevices, and in saliva. The bacteria putrefy sulfur containing amino acid substrates, releasing malodorous volatile sulfur compounds (VSC) such as hydrogen sulfide, methyl mercaptan and dimethyl sulfide. Intra-oral halitosis is generally clinically manageable through cause-related measures such as periodontal therapy or tongue scraping/brushing.

It is clear that halitosis, whether there is a genuine bad odor or a non-existent odor, is a cause of significant anxiety and distress for some people. Further evidence for the great importance that patients place on fresh breath is demonstrated by the existence of a huge oral hygiene industry which manufactures a plethora of bad breath remedies and treatments of every kind. As a result, halitosis is a subject that is receiving increasing scientific interest in recent decades.

Background: Olfactory reference syndrome manifest as a subjective halitosis complaint of psychologic origin ("halitophobia")
The key feature in olfactory reference syndrome is the patient's belief that they emit foul bodily odor(s). There is misinterpretation of the behavior of others to be referential to the patient. E.g., a work colleague declares they are feeling too warm and opens a window. Events such as these can be a cause of significant anxiety for ORS patients. Apart from this feature, ORS is a heterogeneous condition, and may present with a complaint of halitosis, body odor, genital odor, rectal odor, or any combination thereof.

Epidemiology
Since so few cases have been formally reported in the literature, it is difficult to make any firm epidemiological estimates. Cases have been reported from all around the world, perhaps more commonly from Japan and the USA. Some report that females are affected more commonly than males, but the findings of the Arenas ''et. al'' 2013 systematic review reported a roughly equal gender distribution. Among the cases included in this systematic review, the mean age in males was 29, and 40 in females.

ORS is most commonly manifest as a halitosis compliant. Halitophobia is a term coined by Miyazaki et al. who describe it as a belief that there is halitosis which continues after dental treatment, whether this is therapy for genuine halitosis or reassurance that there is no genuine halitosis.

Although the sense of smell is different between genders, it is possible that the female predilection seen in ORS can be explained by a.

There have been reports at attempts to treat these non-existant complaints, e.g. from routine dental interventions to sympathectomy (a procedure normally indicated for hyperhidrosis and other conditions), or tonsillectomy. Patients may have previously attended dentists, dermatologists, ENT specialists and gastroenterologists. Most patients took 8 years for the condition to be diagnosed.

the persistent belief that there is halitosis After treatment for genuine halitosis of pseudo-halitosis, the patient persists in believing that he/she has halitosis 2. No physical or social evidence exists to suggest that halitosis is present

ORS has been compared to: (in the most recent psychobabble from the DSM 5)
 * obsessive compulsive disorder
 * body dismorphic disorder
 * somatic type of the Delusional Disorder
 * social anxiety
 * "jiko-shu-kyofu", a sub type of "taijin-kyofu", (arguably the same clinical entity as ORS)

Diagnosis
Ad hoc diagnostic criteria have been proposed by Philips et al 2006 and then slightly modified by Feusner et al 2010:


 * 1) Concern for the belief that one emits a bad smell, which is not perceived by others (Does not have to have a delusional character).
 * 2) Worry causes significant discomfort (Depressed mood, anxiety, shame ...) or dis-capacity in social, occupational or other areas of functioning.
 * 3) The symptoms are not a symptom of schizophrenia or other psychotic disorder, and not due to the effect physiological substance (drug or drug abuse) or a general medical condition.

These criteria were used in a systematic review of ORS performed in a 2013, appearing in a Spanish language publication.

These patients must be differentiated from patients with genuine odor conditions in order to prevent unnecessary medical or surgical interventions which aim to eliminate a non-existant odor symptom. ORS has been almost exclusively described in the psychiatric literature. It is striking when reviewing these publications how little emphasis is placed on the differential diagnosis of genuine odor symptoms, or indeed organoleptic assessment to rule out genuine odor complaint (in halitosis) when discussing ORS.

There are thousands of medical publications focusing on halitosis, increasingly so in the last decade. However, the scientific understanding of halitosis is not complete, with some potential new metabolic conditions in the process of being described. Other types of odor condition receive less attention than halitosis. Pathologic body odor tends to be referred as bromhidrosis in the literature.

Odor symptoms may not necessarily be continuous, and therefore might be absent during the consultation. A repeat consultation is helpful to support the findings of the initial examination. Periods of life where there are acute odor symptoms, as may be caused by xerogenic medication or by some acute pathology, might trigger the development of an ORS-like condition which persists long after the odor symptom itself is controlled.

For example, a recent study screening a cohort of "idiopathic malodor patients" for TMAU it was reported that a third of the patients were positive for TMAU. The authors suggested that some individuals who have been diagnosed with ORS or similar psychologic conditions may in fact have TMAU. It follows therefore that this suggestion could be applied to other causes of odor generally, and that some individuals have received misdiagnoses, and been labeled with a psychologic condition when in fact they had a genuine odor condition. Indeed, a patient with a real problem who is informed that they have a psychologic condition may then develop further psychosocial problems as a result.

Historically, it is easy to picture a tendency for clinicians to assume a paternalistic approach when presented with a difficult patient complaining of body odor and/or halitosis. This might be justified in the belief that simple reassurance will convince the patient that there is no problem, however it should be remembered that outside the consulting room, the general public generally have no interest in reassuring the patient that there is no odor problem, and their social difficulties may continue. Genuine odors as a symptom with a differential diagnosis have been considered by Brent, 2010, and Shirasu and Touhara 2011. An older series entitled "unpleasant body odors" appeared in Dutch. Brent approached the odor symptom from the emergency room pediatric perspective, and so included several of the in borne errors of metabolism that present with unusual odors in infancy, and also odors associated with various acute intoxications. Shirasu and Touhara present a similarly ambitiously scoped attempt, with particular focus on the Volatile organic compounds (VOCs) involved in various pathologies. In a publication about TMAU, Philips and Shephard state that other causes of offensive body odor fall into 2 categories, namely Those not involving an increase in trimethylamine in the urine (poor hygiene, gingivitis, blood borne halitosis resulting in presence of volatiles other than TMA, such as in dimethylglycinuria); and those resulting in an increase of TMA in the urine (urinary tract infections, bacterial vaginosis, advanced liver or kidney disease, cervical cancer). This division was intended to aid interpretation of TMA urinalysis results in patients complaining of malodor, however, it is evident that the former category is far more extensive than suggested above.

Other publications tend to focus on one type of odor symptom e.g. flatulence,     female genital odor,   body odor and nasal fetor. Halitosis is the most widely researched area of these, with thousands of publications on the topic, a dedicated textbook, dedicated chapters in other textbooks, and an international research society.

Prognosis & Management
It has been suggested that since ORS is a heterogeneous condition, the treatment and prognosis are variable. A large proportion of ORS patients will become unemployed, which they attribute to workplace bullying. In one report, about 30% of patients attempt suicide and > 50% will require a period of hospitalization for psychiatric reasons.

This condition tends to be managed with psychotherapies, and antidepressants or antipsychotics.

In the age of communication, the internet allows patients to access healthcare information more than ever before. This is generally a positive thing, but it also may compound the beliefs of the ORS patient, who spends their time scrolling through health sites and spending their money on products of questionable efficacy instead of living their life. In one reported case, an ORS patient had convinced themselves they suffered from TMAU. Communication between patients with undiagnosed ORS may foster bitterness, as stories of maltreatments by health care practitioners and society at large are exchanged in internet health forums. This may compound sick role behavior and a victimized, segregated mindset.

Halitosis: stigma and taboo, evolutionary vs. socio-cultural influences
Halitosis, and body odors in general, is a subject surrounded by stigma and taboo. It is postulated that this stigma has an evolutionary basis.(Harvery-Woodworth 2013) “Offensive” odors normally trigger repulsion, and it is suggested that this is an evolutionary adaptation to detect and avoid spoiled food or potentially infectious substances. Body odor is also known to play a role in mate selection in humans, perhaps an instinctive drive to avoid mating with sick individuals, and preferentially select mates with dissimilar genes. However, it is pointed out that other mammals, including those species closely related humans, do not seem to posses an aversion to individuals' bodily odors. Indeed the opposite may be true, scent playing a vital role for many species in communicating fertility, territory and cementing social bonds within groups. In human history, breath and body odors were likely not socially unacceptable as they are in modern times. It is hard to picture an ancient human developing a disorder akin to olfactory reference syndrome, when he has more pressing things to concern himself with, such as finding food, shelter and so forth. ORS term first used in 1971, but a case report from 1891 described a very similar condition. In the literature, many terms have been used besides ORS since 1891 to refer to what is arguably the same condition. Such synonyms include

It is interesting to note that those perfumes and fragrances which are considered the most pleasant across many cultures contain olfactory hints of urine. Micro-cultural examples can also be found which seem to contradict an evolutionary basis to the stigma of halitosis. In Ethiopia, there is a tribe called the Dassanetch who consider the smell of cattle to be the most pleasing scent, being associated with wealth and fertility. The males of this tribe are reported to wash their hands in cattle urine and smear their bodies with manure to engineer their scent, much in same way that people form other cultures purchase perfumes to alter and disguise their natural odor. In Mali, a similarly curious example comes from the Dogon people, who consider the scent of onions a desirable body odor, rubbing fried onions on their bodies. It is unlikely that such personal odors would be considered as attractive in Western cultures.

With regards the basis of the stigma and taboo that are attached to halitosis, the authors therefore propose that the influence of evolutionary and instinctive factors may be less than previously suggested, and a far stronger influence can be found in more recent history, where public opinion has slowly been changed by artificial commercial advertising pressures. It is in the self interests of companies to create markets for their products, and a very similar phenomenon can be observed in the history of the manufacture of antiperspirants and deodorants, commodities which ancient humans survived happily without. Indeed it could be argued that the possible allergenic, or even occasionally carcinogenic, nature of these products flies in the face of evolutionary logic. The obsession with fresh breath could therefore be considered as just another facet of a society obsessed with youth, health and cosmesis, and is likely to be largely related to sociocultural factors rather than having any fundamentally significant evolutionary basis. This stigma can become tragic in disorders which lead to chronic, pathological body odor and/or halitosis, such as bromhidrosis or the rare genetic disorder trimethylaminuria, disorders which tend to be largely resistant to treatment for many patients. As a result of the stigma attached to these symptoms, these disorders take on significant psychosocial sequalae,  that otherwise might not be present. Social isolation, depression, anxiety and even suicide have been reported, particularly poignant when one considers that these individuals are essentially healthy in all respects apart form a minor genetic mutation or alteration in the microbiota of the skin or gut.

A middle ground between olfactory reference syndrome and odor conditions. Given how little research interest there is in these topics, and given the partial efficacy of the available treatments, I feel that psychologic interventions to improve coping skills would be infinitely more beneficial to those who profess to have these conditions than closeting themselves away and seeking to only build relationships online, awaiting some far off day when a cure will free them, which in all likelihood will not occur in their lifetime.

Biologically, the fight or flight, sympathetic response is characterized by reduced salivary flow, increased heart rate and respiration rate, increased perspiration, all potential mechanisms by which body odor or halitosis symptoms may be temporarily worsened. Studies have demonstrated that subjects are able to identify sweat from the underarms of people who are anxious (possibly involving alarm pheromones), and differentiate it from people who are happy, based on the odor alone. It is therefore feasible that if the social anxiety is reduced, then the intensity of the odor symptom may be reduced in some cases.

A genuine condition, which is magnified out of all proportion by an ORS-like condition.

The main difference is how they behave, they are not appear as victims, so others do not bully them about it. This is how the quality of life of sufferers can be improved, which is an immediately available goal when compared to "a cure". The average sufferer I spoke to would imagine the problem to be 100% when it is only 15% in reality. And let us not forget the normal, inescapable odor that is present in all healthy people to varying degrees.

The true origins of halitosis, and the term was not put into the publics' imagination as a medical problem, as a problem that prevented social interactions, that required treatment, until a mouthwash company performed an aggressive marketing campaign warning that bad breath would ruin marriage potential. A massive oral hygiene industry later, not to mention soaps, perfumes, etc etc and we have medical conditions where before there was none, and we have associated psychologic conditions, all in the name of profit for the manufacturers of toothpaste, mouthwash, etc etc. It is disgusting when you think about it, but it is just part of a larger picture of how these companies shape consumer demand so they can sell their products. Another good example is plastic surgery, when not so long ago in history people would have just got on with life with their small breasts or large nose.

The evolutionary basis to malodor is weak at best. Imagine cave men being bothered about smelly members of their tribe. Of course there would be no issue, they all would smell terrible. There are tribes in Africa that smear themselves in cow feces because the odor is a sign of wealth. Would "fecal body odor" be a bad thing in this microculture? Imagine a cave man developing ORS? Unlikely, while he is worrying about staying alive and finding food. ORS is a modern pathology, the result of commercial advertising pressure over decades and decades. This would not have happened before 1920. Now we have reports that people kill themselves because they have bad breath.

The so called disease has been materialized out of nothing, and different societies call it a disease and others would not. It is very difficult to treat because it has been made out of nothing. People now have unrealistic expectations of not having any physiologic odor. They might think that a high-normal level odor in the range of normal odors is a disease and they develop a psychologic condition. Lives become dominated by this supposed condition which acts as a subconscious "excuse" not to live life. Because life is scary, it is scary to try and make something of yourself. The mind puts up protective walls which shrink the world down to a much more manageable size. Poor parenting which fails to prepare people for the real world, social anxiety etc etc I'm sure there are many reasons for this mental over-reaction to what may be within the normal odor range, or maybe a minor odor condition. I ask myself why are some people able to be happy day after day with an obvious odor symptom, never let it take over their life, and why others become prisoners in their own home, or even kill themselves over a nonexistent, or perhaps more minor odor symptom? it is another example of how psychopathologies can be just as damaging to the QOL as organic diseases. Ordinary people do not realize how subjective reality is from one person to the next, and how much power their mind has over their experiences.

So in essence, I believe the uniting pathology in this group of patients is a psychologic disorder more than organic disease. The basis of the psychologic disorder might have been only physiologic odor (in which ORS) or a past or continuing minor, genuine pathologic odor condition which gets blown out of all proportion (ORS-like condition). The treatment for both needs to be largely psychologic, instead of waiting for "a cure".

Author's recommendations

 * All patients complaining of halitosis should have a thorough history and examination by a clinician familiar with how to manage halitosis clinically. This includes knowledge of the full range of pathologies capable of causing a halitosis complaint, whether objective or subjective. The basis of the patient's complaint may be an intermittent odor which is not present during the examination. Repeated breath analysis strengthens the findings of the initial consultation.
 * ORS should serve as a diagnosis of exclusion, once causes of objective odor, and non-psychologic causes of a subjective halitosis complaint have been sought and ruled out. ORS patients should be managed in the psychiatric setting, but such patients are not always willing to attend these specialists.
 * Given the stigma and taboo that surround halitosis, patients with objective odor are likely to be distressed. In some of the rarer causes of halitosis, such as blood borne halitosis, the odor symptom is difficult to treat. Psychologic interventions are important to strengthen the coping mechanisms of these patients and are likely to reduce the negative impact on the patient's quality of life that this symptom brings.

Mitchell and Smith classified trimethylaminuria (TMAU) into several sub-types.