sign in sign up
<<
Home , Ageusia, Head, Hypogeusia, Hyposmia, Olfactory system, Parosmia

REVIEW

NORMAN M. MANN, MD Assistant Professor of , Director, Smell and Clinic, University of Connecticut Health Center, Farmington

Management of smell and taste problems

■ ABSTRACT HE LOSS OF SMELL or taste too often does T not get the medical attention it deserves. Lost or impaired smell or taste should be taken seriously, as This is unfortunate because of the serious it puts a person at higher risk for toxic exposures, such as implications for the patient’s well-being. gas leaks, smoke, and rotting , and it also takes away In many patients, smell or taste problems the enjoyment of some of life’s , such as the follow a viral upper respiratory tract , fragrance of flowers or the taste of good food or fine . which can damage sensory cells. These In many patients, the loss follows a viral upper respiratory patients need to be told that the damaged cells tract infection, and the only real treatment is to reassure may regenerate with time, resulting in the patients that the problem may resolve if the damaged return of smell and taste sensation. In other sensory cells regenerate. In other patients, the loss has patients, the loss has more subtle causes and requires a more in-depth workup. This article more subtle causes and deserves a careful investigation presents an approach to all patients with and appropriate treatment. This article reviews the proper impaired smell or taste. steps to take when investigating and treating chemosensory difficulties. ■ THE RISKS

■ KEY POINTS Loss or impairment of smell or taste puts people at greater risk of toxic exposures. With the loss Aside from increasing the risk of toxic exposures, the loss of of smell, they may be unable to detect leaking smell and taste often to , anorexia, and gas, smoke, or the of rotting food. weight loss. Interestingly, 80% of the patients seen in our smell and taste clinic have not been told by A thorough workup includes smell and taste testing, their physician to get a gas detector in the imaging studies, and testing. home. With the loss of smell and taste, many Gastric reflux is a common cause of taste dysfunction. pleasurable life experiences disappear, such as the fragrance of or flowers or the taste of good food or fine wine, and this puts the individual at higher risk for depression, anorexia, and weight loss. According to one estimate,1,2 more than 2 million adult Americans have some type of chemosensory disorder.

■ CAUSES OF SMELL DYSFUNCTION

Organs of smell sensation The of smell involves the passage of odor-stimulant through the nasal

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 4 APRIL 2002 329 SMELL AND TASTE PROBLEMS MANN

canal, where they interact with olfactory cells University of Pennsylvania, it has been report- in the nasal . Messages are then ed as the cause in 17.6% of cases.4 It has been sent via the olfactory (first cranial) nerves stated that 5% to 30% of patients with through the of the ethmoid injury have some olfactory loss.5 This may be bone to the in the , locat- due to blockage of the nasal canal, but the ed just above the . Thereafter, informa- most common cause is injury to the delicate tion is transmitted to different portions of the olfactory nerves as they travel from the nasal brain. Olfactory cells are thought to regener- canal through the cribriform plate to the ate every 30 or 60 days.3 olfactory bulb. Even mild jarring injuries can cause disruption of the neural pathways. Types of smell impairment Damage to the bulb itself and other central Normosmia is the name given to normal areas can also occur. smell. Smell dysfunction can have various pre- sentations: Nasal polyps, tumors • , diminished Nasal polyps and tumors in the nasal canal • , aberrant odor , either can impede the progress of odorants. Polyps without an odor () or are common. The incidence of polyps as a with an odor stimulus (distortion) cause of smell impairment varies in reports • , total loss of smell. from 41% to 69%.6 People who have lost their sense of smell sometimes retain their ability to detect pun- Endocrine conditions gent such as ammonia; however, this is Endocrine disturbances such as mel- due to stimulation of the trigeminal (fifth cra- litus,7 , and hypogonadism nial) nerve endings, which cover the oral cav- (eg, Turner syndrome, Kallmann syndrome)8 ity as well as the nose. are occasionally associated with olfactory Loss of smell can be the result of either impairment. Kallmann syndrome is charac- mechanical obstruction of or neurologic dam- terized by hypogonadotropic hypogonadism 25% of patients age to the , the neuroepithelium in with agenesis of the olfactory bulbs. Adrenal with smell loss the nasal canal, or the central olfactory ele- insufficiency9 and pseudohypoparathyroid- ments. In some patients, odorants are blocked ism10 may also present with olfactory dys- had a recent from reaching olfactory receptors, while in function. viral respiratory others peripheral olfactory receptors, nerve conduction pathways, or central olfactory Aging infection areas are damaged. A loss of olfactory sensitivity occurs with age. Degenerative changes occur in receptors in the nasal canal and even the olfactory bulb. At our clinic, mechanical obstruction is most The pathways can also be commonly due to rhinosinusitis (25% of affected. According to some estimates, almost cases). Allergic and nonallergic rhinitis are everyone has some type of smell impairment significant causes of obstruction. by age 60 or 70, and half of those in their 80s are anosmic.11 Viral infection From 14% to 25% of patients who report par- Environmental toxins tial or total impairment of smell have had a Environmental toxins can cause severe distur- recent viral upper respiratory tract infection. bance in the . They can enter Viral infection is thought to damage peripher- through the blood stream or inspired air. al olfactory receptors and neural pathways to Injury can involve the neuroepithelium or the the brain. olfactory nerves or both, and it can be reversible or irreversible. For example, expo- Head trauma sure to arsenic, benzene, carbon disulfide,12 At our clinic, head trauma has been the cause cadmium, sulfur dioxide, , chromium of olfactory impairment in 11% of cases; at the fumes, and cigarette smoke13 can produce

330 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 4 APRIL 2002 T ABLE 1 Drugs that can cause impaired smell or taste and Amitriptyline, carbamazepine, clomipramine, clozapine, desipramine, doxepin, fluoxetine, imipramine, , phenytoin, trifluoperazine Antihistamines and cold medications Chlorpheniramine, loratadine, pseudoephedrine, terfenadine Antihypertensives and cardiac medications Acetazolamide, adenosine, , benazepril and hydrochlorothiazide, betaxolol, captopril, clonidine, diltiazem, enalapril, ethacrynic , nifedipine, propranolol, spironolactone Anti-inflammatories Auranofin, colchicine, dexamethasone, diclofenac, , gold, hydrocortisone, d-penicil- lamine, penicillamine Antimicrobials Ampicillin, ciprofloxacin, clarithromycin, ofloxacin, streptomycin, tetracyclines Antineoplastics Cisplatin, doxorubicin, methotrexate, vincristine Bronchodilators and other medications Albuterol, cromolyn , flunisolide, metaproterenol, terbutaline Lipid-lowering drugs Cholestyramine, clofibrate, fluvastatin, gemfibrozil, lovastatin, pravastatin Muscle relaxants and drugs for parkinsonism Baclofen, dantrolene, levodopa Radiation of the head Suggest Vasodilators a home gas Dipyridamole, nitroglycerin patch detector for REPRINTED WITH PERMISSION FROM SCHIFFMAN SS. TASTE AND SMELL LOSSES IN NORMAL AGING AND DISEASE. JAMA 1997; 278:1357–1362. patients with impaired smell smell abnormalities. are also impor- can have compli- tant offenders. cations such as the inability to identify odors.

Drugs Psychiatric conditions Drugs in many major therapeutic categories Psychiatric conditions such as depression and have been known to cause smell impairment may also be associated with (TABLE 1). impairment of smell.

Neurologic diseases Congenital defects Parkinsonism is frequently associated Some patients complain of the inability to with olfactory dysfunction (dopaminergic smell since birth. In most cases, this is con- medication has no effect on olfaction). genital anosmia,15 a condition in which the Alzheimer disease can present initially with primary either are absent or the problem of anosmia, possibly due to are hypoplastic and lack cilia. However, some- deposits of neuritic plaques in times the loss may have followed a forgotten pathways.14 Huntington chorea and the or viral infection. Magnetic reso- demyelination of can also be nance imaging (MRI) of the brain can con- associated with impairment of smell. firm the absence of the olfactory bulb.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 4 APRIL 2002 331 SMELL AND TASTE PROBLEMS MANN

Autoimmune disorders stage, the patient is given two bottles—a Sjögren syndrome (with accompanying symp- “live” bottle (containing butanol dilution) toms of , nasal, and dryness) is often and a “blank” bottle (containing plain accompanied by impaired smell due to lym- )—and is asked to choose the bottle with phocytic infiltration into the nasal canal and the butanol. the lacrimal and salivary glands. It shares cer- The test starts with the weakest concen- tain autoimmune characteristics with rheuma- tration and proceeds to progressively stronger toid arthritis, scleroderma, and systemic lupus concentrations until the patient can detect erythematosus. Involvement of the central the smell. The test continues until the patient and spinal cord has been either gives five consecutive correct answers reported.16,17 or consistently shows no ability to detect the butanol. A numerical score is then given. ■ OFFICE TESTING FOR IMPAIRED SMELL This part of the test usually takes about 20 minutes. Several simple chemosensory tests can be Next, the odor identification component done in the primary care office if the patient’s tests the patient’s ability to identify eight dif- history or examination of the ferent smells. Each is tested separately. suggests it. In general, , , or The results are combined with the threshold perfume may be used for initial superficial test- test score to give a composite score: ing; however, strong, irritating aromas such as • 0 to 1.75 indicates anosmia ammonia are more appropriate for measuring • 2 to 3.75 severe hyposmia function rather than olfacto- • 4 to 4.75 moderate hyposmia ry nerve function. Also, each nostril should be • 5 to 5.75 mild hyposmia tested separately to ascertain whether the • 6 to 7 normosmia. problem is unilateral or bilateral. For patients over age 65, the score is adjusted upward by one point. The UPSIT Simple smell The “UPSIT” (University of Pennsylvania Trigeminal nerve assessment tests can Smell Identification test, Sensonics, Inc, In addition to olfactory nerve endings, the Haddonfield, NJ) is a scratch-and-sniff test nasal epithelium contains trigeminal (fifth be done in that uses 40 microencapsulated odorants on cranial) nerve endings. While less sensitive to the office cards, which the patient tries to identify. stimulants than the olfactory nerves, trigemi- The test can be administered by the physi- nal nerve endings are important in detecting cian or self-administered by the patient. tactile pressure, , and temperature sensa- Scoring is on a scale of 0 to 40, with 34 to 40 tions in the areas of the mouth, , and nasal indicating normosmia, 26 to 30 moderate cavity. Trigeminal nerve dysfunction can hyposmia, and 6 to 18 anosmia (with an cause alteration in epithelial that allowance for chance). A score of 0 to 5 can affect reception, transmission, or process- indicates a malingerer. The UPSIT offers a ing of information in olfactory receptors.18 dependable indication of normosmia vs Trigeminal nerve function is assessed by the olfactory dysfunction. ability to detect pungent odors, such as mus- tard oil, (used, eg, in hot chili pow- Threshold testing der, spray), and . At our clinic we use the Connecticut Chemosensory Clinical Research Center Laboratory tests for impaired smell (CCCRC) test, which tests both the patient’s Laboratory testing in patients with impaired threshold to detect an odorant and the olfaction is performed to provide clues to a patient’s ability to distinguish between various causative underlying condition. The workup odorants. should include a complete blood count, sedi- The object is to find the weakest concen- mentation rate, blood concentration, tration of butanol that the patient can detect, and blood urea nitrogen, as well as tests of thy- starting with the weakest dilution. At each roid function and antinuclear level.

332 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 4 APRIL 2002 Other tests may be ordered depending on the investigation given to them, because their history and physical findings. previous visits to other physicians may have been frustrating. Imaging Computed tomography (CT) of the nose and ■ TASTE DYSFUNCTION sinuses and MRI of the brain are often required. In our clinic, single-photon emission CT of the Taste and smell are interdependent, and diffi- brain has revealed defects in some patients culty with one is sometimes interpreted as a with anosmia associated with a head injury problem with the other. Loss of taste occurs when CT and MRI studies were negative.19 when there is a disturbance in the or the surroundings of the taste cells.22 Normogeusia ■ TREATMENT OF IMPAIRED SMELL is the name given to normal taste. Loss or impairment of taste can occur in degrees: Drugs • , diminished taste Topical corticosteroids. In patients with • , distorted taste anosmia due to edema from rhinosinusitis or • Aliageusia, altered taste, usually pleasant polyps, topical corticosteroids can bring strik- • Phantogeusia, persistent abnormal taste ing improvement. Their lack of significant in the absence of a stimulus adverse effects with long-term use is impres- • , no taste. sive compared with systemic corticosteroids. Ageusia is rare because of the redundant , decongestants, antihista- and complex anatomic pathways involved. mines. In patients with loss of smell due to However, hypogeusia, dysgeusia, and phanto- bacterial infection, antibiotics (a penicillin or geusia are common. cephalosporin), decongestants, and antihista- mines are useful. Organs of taste sensation Desensitization with the aid of an allergist The taste system detects sweet, sour, bitter, is sometimes indicated if the smell problem is and salty qualities and protects us from ingest- due to . ing possibly harmful substances. Taste recep- Topical steroids tor cells are found in the taste buds, which are can bring Surgery located in the mouth, throat, larynx, and When conservative approaches are not suffi- esophagus. The cells live approximately 10 striking cient, endoscopic nasal and sinus surgery can days and then regenerate.23 improvement produce dramatic changes. Four different cranial nerves (the fifth, seventh, ninth, and tenth) provide the senso- in - or Treating parosmia ry coverage of the and mouth. The polyp-related Parosmia, or aberrant odor perception, pre- trigeminal (fifth cranial) nerve is responsible sents a challenge. Viral infection, rhinitis, for detecting the burning sensation caused by smell loss head trauma, and brain tumors are occasional- peppers and ammonia. This nerve supplies ly the cause, and attending to these problems sensation to the mouth and nose and transmits may resolve the parosmia. When no cause is messages about chemical irritants to the brain. found, anticonvulsive medications (clon- Taste stimulants require salivary secretion azepam, gabapentin) have been helpful. to get to the taste buds. Soluble carrier pro- teins assist in transportation to the receptors. Reassuring the patient In patients with loss of smell following an Causes of taste dysfunction upper respiratory tract viral infection, no Conditions that can to loss of taste effective therapy is available. However, since include: olfactory cells may regenerate with time, from • Aging months to years,20,21 patients can be told that • Inflammation in the mouth their condition may eventually resolve. • Infection that reduces blood flow to the Although not all patients can be helped, tongue and interferes with saliva production they deeply appreciate the attention and and leads to injury of cell receptors

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 4 APRIL 2002 333 SMELL AND TASTE PROBLEMS MANN

• Gastric reflux (a common cause) taste loss and yet testing reveals the presence • Systemic conditions such as diabetes mel- of normal taste. In most of these cases, it is fla- litus, Sjögren syndrome, pernicious anemia, vor that has been impaired. and Crohn disease. is a complete sensory experience Other causes of impaired taste include: arising from ingested stimulant molecules and exposure. Pesticides such as involves taste, smell, texture, and tempera- organochloride compounds and organophos- ture. It is thought that perhaps 75% of flavor phate and carbamate pesticides24 are used sensation is produced by odorants. Thus, widely and can reach taste receptors via air, patients with taste loss complaints require water, or food. Workers who spray material are smell testing. directly exposed, and the general public can be exposed at home or at work by Whole-mouth taste test or drinking water contaminated by pesticides. A whole-mouth taste test is used to assess the The molecules bind to the tongue, and their patient’s ability to detect, identify, and evalu- chemical effects on taste buds and nerve end- ate the intensity of different concentrations of ings can cause hypogeusia or dysgeusia. sweet, sour, salty, and bitter taste solutions. Neurotoxic effects on the brain can result in Flavor can be enhanced by monosodium glu- neuropsychologic difficulties. tamate, a phenomenon referred to as . Drug, metal exposure. Some experts believe umami is a taste distinct can produce a metallic taste.25 Workers from the four traditional . exposed to zinc and copper fumes have com- plained of metallic tastes.26 Drugs such as Spatial taste test antithyroid agents, angiotensin-converting A spatial test is used to assess different areas of inhibitors,27 and certain antibiotics the mouth since localized areas of impairment (clarithromycin) can cause taste complaints can be undetected. A cotton swab dipped in a (TABLE 1).28 special taste solution is placed in different Trauma. Head injury can cause taste areas of the mouth. The throat is evaluated by Patients with impairment, but only 0.5% of head trauma having a patient swallow part of each taste taste loss patients complain of taste loss. Dysgeusia is a solution. The individual is requested to assess more common complaint and is usually the taste quality and intensity. require result of injury to peripheral nerves. Trauma to smell testing the branch of the Flavor discrimination test can result in either ageusia or dysgeusia. A flavor discrimination test is often used to Surgical procedures. Surgery involving evaluate the combination of both taste and the middle can sometimes cause stretching smell sensation. Four different solutions are or sectioning of the nerve, causing taste loss. used, each with a different degree of . Bronchoscopy, laryngoscopy, and tonsillecto- The patient is requested to taste the solutions my can sometimes damage the lingual branch in random order. of the glossopharyngeal nerve, leading to dys- geusia. Operations on the brain can occasion- Electrogustometry ally cause taste alteration if the central gusta- In electrogustometry, weak electrical currents tory pathways are damaged.29 General anes- are delivered to the various fields in thesia itself can cause taste difficulties.30 the mouth cavity. Radiation. Radiation treatment can injure the taste buds, transmitting nerves, and Somatosensory testing salivary glands, resulting in taste dysfunction. Somatosensory tests measure contact detec- tion and spatial acuity thresholds. A patient’s ■ TASTE TESTING contact (pressure) detection threshold is test- ed with Semmes-Weinstein monofilaments, Taste vs flavor which exert a force proportional to their gauge Verification of the specific taste complaint is when applied to a peripheral nerve field. necessary, since many patients complain of Different areas of the mouth are tested.

334 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 4 APRIL 2002 T ABLE 2 Smell and taste centers in the United States California New York Nasal Dysfunction Clinic Clinical Olfactory Research Center University of California, San Diego, Medical State University of New York Health Science Center Center at Syracuse College of Medicine 200 W. Arbor Drive 766 Irving Avenue San Diego, CA 92103-8654 Syracuse, NY 13210

Colorado Ohio Rocky Mountain Taste and Smell Center University of Cincinnati Taste and Smell Center University of Colorado Health Science Center University of Cincinnati College of Medicine 4200 E. Ninth Avenue 231 Bethesda Avenue Denver, CO 80262 Cincinnati, OH 45267-0528

Connecticut Pennsylvania Connecticut Chemosensory Clinical Research Chemosensory Clinical Research Center Center Monell Chemical Center University of Connecticut Health Center 3500 Market Street 263 Farmington Avenue Philadelphia, PA 19104-3308 Farmington, CT 06030 University of Pennsylvania Smell and Taste Center Maryland Hospital of University of Pennsylvania National Institute of Dental Research 3400 Spruce Street National Institutes of Health Philadelphia, PA 19104-4283 NIH Bldg. 10, Room 1N-114 Bethesda, MD 20892 Virginia MCV Smell and Taste Clinic Medical College of Virginia Richmond, VA 23298-0551 In taste impairment due to mouth Oral and nasal somatosensory chemore- prescribed. Only time will tell if the condition infection, an ception can affect taste and olfaction. Intense will improve. stimulation can cause a decrease in taste In cases of dysgeusia and burning mouth dis- antifungal responsiveness.31 order (a condition most prevalent in post- often is menopausal women), tricyclic antidepressants ■ TREATMENT OF IMPAIRED TASTE (which have analgesic properties) and clon- required azepam can be helpful. Clonazepam causes brain Mouth that produce hypogeusia or stem serotonergic descending inhibition, and dysgeusia may necessitate dental therapy and therefore is a valuable aid in these problems. antibiotics. Not infrequently, antifungal ther- apy is required. troches are used ■ REFERRAL TO A SMELL AND TASTE CENTER frequently for this purpose. In patients with gastric reflux, acid pump A number of centers in this country specialize inhibitors such as omeprazole and lansopra- in the diagnosis and management of zole are effective. In cases of exposure to tox- chemosensory problems (TABLE 2). The ins or drugs, elimination of the offending University of Connecticut Health Center, agent often improves the problem. If trauma is which has been treating smell and taste loss the cause, no specific therapy is available, but for more than 19 years, uses a team approach the condition may improve in time with the that starts with smell and taste testing and regeneration of nerve cells. In cases of radia- includes an internist, otorhinolaryngologist, tion or surgical damage, no therapy can be neurologist, and dentist.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 4 APRIL 2002 335 SMELL AND TASTE PROBLEMS MANN

■ REFERENCES 18. Silver WL, Finger TE. The trigeminal system. In: Getchell 1. Schiffman SS. Taste and smell in disease. N Engl J Med TV, Doty RL, Bartoshuk LM, Snow JB, editors. Smell and 1983; 308:1275–1279. Taste in Health and Disease. New York: Raven Press, 1991. 2. Schiffman SS. Taste and smell in disease. N Engl J Med 19. Mann NM, Vento J. A study comparing SPECT with MRI in 1983; 308:1337–1343. patients with anosmia following . In 3. Morrison EE, Costanzo RM. Morphology of the press 2001. . J Comp Neurol 1990; 297:1–13. 20. Henken RI, Comiter H, Fedio P, O’Doherty D. Defects in 4. Deems DA, Doty RL, Settle RG, et al. Smell and taste dis- taste and smell recognition following temporal lobecto- orders, a study of 750 patients from the University of my. Trans Am Neurol Assoc 1977; 102:146–150. Pennsylvania Smell and Taste Center. Arch Otolaryngol 21. Costanzo RM, Graziadei PP. Development and plasticity of Head and Surg 1991; 117:519–528. the olfactory system. In: Finger TE, Silver WL, editors. 5. Costanzo RM, Zasler ND. Head trauma. In: Getchell TV, Doty Neurobiology of Taste and Smell. New York: John Wiley RL, Bartoshuk LM, Snow JB, editors. Smell and Taste in and Sons, 1987:233–250. Health and Disease. New York: Raven Press, 1991:711–730. 22. Christensen CM. Role of saliva in human taste perception. 6. Mott AE, Cain WS, Lafreniere D, Leonard G, Gent JF, In: Clinical management of taste and smell. Neiselman HL, Frank ME. Topical corticosteroid treatment of anosmia Rivlin RS, editors. New York: Macmillan Publishing Co, associated with nasal and sinus disease. Arch Otolaryngol 1986:414. Head Neck Surg 1997; 123:367–372. 23. Beidler LM, Smallman RL. Renewal of cells within taste 7. Jorgensen MB, Buch NH. Studies on the sense of smell buds. J Cell Biol 1965; 27:263–272. and taste in diabetics. Acta Otolaryngol 1961; 53:539–545. 24. Mott AE, Mann NM. Sensory systems: taste. In: Stellman 8. Kallmann FJ, Schonfeld WA, Barrera SE. The genetic JM, editor. Encyclopedia of Occupational Health and aspects of primary eunuchoidism. Am J Ment Defic 1944; Safety. Geneva, Switzerland: International Labour Office, 48:203–236. 1998: 11.22–11.25. 9. Henkin RI, Bartter FC. Studies on olfactory thresholds 25. Kachru DN, Tandon SK, Misra UK, Nag D. Occupational in normal man and in patients with adrenal cortical lead poisoning among silver jewellery workers. Indian J insufficiency: the role of adrenal cortical steroids and Med Sci 1989; 43:89–91. of serum sodium concentration. J Clin Invest 1966; 26. Gordon T, Fine JM. Metal fume fever. Occupat Med 1993; 45:1631–1639. 8:504–517. 10. Henkin RI. Impairment of olfaction and of the tastes of 27. Abu-Hamdan DK, Desai H, Sondheimer J, Felicetta J, sour and bitter in pseudohypoparathroidism. J Clin Mahajan S, McDonald F. Taste acuity and zinc metabolism Endocrinol Metab 1968; 28:624–628. in captopril-treated hypertensive male patients. Am J 11. Davidson TM, Murphy C. Olfactory impairment. West J Hypertens 1988; 1:303S–308S. Med 1993; 159:71–72. 28. Henken RI. Drug-induced taste and smell disorders. 12. Emmett EA. Parosmia and hyposmia induced by solvent Incidence, mechanisms and management related primari- exposure. Br J Ind Med 1976; 33:196–198. ly to treatment of sensory receptor dysfunction. Drug Saf 13. Frye RE, Schwartz BS, Doty RL. Dose-related effects of 1994; 11:318–377. Flavor involves cigarette smoking on olfactory function. JAMA 1990; 29. Della Ferra MA, Mott AE, Frank ME. Iatrogenic causes of 263:1233–1236. taste disturbance: radiation therapy, surgery and medica- taste, smell, 14. Doty RL, Reyes PF, Gregor T. Presence of both odor identi- tion. In: Handbook of Olfaction and Gustation. Doty RL, fication and detection deficits in Alzheimer’s disease. editor. New York: Marcel Dekker, 1995: 785–791. texture, Brain Res Bull 1987; 18:597–600. 30. Mott AE, Leopold DA. Disorders in taste and smell. 15. Chuah MI, Farbman AI. Developmental anatomy of the Otolaryngol Med Clin North Am 1991; 75:1321–1353. temperature olfactory system. In: Doty RL, editor. Handbook of 31. Green B, Lawless H. of somatosensory Olfaction and Gustation. Philadelphia: Marcel Dekker, chemoreception in the nose and mouth. In: Getchell TV, 1995:147–171. Doty RL, Bartoshuk LM, Snow JB, editors. Smell and taste 16. Bloch KJ, Buchanan WW, Wohl MJ, et al. Sjögren’s syn- in health and disease. New York: Raven Press, 1991. drome: a clinical, pathological, and serological study of 62 cases. Medicine (Baltimore) 1965; 44:187–231. ADDRESS: Norman Mann, MD, University of Connecticut 17. Talal N. Sjögren’s syndrome. Bull Rheum Dis 1966; Health Center, 263 Farmington Avenue, MC 1718, Farmington, 16:404–407. CT 06030-2459.