- Email: [email protected]
The Impact of Aging and Medical Status on Dysgeusia
Accepted Manuscript The impact of aging and medical status on dysguesia Quratulain Syed, M.D., Kevin T. Hendler, DDS, FASGD, Kenneth Koncilja, M.D. PII:
S0002-9343(16)30177-2
DOI:
10.1016/j.amjmed.2016.02.003
Reference:
AJM 13380
To appear in:
The American Journal of Medicine
Received Date: 27 November 2015 Revised Date:
26 January 2016
Accepted Date: 1 February 2016
Please cite this article as: Syed Q, Hendler KT, Koncilja K, The impact of aging and medical status on dysguesia, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.02.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title Page: Title: The impact of aging and medical status on dysguesia
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Authors: Quratulain Syed, M.D.
Emory University School of Medicine,
Tel: 404.778.1630 [email protected]
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49 Jesse Hill Jr. Drive, Atlanta, GA 30303
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Assistant Professor of Medicine,
Financial Disclosures and conflicts of interest: none
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Kevin T Hendler, DDS, FASGD
Diplomate, American Board of Special Care Dentistry Associate Professor, Emory University School of Medicine
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Director, Geriatric Dentistry, Ina T Allen Dental Center, Emory Healthcare 1841 Clifton Road, Atlanta, GA 30329
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404 728 6432
[email protected]
Financial Disclosures and conflicts of interest: none
Kenneth Koncilja, M.D. Cleveland Clinic,
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9500 Euclid Avenue X10, Cleveland, OH 44195 [email protected]
Corresponding author: Quratulain Syed, M.D. Assistant Professor of Medicine, Division of General Medicine and Geriatrics,
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Emory University School of Medicine,
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Financial Disclosures and conflicts of interest: none
49 Jesse Hill Jr. Drive, Atlanta, GA 30303 Tel: 404.778.1630 Fax: 404.778.1602
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[email protected]
Additional authors disclosure: All authors had access to the data and a role in writing
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the manuscript.
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Article type: clinical narrative review article
Key words: dysgeusia, weight loss, hospitalized elderly, long term care, oral care, polypharmacy
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Manuscript:
Clinical Significance/Key Points
residing in long term care facilities. •
Dysgeusia can impact a patient’s enjoyment of food, overall nutritional status and management of chronic diseases.
•
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Dysguesia is fairly prevalent in older adults, esp. those admitted in hospitals or
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•
Review of medications and attention to oral health should be prioritized in
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patients presenting with dysgeusia.
Abstract
Disorders of taste and/or smell can cause an aversion to food in a sick patient and
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therefore affect his/her ability to maintain optimal nutrition1. This can lead to a reduced level of strength, muscle mass, function, and quality of life. Additionally, reduced ability to differentiate between various intensities or concentrations of a tastant can result in
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increased intake of salt and sugar and exacerbation of chronic diseases such as heart failure and diabetes2.
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These implications can be heightened in the elderly who are particularly frail and are challenged by polypharmacy and multiple comorbid conditions. In this article, we will review the prevalence, etiology and management of taste disorders. Additionally, we will review the association between taste and smell disorders and how disorders of smell can affect perception of taste.
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Clinical Scenario Ms. Edwards is an eighty nine year old female nursing home resident admitted to an inpatient medicine service for failure to thrive, severe malnutrition, loss of appetite and a
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25 pound weight loss in the past six months. Past medical history is significant for
osteoporosis, congestive heart failure, chronic renal insufficiency and hypothyroidism. She has been hospitalized twice during the past 6 months for exacerbation of heart
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failure, with resultant adjustment of her heart failure medication regimen. She notes a
persistent loss of appetite and lack of taste in her food for the past six months, preventing
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her from enjoying her food. She denies any difficulty swallowing, nausea, vomiting, or abdominal pain on eating. She also denies being depressed. Basic blood work indicated acute renal insufficiency due to dehydration, which was corrected with intra venous fluids. Other blood work including electrolytes, liver function and thyroid function labs
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were unremarkable. She underwent an upper gastrointestinal endoscopy and a colonoscopy which failed to show any ulcers or evidence of malignancy.
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Terminology and Definitions
Taste disorders (dysgeusias) can be classified into qualitative and quantitative disorders.
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The qualitative disorders include parageusias (inadequate or wrong taste perception elicited by a stimulus) and phantogeusias (presence of a persistent, unpleasant taste in the absence of any stimulus). The quantitative disorders include ageusia (a complete loss of the ability to taste), hypogeusia (a partial loss of the ability to taste), and hypergeusia (enhanced gustatory sensitivity)3. Burning mouth syndrome (BMS) also referred to as
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glossodynia or somatodynia, is a sensation of spontaneous, continuous burning pain felt in the tongue or oral mucosa, commonly seen in post-menopausal women. Impairment in sense of smell is called dysosmia and complete loss of sense of smell is
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called anosmia.
Prevalence
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The National Health and Nutrition Examination Survey (NHANES) 2011-2012 reported that more than 5% of the over 142 million US respondents experienced taste disorders
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and more than 10% experienced smell disorder in the past 12 months. Gender was not associated with the prevalence of either disorder, but increasing age was associated with increasing prevalence of both taste and smell disorders 4. Additionally, taste disorders are more prevalent in hospitalized and institutionalized older adults compared to those living
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in the community5,6. Glazer et al reported taste disturbance in 13.9% of institutionalized individuals compared to 3.2% of community dwelling individuals7. Aging can affect gustatory function as observed by increasing of electrogustometry (EGM) thresholds and
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Anatomy
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reduction in density of fungiform papillae 8.
Gustatory receptor cells are present in the taste buds on the dorsal and lateral surfaces of the tongue, the soft palate, uvula, larynx, pharynx, epiglottis, and esophagus. These receptor cells are innervated by afferent neurons and are able to regenerate with a halflife of about 15 days. Transduction of the five taste stimuli, acid, salt, bitter, sweet, and umami (a pleasant savoury taste imparted by glutamate), occurs by different chemical
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transmission systems. Taste sensations are transported via 3 cranial nerves; Cranial Nerve VII innervates the anterior third of the tongue and the palate, Cranial Nerve IX innervates the back of the tongue, Cranial Nerve X innervates the oropharynx and the pharyngeal
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portion of the epiglottis. Additional taste receptors are found in the small intestine. The Trigeminal nerve (Cranial Nerve V) is also involved in the transfer of sensations such as the temperature, texture and spiciness of food. The brain stem, thalamus, and the anterior
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insula play a key role in the processing of the taste information by the central nervous system. Due to involvement of multiple nerve tracts, it's rather difficult to completely
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lose the sense of taste.
Olfaction on the other hand, relies only on the olfactory nerve, and its axons pass through the cribriform plate of the ethmoid bone prior to dissemination on the surface of the olfactory bulb. This makes it highly vulnerable to injury during head trauma. In this
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Etiology
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situation, a complete loss of sense of smell is more common.
Impairment in Sense of Olfaction and its effect on taste:
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Since the taste sensations are conducted by three major nerves, a complete loss of taste (ageusia) is very rare and only occurs in 3 % of all patients with dysgeusia3. Among those patients presenting for evaluation of loss of taste and smell, 70% report loss of smell alone or in addition to loss of taste. Less than 10% report an isolated loss of taste while only 4% have a solitary measurable loss in gustation3,9. Therefore, olfactory symptoms
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should be explored and olfactory function be evaluated in patients presenting with a complaint of loss of taste. Genetic:
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In a study involving patients with phantogeusia, there was increased expression rate of some of the T2R taste receptor genes compared to controls, hinting that increased
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expression of taste receptor genes may be involved in the pathogenesis of phantogeusia10.
Post-operative:
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Middle ear surgeries with resultant transection of the chorda tympani nerve can result in gustatory impairment11. Additionally, tonsillectomies, dental procedures such as extractions and treatment of abscessed teeth, and wearing dental prostheses can contribute to phantogeusia and glossodynia 3. There have been case reports of ageusia
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after the use of laryngeal mask airways for surgery, and compression of the lingual nerve has been hypothesized as the cause. Local anesthetic injected near the inferior alveolar nerve during dental procedures has been reported to cause ipsilateral loss of taste and
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few months12.
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atrophy of fungiform papillae. However, these symptoms have been noted to resolve in a
Medications:
Numerous medicines are excreted in saliva by carrier-mediated transport or passive diffusion13. They can affect sense of taste by various mechanisms including drug-receptor interaction, disturbance of action potential propagation in cell membranes of afferent and efferent neurons, and alteration of the neurotransmitter function. Additionally, limiting
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the access of taste chemicals to sensing receptors due to mucosal dryness, closing of taste pores, or altering the constituents of mucous or saliva can also impact the sense of taste14. A review of the Italian national database of spontaneous adverse drug reactions (ADR)
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(Agenzia Italiana del Farmaco) from 1988-2008 showed that taste alteration alone was reported in 75% of cases of ADRs and both taste and smell impairment were noted in
13% of ADRs. Macrolides, anti-mycotics, fluoroquinolones, protein kinase inhibitors,
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angiotensin converting enzyme (ACE) inhibitors, HMG-CoA reductase inhibitors
(statins), and proton pump inhibitors (PPI) were the leading culprits14. Resolution of
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symptoms varied, with improvement reported within days to a few months after discontinuation of the offending medicine.
Anti-retroviral medications have been associated with dysgeusia in HIV patients15. Chemotherapeutic drugs used for treatment of cancers, especially 5-fluorouracil and its
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oral analogs, have also been associated with dysgeusias, with greater prevalence in the elderly16. Numerous other commonly prescribed drugs, described in table II, can
Nicotine:
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contribute to dysgeusia.
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Smoking can affect taste acuity as smokers have increased EGM thresholds and decreased vascularization and density of fungiform papillae compared to non-smokers 17.
Dementia:
Patients with mild cognitive impairment (MCI) and Alzheimer’s dementia have increased impairment in olfaction and taste compared to controls18. Alzheimer’s dementia and
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vascular dementia can affect the insula and therefore taste cognition19. Additionally, medications prescribed for management of dementias (e.g., cholinesterase inhibitors) can also contribute to taste disturbance.
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Up to 70% of patients with Parkinson’s disease (PD) experience dysosmia 20 and 9% experience dysgeusia 21. Lewy body related degeneration has been observed in
pathological examination of the olfactory bulbs in patients with Parkinson’s Disease
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which can explain the strong association between dysosmia and Parkinson’s Disease . As taste information also connects to the amygdala and hippocampus, patients with
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Parkinson’s Disease can experience dysgeusia. Additionally, patients with Parkinson’s Disease may have underlying depression, poor oral hygiene, gastrointestinal disease, and zinc deficiency which may explain dysgeusia in absence of dysosmia.
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Endocrine disorders:
Diabetes can affect gustatory function. Diabetics have been observed to have higher electrogustometric (EGM) thresholds and lower density of the fungiform papillae
control.
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compared to age matched controls22. This can affect their food choices and glycemic
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Both dysgeusia and dysosmia have been reported in patients with untreated hypothyroidism, with improvement in symptoms after treatment of the thyroid disease 23. Burning mouth syndrome (BMS) has also been reported in a few case series as a presenting feature of hypothyroidism24. Due to increased prevalence of BMS in post-menopausal women, steroid dysregulation has also been hypothesized as a possible contributor25.
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Chronic Diseases: Upper respiratory disorders are frequently associated with both taste and smell disorders.
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Upto 38% of individuals with taste problems in NHANES 2011-2012 reported
experiencing nasal congestion 4. Additionally, survey participants with a history of heart failure, heart attack, liver problems and impaired vision reported increased taste
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disturbance in the past 12 months compared to participants who didn’t have these
medical conditions. This association was valid even after adjustment for risk factors
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including head or nasal injury or sinus infections26.
Dysgeusia including metallic taste and impairment in identification and intensity of different flavors has also been observed in iIndividuals with chronic kidney disease and chronic hepatitis C. Individuals with chronic hepatitis C experience problems in
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identification and intensity of different food flavors. Numerous hypotheses have been put forth including alteration in function of affected brain cells in the taste area by the virus, and alteration in secretion of neurotransmitters involved in taste perception 27.
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Uremic state in chronic kidney disease can affect salivary flow leading to dry mouth and dysgeusia28. Additionally, medications and zinc deficiency can affect taste perception in
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patients with chronic kidney disease. The association between heart diseases and taste disturbance is usually due to concomitant renal dysfunction and adverse effects of medications.
Electrolyte and Nutritional Deficiency:
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The principle nutrient deficiency commonly associated with taste loss is zinc. A reduction in number and size of taste buds in zinc deficient animal models has been demonstrated. However, this has not been consistently verified in double-blind trials.
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Vitamin A deficiency has been associated with atrophy of taste buds in animal models and vitamin B12 deficiency can lead to atrophic glossitis resulting in loss of taste
sensation. Additionally, electrolyte disturbances including hyponatremia have been
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Oral/Dental conditions:
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reported to cause taste disturbance.
The mouth is the gateway for food into the body. Therefore, changes in the oral cavity can have an impact on taste. Older adults frequently have poor oral hygiene with increased dental caries and periodontal disease. Poor oral health may be more
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pronounced in institutionalized older adults where access to dental care may be limited and daily oral hygiene inadequate 29. Additionally, xerostomia (dry mouth) is frequently experienced by patients taking numerous medications and patients with dehydration,
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diabetes, Sjogren’s Disease and thyroid conditions. Dental caries, periodontal disease, candidiasis, stomatitis, dental-alveolar infections,
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xerostomia, tumors and mechanical trauma can lead to taste disorders in the elderly7,30. Dentures, especially those that do not fit well, can cause traumatic ulcers, stomatitis and fungal infections. Additionally, patients wearing dentures which cover the hard palate report increased taste problems31.
Malignancies:
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Chemosensory dysfunction is fairly prevalent in individuals with advanced malignancies. One study showed that 86% of individuals with advanced cancer (defined as locally
persistent bad taste in the mouth and taste distortion 32.
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recurrent or metastatic) reported some degree of chemosensory abnormality, especially
Radioactive iodine therapy (RIT) for thyroid cancers has been shown to affect salivary
increased oral pain, problems with taste and chewing33.
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flow especially from parotid glands, and high dose RIT has been associated with
Head and neck cancer patients treated with radiotherapy and/or chemotherapeutic agents
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can develop altered taste acuity, radiation induced xerostomia and dysphagia which can lead to anorexia. However, with the use of intensity-modulated radiotherapy (IMRT) in the treatment of head and neck cancer, > 80% cancer survivors reported normal or near-
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normal taste function at 3 and 5 years after IMRT34.
Mental health disorders and Epilepsy:
Dysgeusia has been reported in depressed, non-delusional patients35. Impairment in
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supra-threshold measures of sucrose taste intensities has been shown in patients with major depression compared to controls36. Gustatory (and olfactory) hallucinations can
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also be a feature of psychiatric disorders such as schizophrenia, schizoaffective disorder and bipolar disorder, or a manifestation of parietal, temporal or temporo-parietal partial seizures 37,38.
Evaluation and management of taste disorders
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It is important to screen for taste or smell disorders if your patient is experiencing appetite problems and weight loss. A proposed screening question below has been adapted from NHANES 2011-2012 survey:
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Have you experienced problems with taste or smell in the past 12 months?
A detailed history should include questions about salivary flow, problems with taste and
hygiene and ear or upper respiratory infections.
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smell, chewing problems, pain in the oral cavity, problems with teeth and dentures, dental
A loss of taste can be both regional and quality specific with different thresholds for
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different substances in different regions of the tongue, palate, and pharynx. Primary care physicians can use easily available stimuli such as sugar (sweet), citric acid (acid), sodium chloride (salty), or caffeine or quinine (bitter) to do a quick and objective taste assessment in their office. A referral to an otolaryngologist may be warranted for detailed
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evaluation.
Evaluation and management of upper respiratory infections, oral candidiasis, and basic blood work to rule out metabolic or endocrine disorders should be pursued.
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A thorough review of medications can help identify medications contributing to dysgeusia. Based on the co-morbidities and indication of the culprit medication, an
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evaluation to stop the medicine or change to an alternative medication with less taste distortion side-effects may be warranted. Taste related side effects should be discussed as part of the potential risks of prescribed medications prior to initiation of therapy. Many older adults lack private dental insurance and Medicare does not cover routine dental care. Medicaid dental coverage for adults varies by state with only about one half of the states paying for preventive dental care or restorative services39. This greatly limits
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access to dental care for low income older adults who rely on Medicaid. A dental referral for examination and treatment of oral disease should be a priority when there is a complaint of altered taste. This should also include evaluation and management of dry
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mouth. Additionally, primary care physicians should discuss the importance of good oral hygiene and the role of good oral health in the overall health of an individual.
Currently there is insufficient evidence to recommend zinc supplementation to improve
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Follow up on Ms. Edwards
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taste perception or acuity in zinc deficiency related or idiopathic dysgeusia 40.
Ms. Edwards continued to eat poorly and complain of taste impairment during her hospital stay. The inpatient medical team reviewed her medications with the help of a
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clinical pharmacist and identified numerous medicines including Lisinopril, atorvastatin, digoxin, levothyroxine, donepezil and oxybutynin which may cause taste problems. Based on clinical indication and weighing benefits and risks of treatments, the team
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decided to stop donepezil and oxybutynin. She was advised to see a dentist and her primary care physician on discharge from hospital. Her dentist diagnosed periodontal
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disease which was treated. She saw a dietician who educated her and her family on optimal nutrition and a liberalized diet. Her primary care doctor and cardiologist agreed to discontinue digoxin. Six months later, her appetite gradually improved and her weight stabilized.
This case highlights the importance of a multi-disciplinary approach to the management of taste disorders in older adults and how medical status, including oral health and
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medications, can impact taste disorders. Recognizing the causes of dysgeusia and knowing how to treat this can have a great impact on general health and overall well-
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being of patients.
Smell disturbance on history
Taste disturbance or mixed taste and smell disturbance on history
Examine oral cavity and dentition
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Review medications
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Patient complains of taste disturbance
Refer to dentist if needed
Screen for signs/symptoms of endocrine or metabolic disorders
Treat URI
Check appropriate lab work-TSH, HbA1c, LFTs
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Change offending medicines if possible
Screen for upper respiratory infections (URI)
Figure 1: schematic diagram of management of taste disorders
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Chronic medical conditions contributing to Dysgeusia Sinusitis/upper respiratory infections
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Chronic hepatitis C Chronic Kidney Disease
Heart Diseases
Cognitive disorders/dementias Parkinson’s Disease Malignancies
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Thyroid disorders, esp. hypothyroidism
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Diabetes Mellitus
candidiasis
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Dental/oral: periodontal disease, dental caries, oropharyngeal
Mental health disorders and epilepsy
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Table 1: Chronic medical conditions contributing to Dysgeusia
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Common medicines in the groups
with dysgeusia
associated with dysgeusia
Anti-microbial medicines
Macrolides, fluoroquinolones, ampicillin,
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Medication groups frequently associated
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metronidazole, tetracycline, trimethoprimsulfamethoxazole, amphotericin B,
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terbinafine and other anti-mycotic drugs
Angiotensin converting enzyme (ACE) inhibitors Anti-arrhythmic medications
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HMG-CoA reductase inhibitors (statins)
Captopril, Ramipril
Amiodarone, Procainamide Atorvastatin, Simvastatin
Proton Pump Inhibitors (PPI)
Atazanavir, Darunavir, and Ritonavir
Anti-epileptic medications
Carbamazepine, Phenytoin, Topiramate
Diuretics
Acetazolamide
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Anti-retroviral medications
Levo-dopa
Protein kinase inhibitors
Sunitinib, Erlotinib, Imatinib
Anti-cholinergic medicines
Anti-spasmodics, anti-muscarinics,
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Dopamine precursor
tricyclic anti-depressants Psychiatric medicines
Lithium, Aripiprazole
Gout medicines
Colchicine, Allopurinol
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Muscle relaxants
Baclofen
Endocrine medications
Anti-thyroid medications, Corticosteroids, Levothyroxine 5-fluorouracil, Cisplatin
Table II: Medications contributing to Dysgeusia
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Vanderwee K, Clays E, Bocquaert I, Gobert M, Folens B, Defloor T. Malnutrition and associated factors in elderly hospital patients: a Belgian cross-sectional, multi-centre study. Clinical nutrition. Aug 2010;29(4):469-476. Bennett SJ, Lane KA, Welch J, Perkins SM, Brater DC, Murray MD. Medication and dietary compliance beliefs in heart failure. West J Nurs Res. Dec 2005;27(8):977-993; discussion 994-979. Fark T, Hummel C, Hahner A, Nin T, Hummel T. Characteristics of taste disorders. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2013;270(6):1855-1860. Bhattacharyya N, Kepnes LJ. Contemporary assessment of the prevalence of smell and taste problems in adults. Laryngoscope. May 2015;125(5):1102-1106. Solemdal K, Sandvik L, Willumsen T, Mowe M. Taste ability in hospitalised older people compared with healthy, age-matched controls. Gerodontology. Mar 2014;31(1):42-48. Toffanello ED, Inelmen EM, Imoscopi A, et al. Taste loss in hospitalized multimorbid elderly subjects. Clin Interv Aging. 2013;8:167-174. Glazar I, Urek MM, Brumini G, Pezelj-Ribaric S. Oral sensorial complaints, salivary flow rate and mucosal lesions in the institutionalized elderly. Journal of oral rehabilitation. Feb 2010;37(2):93-99. Pavlidis P, Gouveris H, Anogeianaki A, Koutsonikolas D, Anogianakis G, Kekes G. Age-related changes in electrogustometry thresholds, tongue tip vascularization, density, and form of the fungiform papillae in humans. Chemical senses. Jan 2013;38(1):35-43. Deems DA, Doty RL, Settle RG, et al. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Archives of Otolaryngology--Head & Neck Surgery. 1991;117(5):519-528.
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1.
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References:
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Chemotherapeutic agents
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14.
15.
16.
17.
18.
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19.
SC
13.
M AN U
12.
TE D
11.
Hirai R, Takao K, Onoda K, Kokubun S, Ikeda M. Patients With Phantogeusia Show Increased Expression of T2R Taste Receptor Genes in Their Tongues. Ann Oto Rhinol Laryn. Feb 2012;121(2):113-118. Just T, Pau HW, Witt M, Hummel T. Contact endoscopic comparison of morphology of human fungiform papillae of healthy subjects and patients with transected chorda tympani nerve. Laryngoscope. Jul 2006;116(7):1216-1222. Hotta M, Endo S, Tomita H. Taste disturbance in two patients after dental anesthesia by inferior alveolar nerve block. Acta oto-laryngologica. Supplementum. 2002(546):94-98. Lee N, Duan H, Hebert MF, Liang CJ, Rice KM, Wang J. Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands. The Journal of biological chemistry. Sep 26 2014;289(39):2705527064. Tuccori M, Lapi F, Testi A, et al. Drug-induced taste and smell alterations: a case/non-case evaluation of an italian database of spontaneous adverse drug reaction reporting. Drug safety. Oct 1 2011;34(10):849-859. Raja JV, Rai P, Khan M, Banu A, Bhuthaiah S. Evaluation of gustatory function in HIV-infected subjects with and without HAART. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2013;42(3):216-221. Miles D, Baselga J, Amadori D, et al. Treatment of older patients with HER2positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA). Breast cancer research and treatment. Nov 2013;142(1):89-99. Pavlidis P, Gouveris C, Kekes G, Maurer J. Changes in electrogustometry thresholds, tongue tip vascularization, density and form of the fungiform papillae in smokers. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies. Aug 2014;271(8):2325-2331. Steinbach S, Hundt W, Vaitl A, et al. Taste in mild cognitive impairment and Alzheimer's disease. Journal of neurology. Feb 2010;257(2):238-246. Suto T, Meguro K, Nakatsuka M, et al. Disorders of "taste cognition" are associated with insular involvement in patients with Alzheimer's disease and vascular dementia: "Memory of food is impaired in dementia and responsible for poor diet". Int Psychogeriatr. Jul 2014;26(7):1127-1138. Haehner A, Boesveldt S, Berendse HW, et al. Prevalence of smell loss in Parkinson's disease--a multicenter study. Parkinsonism & related disorders. Aug 2009;15(7):490-494. Kashihara K, Hanaoka A, Imamura T. Frequency and characteristics of taste impairment in patients with Parkinson's disease: results of a clinical interview. Internal medicine. 2011;50(20):2311-2315. Pavlidis P, Gouveris H, Kekes G, Maurer J. Electrogustometry thresholds, tongue tip vascularization, and density and morphology of the fungiform papillae in diabetes. B-ENT. 2014;10(4):271-278.
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21.
22.
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McConnell RJ, Menendez CE, Smith FR, Henkin RI, Rivlin RS. Defects of taste and smell in patients with hypothyroidism. Am J Med. Sep 1975;59(3):354-364. Femiano F, Lanza A, Buonaiuto C, et al. Burning mouth syndrome and burning mouth in hypothyroidism: proposal for a diagnostic and therapeutic protocol. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. Jan 2008;105(1):e22-27. Woda A, Dao T, Gremeau-Richard C. Steroid dysregulation and stomatodynia (burning mouth syndrome). Journal of orofacial pain. Summer 2009;23(3):202210. Shiue I. Adult taste and smell disorders after heart, neurological, respiratory and liver problems: US NHANES, 2011-2012. International journal of cardiology. Jan 20 2015;179:46-48. Musialik J, Suchecka W, Klimacka-Nawrot E, Petelenz M, Hartman M, BlonskaFajfrowska B. Taste and appetite disorders of chronic hepatitis C patients. European journal of gastroenterology & hepatology. 2012;24(12):1400-1405. Manley KJ. Saliva composition and upper gastrointestinal symptoms in chronic kidney disease. Journal of renal care. Sep 2014;40(3):172-179. Hopcraft MS, Morgan MV, Satur JG, Wright FA. Utilizing dental hygienists to undertake dental examination and referral in residential aged care facilities. Community dentistry and oral epidemiology. Aug 2011;39(4):378-384. Brauchle F, Noack M, Reich E. Impact of periodontal disease and periodontal therapy on oral health-related quality of life. International dental journal. Dec 2013;63(6):306-311. Yoshinaka M, Yoshinaka MF, Ikebe K, Shimanuki Y, Nokubi T. Factors associated with taste dissatisfaction in the elderly. Journal of oral rehabilitation. Jul 2007;34(7):497-502. Hutton JL, Baracos VE, Wismer WV. Chemosensory dysfunction is a primary factor in the evolution of declining nutritional status and quality of life in patients with advanced cancer. J Pain Symptom Manag. Feb 2007;33(2):156-165. Almeida JP, Vartanian JG, Kowalski LP. Clinical predictors of quality of life in patients with initial differentiated thyroid cancers. Arch Otolaryngol Head Neck Surg. Apr 2009;135(4):342-346. Chen AM, Daly ME, Farwell DG, et al. Quality of Life Among Long-Term Survivors of Head and Neck Cancer Treated by Intensity-Modulated Radiotherapy. Jama Otolaryngol. Feb 2014;140(2):129-133. Miller SM, Naylor GJ. Unpleasant taste--a neglected symptom in depression. Journal of affective disorders. 1989;17(3):291-293. Amsterdam JD, Settle RG, Doty RL, Abelman E, Winokur A. Taste and Smell Perception in Depression. Biol Psychiat. Dec 1987;22(12):1481-1485. Lewandowski KE, DePaola J, Camsari GB, Cohen BM, Ongur D. Tactile, olfactory, and gustatory hallucinations in psychotic disorders: a descriptive study. Annals of the Academy of Medicine, Singapore. May 2009;38(5):383-385. Hausser-Hauw C, Bancaud J. Gustatory hallucinations in epileptic seizures. Electrophysiological, clinical and anatomical correlates. Brain : a journal of neurology. Apr 1987;110 ( Pt 2):339-359. Medicaid Coverage of Dental Benefits for Adults
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37.
38.
39.
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https://macpac.gov/wp-content/uploads/2015/06/Medicaid-Coverage-of-Dental-Benefitsfor-Adults.pdf Nagraj SK, Naresh S, Srinivas K, et al. Interventions for the management of taste disturbances. The Cochrane database of systematic reviews. 2014;11:CD010470.
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S0002-9343(16)30177-2
DOI:
10.1016/j.amjmed.2016.02.003
Reference:
AJM 13380
To appear in:
The American Journal of Medicine
Received Date: 27 November 2015 Revised Date:
26 January 2016
Accepted Date: 1 February 2016
Please cite this article as: Syed Q, Hendler KT, Koncilja K, The impact of aging and medical status on dysguesia, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.02.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title Page: Title: The impact of aging and medical status on dysguesia
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Authors: Quratulain Syed, M.D.
Emory University School of Medicine,
Tel: 404.778.1630 [email protected]
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49 Jesse Hill Jr. Drive, Atlanta, GA 30303
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Assistant Professor of Medicine,
Financial Disclosures and conflicts of interest: none
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Kevin T Hendler, DDS, FASGD
Diplomate, American Board of Special Care Dentistry Associate Professor, Emory University School of Medicine
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Director, Geriatric Dentistry, Ina T Allen Dental Center, Emory Healthcare 1841 Clifton Road, Atlanta, GA 30329
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404 728 6432
[email protected]
Financial Disclosures and conflicts of interest: none
Kenneth Koncilja, M.D. Cleveland Clinic,
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9500 Euclid Avenue X10, Cleveland, OH 44195 [email protected]
Corresponding author: Quratulain Syed, M.D. Assistant Professor of Medicine, Division of General Medicine and Geriatrics,
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Emory University School of Medicine,
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Financial Disclosures and conflicts of interest: none
49 Jesse Hill Jr. Drive, Atlanta, GA 30303 Tel: 404.778.1630 Fax: 404.778.1602
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[email protected]
Additional authors disclosure: All authors had access to the data and a role in writing
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the manuscript.
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Article type: clinical narrative review article
Key words: dysgeusia, weight loss, hospitalized elderly, long term care, oral care, polypharmacy
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Manuscript:
Clinical Significance/Key Points
residing in long term care facilities. •
Dysgeusia can impact a patient’s enjoyment of food, overall nutritional status and management of chronic diseases.
•
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Dysguesia is fairly prevalent in older adults, esp. those admitted in hospitals or
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•
Review of medications and attention to oral health should be prioritized in
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patients presenting with dysgeusia.
Abstract
Disorders of taste and/or smell can cause an aversion to food in a sick patient and
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therefore affect his/her ability to maintain optimal nutrition1. This can lead to a reduced level of strength, muscle mass, function, and quality of life. Additionally, reduced ability to differentiate between various intensities or concentrations of a tastant can result in
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increased intake of salt and sugar and exacerbation of chronic diseases such as heart failure and diabetes2.
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These implications can be heightened in the elderly who are particularly frail and are challenged by polypharmacy and multiple comorbid conditions. In this article, we will review the prevalence, etiology and management of taste disorders. Additionally, we will review the association between taste and smell disorders and how disorders of smell can affect perception of taste.
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Clinical Scenario Ms. Edwards is an eighty nine year old female nursing home resident admitted to an inpatient medicine service for failure to thrive, severe malnutrition, loss of appetite and a
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25 pound weight loss in the past six months. Past medical history is significant for
osteoporosis, congestive heart failure, chronic renal insufficiency and hypothyroidism. She has been hospitalized twice during the past 6 months for exacerbation of heart
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failure, with resultant adjustment of her heart failure medication regimen. She notes a
persistent loss of appetite and lack of taste in her food for the past six months, preventing
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her from enjoying her food. She denies any difficulty swallowing, nausea, vomiting, or abdominal pain on eating. She also denies being depressed. Basic blood work indicated acute renal insufficiency due to dehydration, which was corrected with intra venous fluids. Other blood work including electrolytes, liver function and thyroid function labs
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were unremarkable. She underwent an upper gastrointestinal endoscopy and a colonoscopy which failed to show any ulcers or evidence of malignancy.
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Terminology and Definitions
Taste disorders (dysgeusias) can be classified into qualitative and quantitative disorders.
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The qualitative disorders include parageusias (inadequate or wrong taste perception elicited by a stimulus) and phantogeusias (presence of a persistent, unpleasant taste in the absence of any stimulus). The quantitative disorders include ageusia (a complete loss of the ability to taste), hypogeusia (a partial loss of the ability to taste), and hypergeusia (enhanced gustatory sensitivity)3. Burning mouth syndrome (BMS) also referred to as
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glossodynia or somatodynia, is a sensation of spontaneous, continuous burning pain felt in the tongue or oral mucosa, commonly seen in post-menopausal women. Impairment in sense of smell is called dysosmia and complete loss of sense of smell is
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called anosmia.
Prevalence
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The National Health and Nutrition Examination Survey (NHANES) 2011-2012 reported that more than 5% of the over 142 million US respondents experienced taste disorders
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and more than 10% experienced smell disorder in the past 12 months. Gender was not associated with the prevalence of either disorder, but increasing age was associated with increasing prevalence of both taste and smell disorders 4. Additionally, taste disorders are more prevalent in hospitalized and institutionalized older adults compared to those living
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in the community5,6. Glazer et al reported taste disturbance in 13.9% of institutionalized individuals compared to 3.2% of community dwelling individuals7. Aging can affect gustatory function as observed by increasing of electrogustometry (EGM) thresholds and
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Anatomy
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reduction in density of fungiform papillae 8.
Gustatory receptor cells are present in the taste buds on the dorsal and lateral surfaces of the tongue, the soft palate, uvula, larynx, pharynx, epiglottis, and esophagus. These receptor cells are innervated by afferent neurons and are able to regenerate with a halflife of about 15 days. Transduction of the five taste stimuli, acid, salt, bitter, sweet, and umami (a pleasant savoury taste imparted by glutamate), occurs by different chemical
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transmission systems. Taste sensations are transported via 3 cranial nerves; Cranial Nerve VII innervates the anterior third of the tongue and the palate, Cranial Nerve IX innervates the back of the tongue, Cranial Nerve X innervates the oropharynx and the pharyngeal
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portion of the epiglottis. Additional taste receptors are found in the small intestine. The Trigeminal nerve (Cranial Nerve V) is also involved in the transfer of sensations such as the temperature, texture and spiciness of food. The brain stem, thalamus, and the anterior
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insula play a key role in the processing of the taste information by the central nervous system. Due to involvement of multiple nerve tracts, it's rather difficult to completely
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lose the sense of taste.
Olfaction on the other hand, relies only on the olfactory nerve, and its axons pass through the cribriform plate of the ethmoid bone prior to dissemination on the surface of the olfactory bulb. This makes it highly vulnerable to injury during head trauma. In this
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Etiology
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situation, a complete loss of sense of smell is more common.
Impairment in Sense of Olfaction and its effect on taste:
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Since the taste sensations are conducted by three major nerves, a complete loss of taste (ageusia) is very rare and only occurs in 3 % of all patients with dysgeusia3. Among those patients presenting for evaluation of loss of taste and smell, 70% report loss of smell alone or in addition to loss of taste. Less than 10% report an isolated loss of taste while only 4% have a solitary measurable loss in gustation3,9. Therefore, olfactory symptoms
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should be explored and olfactory function be evaluated in patients presenting with a complaint of loss of taste. Genetic:
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In a study involving patients with phantogeusia, there was increased expression rate of some of the T2R taste receptor genes compared to controls, hinting that increased
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expression of taste receptor genes may be involved in the pathogenesis of phantogeusia10.
Post-operative:
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Middle ear surgeries with resultant transection of the chorda tympani nerve can result in gustatory impairment11. Additionally, tonsillectomies, dental procedures such as extractions and treatment of abscessed teeth, and wearing dental prostheses can contribute to phantogeusia and glossodynia 3. There have been case reports of ageusia
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after the use of laryngeal mask airways for surgery, and compression of the lingual nerve has been hypothesized as the cause. Local anesthetic injected near the inferior alveolar nerve during dental procedures has been reported to cause ipsilateral loss of taste and
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few months12.
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atrophy of fungiform papillae. However, these symptoms have been noted to resolve in a
Medications:
Numerous medicines are excreted in saliva by carrier-mediated transport or passive diffusion13. They can affect sense of taste by various mechanisms including drug-receptor interaction, disturbance of action potential propagation in cell membranes of afferent and efferent neurons, and alteration of the neurotransmitter function. Additionally, limiting
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the access of taste chemicals to sensing receptors due to mucosal dryness, closing of taste pores, or altering the constituents of mucous or saliva can also impact the sense of taste14. A review of the Italian national database of spontaneous adverse drug reactions (ADR)
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(Agenzia Italiana del Farmaco) from 1988-2008 showed that taste alteration alone was reported in 75% of cases of ADRs and both taste and smell impairment were noted in
13% of ADRs. Macrolides, anti-mycotics, fluoroquinolones, protein kinase inhibitors,
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angiotensin converting enzyme (ACE) inhibitors, HMG-CoA reductase inhibitors
(statins), and proton pump inhibitors (PPI) were the leading culprits14. Resolution of
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symptoms varied, with improvement reported within days to a few months after discontinuation of the offending medicine.
Anti-retroviral medications have been associated with dysgeusia in HIV patients15. Chemotherapeutic drugs used for treatment of cancers, especially 5-fluorouracil and its
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oral analogs, have also been associated with dysgeusias, with greater prevalence in the elderly16. Numerous other commonly prescribed drugs, described in table II, can
Nicotine:
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contribute to dysgeusia.
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Smoking can affect taste acuity as smokers have increased EGM thresholds and decreased vascularization and density of fungiform papillae compared to non-smokers 17.
Dementia:
Patients with mild cognitive impairment (MCI) and Alzheimer’s dementia have increased impairment in olfaction and taste compared to controls18. Alzheimer’s dementia and
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vascular dementia can affect the insula and therefore taste cognition19. Additionally, medications prescribed for management of dementias (e.g., cholinesterase inhibitors) can also contribute to taste disturbance.
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Up to 70% of patients with Parkinson’s disease (PD) experience dysosmia 20 and 9% experience dysgeusia 21. Lewy body related degeneration has been observed in
pathological examination of the olfactory bulbs in patients with Parkinson’s Disease
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which can explain the strong association between dysosmia and Parkinson’s Disease . As taste information also connects to the amygdala and hippocampus, patients with
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Parkinson’s Disease can experience dysgeusia. Additionally, patients with Parkinson’s Disease may have underlying depression, poor oral hygiene, gastrointestinal disease, and zinc deficiency which may explain dysgeusia in absence of dysosmia.
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Endocrine disorders:
Diabetes can affect gustatory function. Diabetics have been observed to have higher electrogustometric (EGM) thresholds and lower density of the fungiform papillae
control.
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compared to age matched controls22. This can affect their food choices and glycemic
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Both dysgeusia and dysosmia have been reported in patients with untreated hypothyroidism, with improvement in symptoms after treatment of the thyroid disease 23. Burning mouth syndrome (BMS) has also been reported in a few case series as a presenting feature of hypothyroidism24. Due to increased prevalence of BMS in post-menopausal women, steroid dysregulation has also been hypothesized as a possible contributor25.
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Chronic Diseases: Upper respiratory disorders are frequently associated with both taste and smell disorders.
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Upto 38% of individuals with taste problems in NHANES 2011-2012 reported
experiencing nasal congestion 4. Additionally, survey participants with a history of heart failure, heart attack, liver problems and impaired vision reported increased taste
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disturbance in the past 12 months compared to participants who didn’t have these
medical conditions. This association was valid even after adjustment for risk factors
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including head or nasal injury or sinus infections26.
Dysgeusia including metallic taste and impairment in identification and intensity of different flavors has also been observed in iIndividuals with chronic kidney disease and chronic hepatitis C. Individuals with chronic hepatitis C experience problems in
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identification and intensity of different food flavors. Numerous hypotheses have been put forth including alteration in function of affected brain cells in the taste area by the virus, and alteration in secretion of neurotransmitters involved in taste perception 27.
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Uremic state in chronic kidney disease can affect salivary flow leading to dry mouth and dysgeusia28. Additionally, medications and zinc deficiency can affect taste perception in
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patients with chronic kidney disease. The association between heart diseases and taste disturbance is usually due to concomitant renal dysfunction and adverse effects of medications.
Electrolyte and Nutritional Deficiency:
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The principle nutrient deficiency commonly associated with taste loss is zinc. A reduction in number and size of taste buds in zinc deficient animal models has been demonstrated. However, this has not been consistently verified in double-blind trials.
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Vitamin A deficiency has been associated with atrophy of taste buds in animal models and vitamin B12 deficiency can lead to atrophic glossitis resulting in loss of taste
sensation. Additionally, electrolyte disturbances including hyponatremia have been
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Oral/Dental conditions:
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reported to cause taste disturbance.
The mouth is the gateway for food into the body. Therefore, changes in the oral cavity can have an impact on taste. Older adults frequently have poor oral hygiene with increased dental caries and periodontal disease. Poor oral health may be more
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pronounced in institutionalized older adults where access to dental care may be limited and daily oral hygiene inadequate 29. Additionally, xerostomia (dry mouth) is frequently experienced by patients taking numerous medications and patients with dehydration,
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diabetes, Sjogren’s Disease and thyroid conditions. Dental caries, periodontal disease, candidiasis, stomatitis, dental-alveolar infections,
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xerostomia, tumors and mechanical trauma can lead to taste disorders in the elderly7,30. Dentures, especially those that do not fit well, can cause traumatic ulcers, stomatitis and fungal infections. Additionally, patients wearing dentures which cover the hard palate report increased taste problems31.
Malignancies:
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Chemosensory dysfunction is fairly prevalent in individuals with advanced malignancies. One study showed that 86% of individuals with advanced cancer (defined as locally
persistent bad taste in the mouth and taste distortion 32.
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recurrent or metastatic) reported some degree of chemosensory abnormality, especially
Radioactive iodine therapy (RIT) for thyroid cancers has been shown to affect salivary
increased oral pain, problems with taste and chewing33.
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flow especially from parotid glands, and high dose RIT has been associated with
Head and neck cancer patients treated with radiotherapy and/or chemotherapeutic agents
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can develop altered taste acuity, radiation induced xerostomia and dysphagia which can lead to anorexia. However, with the use of intensity-modulated radiotherapy (IMRT) in the treatment of head and neck cancer, > 80% cancer survivors reported normal or near-
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normal taste function at 3 and 5 years after IMRT34.
Mental health disorders and Epilepsy:
Dysgeusia has been reported in depressed, non-delusional patients35. Impairment in
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supra-threshold measures of sucrose taste intensities has been shown in patients with major depression compared to controls36. Gustatory (and olfactory) hallucinations can
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also be a feature of psychiatric disorders such as schizophrenia, schizoaffective disorder and bipolar disorder, or a manifestation of parietal, temporal or temporo-parietal partial seizures 37,38.
Evaluation and management of taste disorders
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It is important to screen for taste or smell disorders if your patient is experiencing appetite problems and weight loss. A proposed screening question below has been adapted from NHANES 2011-2012 survey:
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Have you experienced problems with taste or smell in the past 12 months?
A detailed history should include questions about salivary flow, problems with taste and
hygiene and ear or upper respiratory infections.
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smell, chewing problems, pain in the oral cavity, problems with teeth and dentures, dental
A loss of taste can be both regional and quality specific with different thresholds for
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different substances in different regions of the tongue, palate, and pharynx. Primary care physicians can use easily available stimuli such as sugar (sweet), citric acid (acid), sodium chloride (salty), or caffeine or quinine (bitter) to do a quick and objective taste assessment in their office. A referral to an otolaryngologist may be warranted for detailed
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evaluation.
Evaluation and management of upper respiratory infections, oral candidiasis, and basic blood work to rule out metabolic or endocrine disorders should be pursued.
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A thorough review of medications can help identify medications contributing to dysgeusia. Based on the co-morbidities and indication of the culprit medication, an
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evaluation to stop the medicine or change to an alternative medication with less taste distortion side-effects may be warranted. Taste related side effects should be discussed as part of the potential risks of prescribed medications prior to initiation of therapy. Many older adults lack private dental insurance and Medicare does not cover routine dental care. Medicaid dental coverage for adults varies by state with only about one half of the states paying for preventive dental care or restorative services39. This greatly limits
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access to dental care for low income older adults who rely on Medicaid. A dental referral for examination and treatment of oral disease should be a priority when there is a complaint of altered taste. This should also include evaluation and management of dry
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mouth. Additionally, primary care physicians should discuss the importance of good oral hygiene and the role of good oral health in the overall health of an individual.
Currently there is insufficient evidence to recommend zinc supplementation to improve
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Follow up on Ms. Edwards
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taste perception or acuity in zinc deficiency related or idiopathic dysgeusia 40.
Ms. Edwards continued to eat poorly and complain of taste impairment during her hospital stay. The inpatient medical team reviewed her medications with the help of a
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clinical pharmacist and identified numerous medicines including Lisinopril, atorvastatin, digoxin, levothyroxine, donepezil and oxybutynin which may cause taste problems. Based on clinical indication and weighing benefits and risks of treatments, the team
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decided to stop donepezil and oxybutynin. She was advised to see a dentist and her primary care physician on discharge from hospital. Her dentist diagnosed periodontal
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disease which was treated. She saw a dietician who educated her and her family on optimal nutrition and a liberalized diet. Her primary care doctor and cardiologist agreed to discontinue digoxin. Six months later, her appetite gradually improved and her weight stabilized.
This case highlights the importance of a multi-disciplinary approach to the management of taste disorders in older adults and how medical status, including oral health and
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medications, can impact taste disorders. Recognizing the causes of dysgeusia and knowing how to treat this can have a great impact on general health and overall well-
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being of patients.
Smell disturbance on history
Taste disturbance or mixed taste and smell disturbance on history
Examine oral cavity and dentition
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Review medications
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Patient complains of taste disturbance
Refer to dentist if needed
Screen for signs/symptoms of endocrine or metabolic disorders
Treat URI
Check appropriate lab work-TSH, HbA1c, LFTs
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Change offending medicines if possible
Screen for upper respiratory infections (URI)
Figure 1: schematic diagram of management of taste disorders
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Chronic medical conditions contributing to Dysgeusia Sinusitis/upper respiratory infections
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Chronic hepatitis C Chronic Kidney Disease
Heart Diseases
Cognitive disorders/dementias Parkinson’s Disease Malignancies
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Thyroid disorders, esp. hypothyroidism
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Diabetes Mellitus
candidiasis
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Dental/oral: periodontal disease, dental caries, oropharyngeal
Mental health disorders and epilepsy
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Table 1: Chronic medical conditions contributing to Dysgeusia
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Common medicines in the groups
with dysgeusia
associated with dysgeusia
Anti-microbial medicines
Macrolides, fluoroquinolones, ampicillin,
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Medication groups frequently associated
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metronidazole, tetracycline, trimethoprimsulfamethoxazole, amphotericin B,
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terbinafine and other anti-mycotic drugs
Angiotensin converting enzyme (ACE) inhibitors Anti-arrhythmic medications
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HMG-CoA reductase inhibitors (statins)
Captopril, Ramipril
Amiodarone, Procainamide Atorvastatin, Simvastatin
Proton Pump Inhibitors (PPI)
Atazanavir, Darunavir, and Ritonavir
Anti-epileptic medications
Carbamazepine, Phenytoin, Topiramate
Diuretics
Acetazolamide
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Anti-retroviral medications
Levo-dopa
Protein kinase inhibitors
Sunitinib, Erlotinib, Imatinib
Anti-cholinergic medicines
Anti-spasmodics, anti-muscarinics,
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Dopamine precursor
tricyclic anti-depressants Psychiatric medicines
Lithium, Aripiprazole
Gout medicines
Colchicine, Allopurinol
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Muscle relaxants
Baclofen
Endocrine medications
Anti-thyroid medications, Corticosteroids, Levothyroxine 5-fluorouracil, Cisplatin
Table II: Medications contributing to Dysgeusia
4. 5.
6. 7.
8.
9.
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Vanderwee K, Clays E, Bocquaert I, Gobert M, Folens B, Defloor T. Malnutrition and associated factors in elderly hospital patients: a Belgian cross-sectional, multi-centre study. Clinical nutrition. Aug 2010;29(4):469-476. Bennett SJ, Lane KA, Welch J, Perkins SM, Brater DC, Murray MD. Medication and dietary compliance beliefs in heart failure. West J Nurs Res. Dec 2005;27(8):977-993; discussion 994-979. Fark T, Hummel C, Hahner A, Nin T, Hummel T. Characteristics of taste disorders. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2013;270(6):1855-1860. Bhattacharyya N, Kepnes LJ. Contemporary assessment of the prevalence of smell and taste problems in adults. Laryngoscope. May 2015;125(5):1102-1106. Solemdal K, Sandvik L, Willumsen T, Mowe M. Taste ability in hospitalised older people compared with healthy, age-matched controls. Gerodontology. Mar 2014;31(1):42-48. Toffanello ED, Inelmen EM, Imoscopi A, et al. Taste loss in hospitalized multimorbid elderly subjects. Clin Interv Aging. 2013;8:167-174. Glazar I, Urek MM, Brumini G, Pezelj-Ribaric S. Oral sensorial complaints, salivary flow rate and mucosal lesions in the institutionalized elderly. Journal of oral rehabilitation. Feb 2010;37(2):93-99. Pavlidis P, Gouveris H, Anogeianaki A, Koutsonikolas D, Anogianakis G, Kekes G. Age-related changes in electrogustometry thresholds, tongue tip vascularization, density, and form of the fungiform papillae in humans. Chemical senses. Jan 2013;38(1):35-43. Deems DA, Doty RL, Settle RG, et al. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Archives of Otolaryngology--Head & Neck Surgery. 1991;117(5):519-528.
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References:
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Chemotherapeutic agents
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15.
16.
17.
18.
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13.
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12.
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Hirai R, Takao K, Onoda K, Kokubun S, Ikeda M. Patients With Phantogeusia Show Increased Expression of T2R Taste Receptor Genes in Their Tongues. Ann Oto Rhinol Laryn. Feb 2012;121(2):113-118. Just T, Pau HW, Witt M, Hummel T. Contact endoscopic comparison of morphology of human fungiform papillae of healthy subjects and patients with transected chorda tympani nerve. Laryngoscope. Jul 2006;116(7):1216-1222. Hotta M, Endo S, Tomita H. Taste disturbance in two patients after dental anesthesia by inferior alveolar nerve block. Acta oto-laryngologica. Supplementum. 2002(546):94-98. Lee N, Duan H, Hebert MF, Liang CJ, Rice KM, Wang J. Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands. The Journal of biological chemistry. Sep 26 2014;289(39):2705527064. Tuccori M, Lapi F, Testi A, et al. Drug-induced taste and smell alterations: a case/non-case evaluation of an italian database of spontaneous adverse drug reaction reporting. Drug safety. Oct 1 2011;34(10):849-859. Raja JV, Rai P, Khan M, Banu A, Bhuthaiah S. Evaluation of gustatory function in HIV-infected subjects with and without HAART. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2013;42(3):216-221. Miles D, Baselga J, Amadori D, et al. Treatment of older patients with HER2positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA). Breast cancer research and treatment. Nov 2013;142(1):89-99. Pavlidis P, Gouveris C, Kekes G, Maurer J. Changes in electrogustometry thresholds, tongue tip vascularization, density and form of the fungiform papillae in smokers. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies. Aug 2014;271(8):2325-2331. Steinbach S, Hundt W, Vaitl A, et al. Taste in mild cognitive impairment and Alzheimer's disease. Journal of neurology. Feb 2010;257(2):238-246. Suto T, Meguro K, Nakatsuka M, et al. Disorders of "taste cognition" are associated with insular involvement in patients with Alzheimer's disease and vascular dementia: "Memory of food is impaired in dementia and responsible for poor diet". Int Psychogeriatr. Jul 2014;26(7):1127-1138. Haehner A, Boesveldt S, Berendse HW, et al. Prevalence of smell loss in Parkinson's disease--a multicenter study. Parkinsonism & related disorders. Aug 2009;15(7):490-494. Kashihara K, Hanaoka A, Imamura T. Frequency and characteristics of taste impairment in patients with Parkinson's disease: results of a clinical interview. Internal medicine. 2011;50(20):2311-2315. Pavlidis P, Gouveris H, Kekes G, Maurer J. Electrogustometry thresholds, tongue tip vascularization, and density and morphology of the fungiform papillae in diabetes. B-ENT. 2014;10(4):271-278.
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McConnell RJ, Menendez CE, Smith FR, Henkin RI, Rivlin RS. Defects of taste and smell in patients with hypothyroidism. Am J Med. Sep 1975;59(3):354-364. Femiano F, Lanza A, Buonaiuto C, et al. Burning mouth syndrome and burning mouth in hypothyroidism: proposal for a diagnostic and therapeutic protocol. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. Jan 2008;105(1):e22-27. Woda A, Dao T, Gremeau-Richard C. Steroid dysregulation and stomatodynia (burning mouth syndrome). Journal of orofacial pain. Summer 2009;23(3):202210. Shiue I. Adult taste and smell disorders after heart, neurological, respiratory and liver problems: US NHANES, 2011-2012. International journal of cardiology. Jan 20 2015;179:46-48. Musialik J, Suchecka W, Klimacka-Nawrot E, Petelenz M, Hartman M, BlonskaFajfrowska B. Taste and appetite disorders of chronic hepatitis C patients. European journal of gastroenterology & hepatology. 2012;24(12):1400-1405. Manley KJ. Saliva composition and upper gastrointestinal symptoms in chronic kidney disease. Journal of renal care. Sep 2014;40(3):172-179. Hopcraft MS, Morgan MV, Satur JG, Wright FA. Utilizing dental hygienists to undertake dental examination and referral in residential aged care facilities. Community dentistry and oral epidemiology. Aug 2011;39(4):378-384. Brauchle F, Noack M, Reich E. Impact of periodontal disease and periodontal therapy on oral health-related quality of life. International dental journal. Dec 2013;63(6):306-311. Yoshinaka M, Yoshinaka MF, Ikebe K, Shimanuki Y, Nokubi T. Factors associated with taste dissatisfaction in the elderly. Journal of oral rehabilitation. Jul 2007;34(7):497-502. Hutton JL, Baracos VE, Wismer WV. Chemosensory dysfunction is a primary factor in the evolution of declining nutritional status and quality of life in patients with advanced cancer. J Pain Symptom Manag. Feb 2007;33(2):156-165. Almeida JP, Vartanian JG, Kowalski LP. Clinical predictors of quality of life in patients with initial differentiated thyroid cancers. Arch Otolaryngol Head Neck Surg. Apr 2009;135(4):342-346. Chen AM, Daly ME, Farwell DG, et al. Quality of Life Among Long-Term Survivors of Head and Neck Cancer Treated by Intensity-Modulated Radiotherapy. Jama Otolaryngol. Feb 2014;140(2):129-133. Miller SM, Naylor GJ. Unpleasant taste--a neglected symptom in depression. Journal of affective disorders. 1989;17(3):291-293. Amsterdam JD, Settle RG, Doty RL, Abelman E, Winokur A. Taste and Smell Perception in Depression. Biol Psychiat. Dec 1987;22(12):1481-1485. Lewandowski KE, DePaola J, Camsari GB, Cohen BM, Ongur D. Tactile, olfactory, and gustatory hallucinations in psychotic disorders: a descriptive study. Annals of the Academy of Medicine, Singapore. May 2009;38(5):383-385. Hausser-Hauw C, Bancaud J. Gustatory hallucinations in epileptic seizures. Electrophysiological, clinical and anatomical correlates. Brain : a journal of neurology. Apr 1987;110 ( Pt 2):339-359. Medicaid Coverage of Dental Benefits for Adults
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