INTRODUCTION — Taste and smell disorders are common in adults and may be attributable to a number of causes, including metabolic and endocrine abnormalities, neurologic disorders, inflammatory conditions of the nasal passages and paranasal sinuses, head trauma and surgery, infections, chemical exposures, medications, and even normal aging. Impaired taste and olfaction can negatively impact flavor perception, decreasing the quality of life and interfering with adequate nutritional intake.
The physiology of normal taste and olfaction as well as an overview of taste and olfactory disorders are reviewed here. The evaluation and management of patients with taste and olfactory disorders are reviewed separately. (See "Taste and olfactory disorders in adults: Evaluation and management".)
DEFINITIONS — Normogeusia and normosmia describe normal taste and smell functions, respectively. Definitions of abnormalities of taste and olfaction include:
●Abnormalities of taste function
•Hypogeusia – Diminished taste function to one or more specific tastants
•Ageusia – Absent taste function
•Dysgeusia – Altered (sweet, sour, salty, bitter, or metallic) perception of taste in response to a tastant stimulus
•Aliageusia – Taste disturbance in which a typically pleasant-tasting food or drink tastes unpleasant
•Phantogeusia – Unpleasant taste due to a gustatory hallucination (in the absence of any stimulus)
●Abnormalities of olfaction
•Hyposmia – Diminished smell function
•Anosmia – Absent smell function
•Parosmia – Abhorrent odor perception either with an odorant stimulus (troposmia or smell distortion) or without an odorant stimulus (phantosmia)
•Dysosmia – A general term describing distortion of smell sensations
EPIDEMIOLOGY — Impairment in normal gustatory and olfactory function is common among adults. The prevalence of impaired olfaction increases with age [1-5]. In a study assessing odor perception in over 1200 United States adults, the prevalence of olfactory dysfunction was 4 percent among those ages 40 to 49 years; 10 percent among those 50 to 59 years; 13 percent among those 60 to 69 years; 25 percent among those 70 to 79 years; and 39 percent among those 80 years and older [2]. Anosmia affected 14 to 22 percent of individuals over age 60 years.
In addition to the age of the population, the incidence of olfactory dysfunction depends upon the method of evaluation. In a meta-analysis including over 36,000 healthy adults (average age 63 years old), 29 percent demonstrated olfactory dysfunction on objective testing [5]. In one of the included studies evaluating 3500 adults age ≥40 years, on formal testing, 17 percent had taste impairment, 14 percent had olfactory impairment, and 2 percent had impairment of both senses [6]. The self-reported prevalence of these disorders was lower, with approximately 5 percent self-reporting taste disturbance and 11 percent self-reporting smell disturbance [1]. Olfactory disturbance is reported more frequently than taste impairment since impairment of smell is recognized more readily.
Such disorders can have important clinical implications. Among adults age 70 years and older, for example, misidentification rates for smoke and natural gas were 20 and 31 percent respectively [2]. In addition, there is an association between olfactory dysfunction and increased mortality in older adults [3,7]. As an example, among older adults, anosmia is associated with a higher five-year mortality risk compared with normosmia (odds ratio [OR] 3.37, 95% CI 2.04-5.57) [3].
ANATOMY AND PHYSIOLOGY OF TASTE, OLFACTION, AND FLAVOR PERCEPTION — Taste and olfaction have discrete physiology and anatomy, with each dependent upon unique receptors and neural pathways. Flavor perception is multifactorial, relying upon efferent taste and olfactory input in addition to other sensory information.
Taste — The experience of taste involves the stimulation of taste receptor cells and the subsequent transmission of neural signals via afferent nerves to the central nervous system (figure 1).
Taste receptor cells (neuroepithelial cells) receive information about tastants (taste-stimulating molecules or compounds); the signal is then conveyed to the central nervous system via afferent neurons. Taste receptor cells have an average lifespan of 10 days [8].
Taste buds, which each contain approximately 50 to 150 taste receptor cells, are located on the dorsal and lateral surfaces of the tongue and on the soft palate, uvula, larynx, pharynx, epiglottis, and esophagus [9]. Tastants reach the receptor cells within the taste buds via taste pores, small openings in the epithelial surface.
The lingual (tongue) taste buds are located on structures called papillae. There are three types of papillae, including:
●Fungiform papillae, which are distributed on the anterior two-thirds of the tongue. They vary in number, although the average is approximately 190 per tongue [10]. Approximately 80 percent of fungiform taste buds are located within the anterior 2 cm of the tongue [11].
●Foliate papillae, which are located on the posterior lateral aspect of the tongue.
●Circumvallate, papillae which are located at the rear of the tongue.
Each fungiform papillae contains as many as 20 taste buds, while each circumvallate and foliate papillae can contain hundreds of taste buds [12].
Taste bud containing regions are innervated by three different cranial nerves, the facial nerve (cranial nerve VII), the glossopharyngeal nerve (cranial nerve IX), and the vagus nerve (cranial nerve X):
●The anterior two-thirds of the tongue is innervated by the chorda tympani branch of the facial nerve. The palate is innervated by the superficial petrosal nerve, a different branch of the facial nerve. (See "The detailed neurologic examination in adults".)
●The posterior tongue is innervated by the glossopharyngeal nerve. (See "The detailed neurologic examination in adults".)
●The pharynx and larynx are innervated by the vagus nerve. (See "The detailed neurologic examination in adults".)
The primary afferent taste neurons synapse in the solitary tract nucleus in the medulla. Taste information is then transmitted to the thalamus and primary gustatory cortex [13]. Ageusia (complete absence of taste) is uncommon due to the involvement of multiple cranial nerves in gustatory function.
In addition to afferent taste innervation, other sensory innervation of the oropharynx and nasal cavity impacts the subjective sensation of gustation. As examples, branches of the trigeminal nerve (cranial nerve V) which innervate the interior of the mouth and nasal cavity account for other sensations such as the burning and irritation caused by hot peppers and the fumes of ammonia. Other sensory innervation of the nasal cavity and oropharynx includes the anterior ethmoid, nasopalatine, posterior palatine, and buccal nerves. (See "The detailed neurologic examination in adults".)
Saliva plays an essential role in transporting the tastants through the overlying mucous layer to interact with taste receptor neurons. Taste compounds that are water soluble are delivered readily to the receptor cells, while tastants that are insoluble need carrier proteins for transport to the receptor cells.
Upon delivery of the tastant, activation of protein-coupled receptors induces an alteration in the cell membrane, opening ion channels and allowing depolarization of the neuron [14].
Aberrations in gustatory function can occur if there is any abnormality of any of these structures or functions. As examples, abnormal taste can result from alterations in the composition of saliva or the mucous surrounding the taste buds [15-18], or when there are changes in the taste cell receptor proteins or ion channels [19-21].
Four classic taste qualities are described and typically tested for: sweet, sour, salty, and bitter. A fifth taste, umami, the taste of glutamate, is also described [22-24]. Although it has generally been more practical to assess only the original four taste qualities due to the complexity of the umami taste system, routine clinical evaluation of gustatory function sometimes includes umami.
Olfaction — Effective olfaction involves odorant stimuli appropriately stimulating smell receptors of the olfactory mucosa, with accurate neural transmission to and processing of the information by the olfactory bulb, the olfactory cortex, and components of the limbic system (figure 2).
The nasal cavity is lined with respiratory epithelium, with the epithelial surface covered by a mucous layer secreted by the submucosal Bowman's glands [25]. Within this mucous layer are immunoglobulins (IgA and IgM), lactoferrin, and lysozyme; these agents help prevent pathogens from gaining intracranial entry [26]. Also within the mucous are odorant-binding proteins that facilitate the binding and transport of odorants to receptors; these are also believed to bind and remove odorants once activation has occurred [14].
Olfactory receptor cells, neurons located within the olfactory mucosa, are located along the superior and middle turbinates and upper part of the nasal septum [27]. These flask-shaped neurons terminate in a dilated knob from which cilia extend into the overlying mucus [26]. Odorants bind to and activate the receptors on the cilia. The axons of the olfactory receptor cells (approximately 6 to 10 million in each nasal cavity) travel up through the cribriform plate of the ethmoid bone and terminate in the glomeruli of the olfactory bulb, where they synapse with olfactory nerve cells. Bundles of olfactory nerve axons project via olfactory tracts to each olfactory nucleus, orbitofrontal cortex, thalamus, hypothalamus, and amygdala.
Olfactory neurons are directly exposed to the external environment, with the potential for injury from infection, inflammation, and toxic chemical agents. Although new olfactory neurons are continuously formed during adulthood with the ability to replace those lost through injury [28], there is evidence that the overall number of olfactory neurons decreases with age [29]. In addition to cell loss from injury, there is regular turnover of olfactory receptor neurons via apoptosis, a programmed process which leads to cell death. Chronic inflammation may increase the degree of apoptosis. For example, increased levels of caspase 3, the dominant enzyme in the apoptotic pathway, have been identified in olfactory epithelial cells in patients with paranasal sinus disease [30].
Flavor perception is multisensory — Flavor perception is a complex sensory experience encompassing more than only the chemosensation of taste. It is a multisensory phenomenon involving gustatory, olfactory, tactile, and even visual information. While eating, olfactory information can reach the olfactory cleft via the nose from the external environment (orthonasal smell) or via the mouth through the oropharynx (retronasal smell) [31]. Studies suggest that odors are perceived differently when presented via the orthonasal versus retronasal route [32]. The retronasal route is an important part of our ability to appreciate the flavor of foods [33] and likely reflects the evolutionary role of olfaction in food identification [34]. The aroma of food and beverages is the most important contributor to flavor, and olfactory dysfunction is often misidentified by patients as a problem with taste [35].
ETIOLOGIES OF TASTE AND OLFACTORY DYSFUNCTION
Taste dysfunction — Ageusia is rarely encountered due to the redundancy of taste neuroanatomy; dysgeusia and hypogeusia are much more common [36]. Since gustatory function is dependent upon the interaction of tastants with saliva, carrier proteins, and taste receptors, dysgeusia and hypogeusia can result when there is dysfunction of one or more of these systems (figure 1 and table 1).
●Infectious and inflammatory causes – Dysgeusia and hypogeusia can result from inflammation anywhere in the oropharynx, including infections and inflammatory conditions of the teeth, larynx, pharynx, tongue, taste buds, and salivary glands.
•Infectious causes:
-Gingivitis, oropharyngeal candidiasis (thrush), and dental caries may cause dysgeusia. Infections in the oropharynx may inhibit normal blood flow to the tongue and taste buds, reducing the efficacy of normal gustatory function. There may be a bidirectional relationship between altered taste and certain dental infections; genetic polymorphisms in taste receptor proteins, which alter taste sensitivity and preferences for sweet tastes, may predispose to the development of dental caries by causing an increase in sugary food consumption [37]. (See "Oropharyngeal candidiasis in adults", section on 'Signs and symptoms' and "Epidemiology, pathogenesis, and clinical manifestations of odontogenic infections", section on 'Gingivitis'.)
-Disturbances of taste perception, including hypogeusia and dysgeusia, can occur in the setting of influenza-like illnesses and may be due to disruption of taste pores and infiltration of the lamina propria by inflammatory cells [38].
-Many patients with coronavirus disease 2019 (COVID-19) experience the sudden onset of ageusia and/or anosmia as isolated symptoms, presenting prior to the development of other symptoms, or at some point during the course of their illness [39-43]. Disturbances of taste and smell occur in 63 to 85 percent of patients, with most developing symptoms within four days of illness onset [44-47]. (See 'Olfactory dysfunction' below and "COVID-19: Clinical features", section on 'Initial presentation'.)
•Inflammatory causes:
-Inflammation of the salivary glands from Sjögren's syndrome, other autoimmune disorders, or systemic radioiodine therapy can impair gland function and contribute to hypogeusia or dysgeusia [48,49]. Furthermore, xerostomia (dry mouth) may increase the risk of dental caries [50]. (See "Clinical manifestations of Sjögren's disease: Exocrine gland disease" and "Salivary gland swelling: Evaluation and diagnostic approach", section on 'Immune-mediated sialadenitis' and "Salivary gland swelling: Evaluation and diagnostic approach", section on 'Inflammatory causes'.)
-Inflammation of the tongue (glossitis) may cause closure of taste pores through which tastants access the taste buds [51]. In addition, vitamin B-12 deficiency can cause atrophic glossitis with a loss of most or all of the lingual papillae and taste buds; this is reversible with effective B-12 supplementation. (See "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency", section on 'Clinical presentation'.)
-Radiation therapy (or accidental exposure to ionizing radiation) to the head and neck can cause taste impairment, via direct taste cell injury, and damage to the taste buds and salivary glands [52]. Decreased salivary production may predispose to oropharyngeal infections which can further impair gustatory function [53]. The extent of taste impairment largely correlates with the radiation dose to the tongue. Taste cells are continuously replaced, so taste impairment recovers over time after completion of radiation therapy, although not always completely [52]. (See "Treatment of stage I and II (early) head and neck cancer: The oral cavity", section on 'Radiation therapy' and "Oral health in cancer survivors", section on 'Chronic salivary gland hypofunction'.)
-Reflux of gastric acid, particularly laryngopharyngeal reflux, may cause hypogeusia or dysgeusia [54-56] and also impact taste sensitivities and preferences [57].
●Drugs – A number of drugs may affect gustatory function, with mechanisms of action including direct tastant activity and effects on saliva, taste receptor cells, peripheral nerves, the central nervous system (CNS), and zinc levels as well as other unknown effects (table 2) [8,58-69]. (See "Oral toxicity associated with systemic anticancer therapy", section on 'Alterations in taste and smell' and "Pathogenesis, clinical features, and assessment of cancer cachexia", section on 'Reduced dietary intake or absorption'.)
Examples of medication-related taste complaints and specific medications associated with them include:
•Dysgeusia – Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), dipyridamole, nitroglycerin, vandetanib, vismodegib
-Bitter dysgeusia – Acetazolamide, methylphenidate
-Metallic dysgeusia – Allopurinol, baclofen, beta-lactam antibiotics (eg, amoxicillin, cephalexin), clarithromycin, metronidazole, ethambutol, flurazepam, interferon-gamma, levamisole, lithium, tetracycline, tocainide, lidocaine (intravenous)
•Hypogeusia (to one or more tastants) or ageusia – ACE inhibitors, ARBs, amiloride, amphotericin B, amrinone, bleomycin, carbamazepine, carboplatin, cisplatin, chlorhexidine mouth rinse, dicyclomine, diltiazem, etidronate, hydrochlorothiazide, hyoscyamine, isotretinoin, levodopa, lovastatin, methimazole, nifedipine, ofloxacin, spironolactone, sulfasalazine, terbinafine, triazolam
●Exposure to chemicals, toxins, and metals – Exposure to chemicals, toxins, and metals typically causes dysgeusia and phantogeusia; ageusia is rare.
•Acute exposure to organophosphates can impair gustatory function by altering taste bud morphology [70] and by interfering with peripheral and CNS signal transmission [60]. Pesticides can reach taste receptors through air, water, or food.
•Metals and metalloids, including mercury, copper, zinc, chromium, arsenic, and lead may cause taste alterations. As examples, in a case series of seven adults with occupational acute lead poisoning, all affected individuals described a sweet metallic taste [71]. In addition, metal-fume fever (occupational exposure to zinc oxide fumes in brass and steel foundry workers and welders) is characterized by a sweet, metallic taste in addition to respiratory and systemic complaints [72]. Dental patients who have appliances or dental work with inorganic mercury containing amalgam (dentures, fillings) have also complained of metallic dysgeusia [73]. (See "Lead exposure, toxicity, and poisoning in adults".)
•Acute solvent exposure has been associated with transient dysgeusia [74,75].
●Nerve damage – Complete ageusia due to nerve damage (eg, trauma, surgery, radiation, cranial nerve VII [Bell's] palsy) is rare due to the redundancy of the nerves involved in taste function; marked hypogeusia is also unusual in the absence of severe central neurologic damage. For example, in a study of patients with a history of head trauma, 19 percent experienced dysgeusia, but only 2 percent complained of complete taste loss [76]. (See "Evaluation and management of middle ear trauma", section on 'Adjacent structures' and "Bell's palsy: Pathogenesis, clinical features, and diagnosis in adults", section on 'Clinical features'.)
Mild hypogeusia, however, is more likely in the setting of nerve damage and is related to localized taste impairment. For example, injury to the chorda tympani nerve, which may occasionally occur with middle ear surgery, may cause taste loss or dysgeusia affecting the ipsilateral anterior two-thirds of the tongue [77]. Additionally, the chorda tympani and lingual nerves also can be damaged during third molar extractions [78,79]. Bronchoscopy, laryngoscopy, or tonsillectomy can cause taste dysfunction due to injury of the lingual branch of the glossopharyngeal nerve [80]. (See "Tonsillectomy in adults: Techniques and perioperative issues", section on 'Other complaints and complications'.)
●Vitamin and mineral deficiencies – In addition to vitamin B-12 deficiency which can impair taste function by causing atrophic glossitis, zinc deficiency is associated with dysgeusia and hypogeusia [81,82]. Patients with taste disturbances and who are at risk for zinc deficiency (eg, patients with malnutrition, malabsorption, Crohn disease, chronic liver disease, diabetes mellitus, sickle cell disease, end-stage kidney disease [ESKD], and those on medications that increase urinary losses of zinc [eg, thiazide diuretics, ACE inhibitors, ARBs]) should have a zinc level checked [83]. (See "Overview of dietary trace elements", section on 'Deficiency' and "Vitamin and mineral deficiencies in inflammatory bowel disease", section on 'Zinc' and "Hepatic manifestations of sickle cell disease", section on 'Zinc deficiency'.)
●Metabolic and endocrine disorders – Several common metabolic and endocrine disorders, including ESKD, hypothyroidism, and diabetes mellitus (types I and II) are associated with dysgeusia [60].
•The taste disturbances associated with ESKD are multifactorial [84,85]. ESKD can be associated with a reduction in the number of fungiform taste buds [86] and, among patients with ESKD on hemodialysis, reduced salivary production and altered salivary composition [87]. Hemodialysis patients may also have zinc deficiency [88].
•Patients with diabetes may experience different types of taste dysfunction, with dysgeusia and hypogeusia the most common. Among patients with diabetes, hypogeusia to sweet taste can occur, with a higher taste threshold to sweet tastes compared with patients without diabetes [89]. In addition, diabetic neuropathy may contribute to dysgeusia [90].
•Hypothyroidism may be associated with dysgeusia. As an example, in a series of 18 patients with uncorrected primary hypothyroidism, half felt that their sense of taste was diminished or altered, but upon formal testing, over 80 percent were found to have hypogeusia to one or more taste stimuli [91]. The etiology of taste disturbance in hypothyroidism is likely multifactorial and may be related to altered saliva production or mucous membrane or taste bud structure. The taste disturbance, however, is reversible with normalization of thyroid function [92].
●Neurologic disorders – Several neurologic disorders may be associated with hypogeusia or dysgeusia, including Alzheimer disease [93], Guillain-Barré syndrome [94], Parkinson disease [95], and multiple sclerosis [96,97].
●Burning mouth syndrome – Burning mouth syndrome, a condition of unknown etiology occurring primarily in postmenopausal women, is characterized by a chronic, fluctuating, burning intraoral pain without objective signs of inflammation and can be associated with taste disturbance [98,99]. Although the precise pathophysiologic mechanism is unknown, it is believed to be due to dysfunction of the peripheral and/or CNS. (See "Overview of craniofacial pain", section on 'Burning mouth syndrome'.)
●Tobacco – Use of tobacco products (smoked and chewed) may cause reversible hypogeusia [100,101].
●Aging – Diminished taste perception occurs with advancing age, although olfactory function is typically more affected with aging [102]. Taste detection and recognition thresholds are higher in older individuals, with reduced sensitivity to sweet, sour, salty, and bitter tastes [103]. Some believe that a decline in the number of taste buds and taste receptor cells is responsible for the taste impairment observed with aging, while others credit the change to alterations in taste cell membranes [104]. In addition, changes in salivary chemical composition and an overall decrease in saliva production in response to gustatory stimuli are likely contributors to the hypogeusia seen with aging [18].
Hypogeusia can result in an increased consumption of sugar or salt, possibly putting vulnerable patients at risk (eg, those with diabetes or congestive heart failure) if sugar and salt are consumed in greater amounts to satisfy taste needs [105]. In addition, a diminished sense of taste may contribute to anorexia among some older adults, making it difficult to meet nutritional requirements [51]. (See "Normal aging", section on 'Taste and smell'.)
Olfactory dysfunction — Impaired olfaction is a frequent patient complaint, with hyposmia and dysosmia most often encountered; anosmia is less commonly seen.
Among patients presenting with olfactory dysfunction, nasal and paranasal sinus disease (chronic rhinosinusitis with or without nasal polyps) and post-viral upper respiratory infections are the most commonly identified causes [36,106]. Head (including facial) trauma is another frequent cause [107]. Other etiologies include aging, neurodegenerative conditions (eg, Alzheimer disease, Parkinson disease), structural brain disease (eg, Kallman syndrome, intracranial neoplasm, ischemia), medications, or drugs (table 3 and table 4). (See "Isolated gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)", section on 'Anosmic form of IHH (Kallmann syndrome [KS])' and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'Signs and symptoms'.)
●Nasal and paranasal sinus disease – Nasal and paranasal sinus disease, primarily due to rhinosinusitis and nasal polyps but also from allergic rhinitis, are the most common causes of olfactory dysfunction and/or anosmia. These conditions can interfere with olfaction through inflammation of the mucosa as well as overt obstruction of the nasal passages. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)
Rare causes of nasal and paranasal sinus disease, such as olfactory neuroblastoma (esthesioneuroblastoma), a malignant tumor of the olfactory epithelium, may also impair olfaction. (See "Olfactory neuroblastoma (esthesioneuroblastoma)", section on 'Clinical manifestations'.)
●Infectious and postinfectious – Temporary hyposmia or anosmia in the setting of an acute viral upper respiratory infection is common due to local mucosal effects, but in 6 to 13 percent of patients, the olfactory dysfunction may persist after resolution of the acute infection [108]. Viral upper respiratory infections can damage peripheral olfactory receptors and central olfactory pathways [109,110], typically causing hyposmia [107]. Viruses may affect central olfactory pathways differently, contributing to the varying rates and degree of postinfectious olfactory dysfunction [108,111]. (See "The common cold in adults: Diagnosis and clinical features", section on 'Acute rhinosinusitis'.)
Postinfectious olfactory dysfunction generally improves, although for many, some degree of dysfunction may persist. In an observational study of 63 patients with post-viral upper respiratory olfactory dysfunction, 86 percent of patients reported subjective recovery after two years, but only 32 percent reported normosmia [112].
In addition, many patients with COVID-19 may experience the sudden onset of anosmia and/or ageusia as isolated symptoms, presenting prior to the development of other symptoms or at some point during the course of their illness [39-43,113]. In one study of 790 patients with confirmed SARS-CoV-2 infection, 79 percent experienced loss of smell; 83 percent of those had complete olfactory loss and 17 percent had partial loss [44]. 49 percent of affected patients had complete olfactory recovery, with most recovering within 10 days. In observational studies, olfactory recovery rates ranged from 53 to 89 percent [44-47].
Some patients, however, may have persistent smell loss; in a study including 300 post COVID-19 patients with olfactory loss, 27 percent experienced persistent olfactory dysfunction at six months [45]. In another study including 170 subjects with previous COVID-19, 26.5 percent had persistent olfactory dysfunction at one year (anosmia in 4.7 percent and hyposmia in 21.8 percent) [114].
The explanation for varying outcomes may be due to differing etiologies, from transient losses due to an obstructive phenomenon with local inflammation, which can recover after two to six weeks, to more persistent loss due to damage to olfactory epithelium or a disruption in olfactory processing networks [115]. (See "COVID-19: Clinical features", section on 'Initial presentation'.)
●Posttraumatic – Head trauma, including maxillofacial trauma with associated fracture, is a common cause of smell impairment [116]. Although any type of posttraumatic olfactory dysfunction may occur, hyposmia and anosmia are most frequently seen.
Mechanisms by which trauma can affect olfaction include [117,118]:
•Damage to the nasal passages and/or paranasal sinuses from trauma (eg, nasal bone fracture, septal deviation, mucosal hemorrhage and edema), or surgery (eg, septal and sinus surgery, including endonasal transsphenoidal procedures) with mechanical obstruction to odorants or injury to the olfactory neuroepithelium [119,120]
•Shearing or disruption of the primary olfactory axons as they travel through the cribriform plate [121]
•Contusion or destruction of the olfactory bulb [122,123]
•Contusion or destruction of the olfactory cortex [124,125]
Hyposmia can be seen among many patients with even mild traumatic brain injury (TBI), and the likelihood of olfactory dysfunction increases with the frequency and severity of prior injuries [126,127]. As an example, in a prospective study of patients with TBI, increasing severity of brain injury severity was associated with an increased likelihood of olfactory dysfunction; the prevalence increased from 18 percent among those with grade I (mild) TBI to 57 percent among those with grades II and III (moderate to severe) TBI [128]. (See "Traumatic brain injury: Epidemiology, classification, and pathophysiology", section on 'Clinical severity scores'.)
Olfactory neurons have regenerative capabilities and there may be recovery of olfactory function after trauma [129]. However, the likelihood and degree of olfactory recovery most closely correlates with the degree of initial posttraumatic smell impairment [130]. In addition, any improvement in olfactory function is more likely to occur early (within the first several months) after the traumatic event [131]; clinically meaningful improvement in smell function after a period of years is not expected [117].
The type and degree of olfactory dysfunction may be associated with the extent of damage to different neural structures, including the olfactory bulb and the olfactory cortex. In a retrospective study including 25 patients with trauma-induced olfactory impairment, greater olfactory bulb volume loss was associated with a greater degree of olfactory dysfunction (anosmia, hyposmia, and parosmia), while more extensive cortical (frontal and temporal lobe) damage was more specifically associated with retronasal olfactory impairment and parosmia [122].
●Central nervous system abnormalities (non-traumatic) – Other abnormalities of the CNS, including neurodegenerative conditions (eg, Alzheimer disease, Parkinson disease, dementia with Lewy bodies) or ischemia (eg, infarct, hemorrhage, edema with compression) may cause injury to olfactory brain centers [132-134].
•In Alzheimer disease, olfactory function is impaired, including defective odor identification and discrimination, and altered detection thresholds. Early in the onset of disease, disturbed odor identification can often precede cognitive symptoms [135]. With progression of disease, odor detection typically becomes markedly impaired [136,137]. In Alzheimer disease, olfactory pathways demonstrate pathologic abnormalities including neuritic plaques and decreased acetyl cholinesterase levels [132,135,136]. Among individuals with a genetic abnormality associated with Alzheimer disease, olfactory dysfunction may be a marker for future cognitive decline [138]. (See "Epidemiology, pathology, and pathogenesis of Alzheimer disease", section on 'Pathology' and "Clinical features and diagnosis of Alzheimer disease", section on 'Olfactory dysfunction' and "Epidemiology, pathology, and pathogenesis of Alzheimer disease", section on 'Genetic risk factors'.)
Parkinson disease and dementia with Lewy bodies are also associated with olfactory impairment [139-141]. In Parkinson disease, disturbed odor identification and discrimination, altered detection thresholds, and phantosmia can be seen in the early stages of disease. As an example, in a prospective study including almost 2300 Hawaiian men aged 71 to 95 years, greater olfactory impairment was associated with an increased incidence of developing Parkinson disease over the subsequent four years (odds ratio [OR] 5.2, 95% CI 1.5-25.6) [142].
In patients with Parkinson disease and dementia with Lewy bodies, the olfactory bulbs typically reveal Lewy bodies in the neurons of the anterior olfactory nucleus and mitral cells with subsequent neuronal loss [143]. (See "Clinical manifestations of Parkinson disease", section on 'Olfactory dysfunction' and "Clinical features and diagnosis of dementia with Lewy bodies", section on 'Hyposmia' and "Clinical features and diagnosis of dementia with Lewy bodies", section on 'Hallucinations in other modalities'.)
Other neurodegenerative conditions such as pure autonomic failure (PAF) and multiple system atrophy (MSA) may be associated with olfactory impairment [144]. (See "Mechanisms, causes, and evaluation of orthostatic hypotension", section on 'Neurodegenerative disorders' and "Multiple system atrophy: Clinical features and diagnosis".)
•Ischemia to any component of the central olfactory pathway, including the olfactory bulb, cortex, or limbic system, may cause impairment (transient or permanent) of olfactory function. As an example, in a case series of 19 patients with acute ischemic stroke, thalamic hypoperfusion was associated with reduced odor recognition and identification [145].
Persistent anosmia may result from subarachnoid hemorrhage (SAH); it occurs more commonly following aneurysmal than nonaneurysmal SAH (15 to 30 percent versus 5 percent respectively) [146,147]. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Neurologic morbidity'.)
•Kallmann syndrome is a hyposmic or anosmic form of idiopathic hypogonadotropic hypogonadism (IHH) [148]. It is associated with one of several genetic abnormalities causing impaired embryonic migration of particular cells to the hypothalamus and olfactory bulb. (See "Isolated gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)", section on 'Anosmic form of IHH (Kallmann syndrome [KS])' and "Physiology of gonadotropin-releasing hormone", section on 'Embryonic migration'.)
•Other CNS conditions that may be associated with olfactory disturbances include idiopathic intracranial hypertension (pseudotumor cerebri) [149-152], multiple sclerosis [153], malignancy [154], and meningiomas, particularly those located in the olfactory groove [155]. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis" and "Clinical presentation, course, and prognosis of multiple sclerosis in adults" and "Epidemiology, pathology, clinical features, and diagnosis of meningioma", section on 'Focal findings'.)
●Exposure to chemicals, toxins, and metals – Olfactory receptors are directly exposed to the environment, and exposure to chemicals, toxins, and metals may cause olfactory dysfunction [156].
Occupational exposure to methacrylate vapors, ammonia, benzene, cadmium dust, chromate, formaldehyde, hydrogen sulfide, nickel dust, solvents, and sulfuric acid are known to cause olfactory impairment [157]. As an example, in a study evaluating olfactory function in bridge welders exposed to welding fumes (a mixture of metallic oxides, fluorides, and silicates), olfaction was impaired compared with control subjects [158].
Environmental exposure to these chemicals, in addition to other agents such as ozone, lead, and manganese, may also impair olfaction [159]. Exposure via ambient air pollution has acute and cumulative effects on olfaction, with acute neuroepithelial cytotoxic effects in addition to permanent neurotoxic effects on the olfactory bulb [160].
●Medications and drugs – Medications and drugs may cause olfactory impairment, although the effect is generally more limited than on taste function.
Beta blockers, calcium channel blockers, and ACE inhibitors can lead to olfactory abnormalities [161]. Intranasal zinc preparations have been associated with the development of hyposmia and anosmia [162].
Intranasal cocaine use can damage the olfactory neuroepithelium as well as central olfactory neurons [163], although in many users olfaction is unaffected [164].
●Tobacco use – Tobacco smoking may cause olfactory impairment [165,166]; olfactory function generally improves over time following smoking cessation [167].
●Endocrine disorders – Common endocrine disorders, such as hypothyroidism and diabetes mellitus, may be associated with olfactory dysfunction [91,168].
•Diabetes mellitus (types I and II) may be associated with disturbances in smell, including hyposmia, anosmia, and parosmia. As an example, in a study including over 3000 diabetic adults ≥40 years, individuals with diabetes were more likely to have phantosmia than those without diabetes (OR 2.42, 95% CI 1.16-5.06) [168]. Furthermore, among those with diabetes, individuals on insulin treatment had a higher risk of severe hyposmia or anosmia than those on no diabetes pharmacotherapy (OR 2.86, 95% CI 1.28-6.4).
•Hypothyroidism is associated with hyposmia, and the decreased sensitivity to smell may be due to a diminished olfactory cortical responses to odor stimuli [169]. Effective treatment with thyroid hormone can improve olfactory function in hypothyroid patients [92].
●Aging – Olfactory function decreases with normal aging, with several processes contributing [170]. With advancing age, there is a loss of olfactory epithelial surface area and a decrease in the density of innervation within the nasal and sinus mucous membranes [171]. In addition, the olfactory bulb undergoes degenerative changes with normal aging that results in a loss in the total number of neurons [172]. It is estimated that the young adult olfactory bulb contains approximately 60,000 mitral cells (olfactory neurons), with only about 14,500 neurons remaining by age 95 years [173]. Finally, neurofibrillary tangles and amyloid deposits are common in the olfactory bulbs of healthy older adults [136]. (See "Normal aging", section on 'Taste and smell' and "Normal aging", section on 'Anatomical and physiologic changes'.)
SUMMARY AND RECOMMENDATIONS
●Overview – Taste and smell disorders are common in adults and may be attributable to a number of causes, including metabolic and endocrine abnormalities, neurologic disorders, inflammatory conditions of the nasal passages and paranasal sinuses, head trauma and surgery, infections, chemical exposures, medication side effects, and even normal aging (table 1 and table 2 and table 3 and table 4). Impaired taste and olfaction can negatively impact flavor perception, decreasing the quality of life and interfering with adequate nutritional intake. (See 'Introduction' above.)
●Definitions – Normogeusia and normosmia describe normal taste and smell functions, respectively. Definitions for abnormalities of taste and olfaction include (see 'Definitions' above):
•Hypogeusia – Diminished taste function to one or more specific tastants
•Ageusia – Absent taste function
•Dysgeusia – Altered (sweet, sour, salty, bitter, or metallic) perception of taste in response to a tastant stimulus
•Aliageusia – Taste disturbance in which a typically pleasant-tasting food or drink tastes unpleasant
•Phantogeusia – Unpleasant taste due to a gustatory hallucination (in the absence of any stimulus)
•Hyposmia – Diminished smell function
•Anosmia – Absent smell function
•Parosmia – Abhorrent odor perception either with an odorant stimulus (troposmia or smell distortion) or without an odorant stimulus (phantosmia)
•Dysosmia – A general term describing distortion of smell sensations
●Anatomy and physiology – Taste and olfaction have discrete physiology and anatomy, with each dependent upon unique receptors and neural pathways (figure 1 and figure 2). The perception of flavor is multifactorial, relying upon efferent taste and olfactory input in addition to other sensory information. (See 'Anatomy and physiology of taste, olfaction, and flavor perception' above.)
●Taste dysfunction: Etiologies – Ageusia is rarely encountered; dysgeusia and hypogeusia are much more common. Taste dysfunction may result from systemic viral infections as well as from inflammation anywhere in the oropharynx, including infections and inflammatory conditions of the larynx, pharynx, tongue, taste buds, and salivary glands. A number of drugs and medications may affect gustatory function, with mechanisms of action including direct tastant activity and effects on saliva, taste receptor cells, peripheral nerves, the central nervous system (CNS), and zinc levels. Exposure to chemicals, toxins, and metals typically causes dysgeusia and phantogeusia; ageusia is rare (table 2).
Complete ageusia due to nerve damage is rare due to the redundancy in the nerves involved in taste function; marked hypogeusia is also unusual in the absence of severe central neurologic damage. Mild hypogeusia, however, is more likely in the setting of nerve damage due to localized taste impairment.
B-12 deficiency can impair taste function by causing atrophic glossitis; zinc deficiency is associated with dysgeusia and hypogeusia. Several common metabolic and endocrine disorders, including end-stage kidney disease (ESKD), hypothyroidism, and diabetes mellitus (types I and II) are associated with dysgeusia (table 1). Diminished taste perception occurs with advancing age. (See 'Taste dysfunction' above.)
●Olfactory dysfunction: Etiologies - Impaired olfactory function is a frequent patient complaint, with hyposmia and dysosmia most typically encountered. Anosmia is less often seen in the adult population. Among patients presenting with olfactory dysfunction, nasal and paranasal sinus disease (chronic rhinosinusitis with or without nasal polyps) and post-viral upper respiratory infections are the most commonly identified causes. Head (including facial) trauma is another frequent cause. Other etiologies include acute coronavirus disease 19 (COVID-19), normal aging, neurodegenerative conditions (eg, Alzheimer disease, Parkinson disease), structural brain disease (eg, Kallman syndrome, intracranial neoplasm, ischemia), medications, or drugs (table 3 and table 4). (See 'Olfactory dysfunction' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Norman Mann, MD, who contributed to an earlier version of this topic review.
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