Dysgeusia, also known as parageusia, is a distortion of the sense of taste. Dysgeusia is also often associated with ageusia, which is the complete lack of taste, and hypogeusia, which is a decrease in taste sensitivity.Steven K. Feske and Martin A. Samuels, Office Practice of Neurology 2nd ed. (Philadelphia: Elsevier Science, 2003) 114. An alteration in taste or smell may be a secondary process in various disease states, or it may be the primary symptom. The distortion in the sense of taste is the only symptom, and diagnosis is usually complicated since the sense of taste is tied together with other sensory systems. Common causes of dysgeusia include chemotherapy, asthma treatment with albuterol, and zinc deficiency. Liver disease, hypothyroidism, and rarely, certain types of seizures can also lead to dysgeusia. Different drugs can also be responsible for altering taste and resulting in dysgeusia. Due to the variety of causes of dysgeusia, there are many possible treatments that are effective in alleviating or terminating the symptoms. These include artificial saliva, pilocarpine, zinc supplementation, alterations in drug therapy, and alpha lipoic acid.

Signs and symptoms The alterations in the sense of taste, usually a metallic taste, and sometimes smell are the only symptoms.

Causes

Chemotherapy A major cause of dysgeusia is chemotherapy for cancer. Chemotherapy often induces damage to the oral cavity, resulting in oral mucositis, oral infection, and salivary gland dysfunction. Oral mucositis consists of inflammation of the mouth, along with sores and ulcers in the tissues. Healthy individuals normally have a diverse range of microbial organisms residing in their oral cavities; however, chemotherapy can permit these typically non-pathogenic agents to cause serious infection, which may result in a decrease in saliva. In addition, patients who undergo radiation therapy also lose salivary tissues. Saliva is an important component of the taste mechanism. Saliva both interacts with and protects the taste receptors in the mouth. Saliva mediates sour and sweet tastes through bicarbonate ions and glutamate, respectively. The salt taste is induced when sodium chloride levels surpass the concentration in the saliva. It has been reported that 50% of chemotherapy patients have had either dysgeusia or another form of taste impairment. Examples of chemotherapy treatments that can lead to dysgeusia are cyclophosphamide, cisplatin, vismodegib, and etoposide. The exact mechanism of chemotherapy-induced dysgeusia is unknown.

Taste buds

Distortions in the taste buds may give rise to dysgeusia. In a study conducted by Masahide Yasuda and Hitoshi Tomita from Nihon University of Japan, it has been observed that patients with this taste disorder have fewer microvilli than normal. In addition, the nucleus and cytoplasm of the taste bud cells have been reduced. Based on their findings, dysgeusia results from loss of microvilli and the reduction of Type III intracellular vesicles, all of which could potentially interfere with the gustatory pathway. Radiation to head and neck also results in direct destruction of taste buds, apart from effects of altered salivary output.

Zinc deficiency

Another primary cause of dysgeusia is zinc deficiency. While the exact role of zinc in dysgeusia is unknown, it has been cited that zinc is partly responsible for the repair and production of taste buds. Zinc somehow directly or indirectly interacts with carbonic anhydrase VI, influencing the concentration of gustin, which is linked to the production of taste buds. It has also been reported that patients treated with zinc experience an elevation in calcium concentration in the saliva. In order to work properly, taste buds rely on calcium receptors.Joseph M. Bicknell, MD and Robert V. Wiggins, MD, "Taste Disorder From Zinc Deficiency After Tonsillectomy," The Western Journal of Medicine Oct.1988: 458. Zinc "is an important cofactor for alkaline phosphatase, the most abundant enzyme in taste bud membranes; it is also a component of a parotid salivary protein important to the development and maintenance of normal taste buds".

Taste modifiers Miraculin, found in Synsepalum dulcificum (miracle berries), binds to the taste buds and causes normally sour foods to taste sweet.

Gymnema sylvestre contains gymnemic acids, which temporarily suppress the taste of sweetness.

Drugs

There are also a wide variety of drugs that can trigger dysgeusia, including zopiclone, H1-antihistamines, such as azelastine and emedastine. Approximately 250 drugs affect taste, including Paxlovid, a drug used to treat COVID-19.Steven K. Feske and Martin A. Samuels, Office Practice of Neurology 2nd ed. (Philadelphia: Elsevier Science, 2003) 119. Some describe so-called "Paxlovid mouth" as like a "mouthful of dirty pennies and rotten soymilk", according to the Wall Street Journal.

The sodium channels linked to taste receptors can be inhibited by amiloride, and the creation of new taste buds and saliva can be impeded by antiproliferative drugs. Saliva can have traces of the drug, giving rise to a metallic flavor in the mouth; examples include lithium carbonate and tetracyclines. Drugs containing sulfhydryl groups, including penicillamine and captopril, may react with zinc and cause deficiency. Metronidazole and chlorhexidine have been found to interact with metal ions that associate with the cell membrane. Drugs that act by blocking the renin–angiotensin–aldosterone system, for example by antagonizing the angiotensin II receptor (as eprosartan does), have been linked to dysgeusia. There are a few case reports claiming calcium channel blockers like amlodipine also cause dysgeusia by blocking calcium sensitive taste buds.

Pregnancy

Changes in hormone levels during pregnancy, such as estrogen, can affect the sense of taste. A study found that 93 percent of pregnant women reported some change in taste during pregnancy.

Miscellaneous causes Xerostomia, also known as dry mouth syndrome, can precipitate dysgeusia because normal salivary flow and concentration are necessary for taste. Injury to the glossopharyngeal nerve can result in dysgeusia. In addition, damage done to the pons, thalamus, and midbrain, all of which compose the gustatory pathway, can be potential factors.R. K. Mal and M. A. Birchall, "Dysgeusia related to urinary obstruction from benign prostatic disease: a case control and qualitative study," European Archives of Oto-Rhino Laryngology 24 Aug. 2005:178. In a case study, 22% of patients who were experiencing a bladder obstruction were also experiencing dysgeusia. Dysgeusia was eliminated in 100% of these patients once the obstruction was removed. Although it is uncertain what the relationship between bladder relief and dysgeusia entails, it has been observed that the areas responsible for urinary system and taste in the pons and cerebral cortex in the brain are close in proximity.

Dysgeusia can be a symptom of head and neck cancer. In this case it often present together with having dry mouth.

Dysgeusia often occurs for unknown reasons. A wide range of miscellaneous factors may contribute to this taste disorder, such as gastric reflux, lead poisoning, and diabetes mellitus.Norman M. Mann, MD, "Management of Smell and Taste Problems," Cleveland Clinic Journal of Medicine Apr. 2002: 334. A minority of pine nuts can apparently cause taste disturbances, for reasons which are not entirely proven.

Certain pesticides can have damaging effects on the taste buds and nerves in the mouth. These pesticides include organochloride compounds and carbamate pesticides.

Damage to the peripheral nerves, along with injury to the chorda tympani branch of the facial nerve, also cause dysgeusia. A surgical risk for laryngoscopy and tonsillectomy include dysgeusia. Patients with burning mouth syndrome, primarily menopausal women, often have dysgeusia as well.Giuseppe Lauria, Alessandra Majorana, Monica borgna, Raffaella Lombardi, Paola Penza, Alessandro padovani, and Pierluigi Sapelli, "Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome," Pain 11 Mar. 2005: 332, 336.

Normal function

The sense of taste is based on the detection of chemicals by specialized taste cells in the mouth. The mouth, throat, larynx, and esophagus all have taste buds, which are replaced every ten days. Each taste bud contains receptor cells. Afferent nerves make contact with the receptor cells at the base of the taste bud. A single taste bud is innervated by several afferent nerves, while a single efferent fiber innervates several taste buds. Fungiform papillae are present on the anterior portion of the tongue while circumvallate papillae and foliate papillae are found on the posterior portion of the tongue. The salivary glands are responsible for keeping the taste buds moist with saliva.

A single taste bud is composed of four types of cells, and each taste bud has between 30 and 80 cells. Type I cells are thinly shaped, usually in the periphery of other cells. They also contain high amounts of chromatin. Type II cells have prominent nuclei and nucleoli with much less chromatin than Type I cells. Type III cells have multiple mitochondria and large vesicles. Type I, II, and III cells also contain synapses. Type IV cells are normally rooted at the posterior end of the taste bud. Every cell in the taste bud forms microvilli at the ends.

Diagnosis In general, gustatory disorders are challenging to diagnose and evaluate. Because gustatory functions are tied to the sense of smell, the somatosensory system, and the perception of pain (such as in tasting spicy foods), it is difficult to examine sensations mediated through an individual system. In addition, gustatory dysfunction is rare when compared to olfactory disorders.Hummel T, Knecht M. Smell and taste disorders. In: Calhoun KH, ed. Expert Guide to Otolaryngology. Philadelphia, Pa: American College of Physicians; 2001:650-664.

Diagnosis of dysgeusia begins with the patient being questioned about salivation, swallowing, chewing, oral pain, previous ear infections (possibly indicated by hearing or balance problems), oral hygiene, and stomach problems. The initial history assessment also considers the possibility of accompanying diseases such as diabetes mellitus, hypothyroidism, or cancer. A clinical examination is conducted and includes an inspection of the tongue and the oral cavity. Furthermore, the ear canal is inspected, as lesions of the chorda tympani have a predilection for this site.

Gustatory testing

In order to further classify the extent of dysgeusia and clinically measure the sense of taste, gustatory testing may be performed. Gustatory testing is performed either as a whole-mouth procedure or as a regional test. In both techniques, natural or electrical stimuli can be used. In regional testing, 20 to 50 μL of liquid stimulus is presented to the anterior and posterior tongue using a pipette, soaked filter-paper disks, or cotton swabs. In whole mouth testing, small quantities (2-10 mL) of solution are administered, and the patient is asked to swish the solution around in the mouth.

Threshold tests for sucrose (sweet), citric acid (sour), sodium chloride (salty), and quinine or caffeine (bitter) are frequently performed with natural stimuli. One of the most frequently used techniques is the "three-drop test". In this test, three drops of liquid are presented to the subject. One of the drops is of the taste stimulus, and the other two drops are pure water. Threshold is defined as the concentration at which the patient identifies the taste correctly three times in a row.