Allergy Olfactory
grand rounds loss and allergic rhinitis
Andrea J. Apter, MD, April E. Mott, MD, William S. Cain, PhD, Jeffrey D. Spiro, MD, and Morven C. Barwick, MD Farmington, Corm
Patients’ complaints of olfactory loss are not uncommon to the allergist. Although not a life-threatening condition, chronic impairment can significantly affect an individual’s sense of well-being. Some persons with olfactory loss undergo potentially harmful weight changes and fluctuations in dietary habits. Recently a new mother was admitted for evaluation because she was afraid her inability to detect smoke, escaping gas, or spoiled food would endanger her infant, Whether or not one’s health is jeopardized, the ability to smell is a significant pleasure adding enjoyment to life. The most frequent cause is mechanical obstruction of the airway from congestion or nasal polyps. Although sinusitis in and of itself is not a cause of obstruction of the airway, resulting edema in the ethmoidal sinus and osteomeatal complex can obstruct the tiny olfactory cleft. As a predisposing factor to sinusitis, allergic rhinitis is well-described. ’ However, the impact of allergic rhinitis on sense of smell in the absence of other nasal abnormalities has not been studied extensively. Although improvements in olfaction have been reported after treatment of allergic rhinitis,2, 3 documentation of olfactory loss in controlled studies of patients lacking other nasal disease tends to be lacking. Illustrative of the potential importance of controlling allergic rhinitis for the preservation of olfactory sense is the case of an individual with hyposmia and no evidence of gross mechanical obstruction whose sense of smell dramatically improved with treatment. The pathophysiology, differential diagnosis, and treatment of olfactory loss, especially as it is pertinent to the allergist, is discussed.
From the Department of Medicine, University of Connecticut Health Center and The Connecticut ChemosensoryClinical Research Center, University of Connecticut Health Center, Farmington. Supportedin part by National Institutes of Health grant DCO0168. Reprint requests:Andrea 3. Apter, MD, Department of Medicine, LG-006, University of Connecticut Health Center, Farmington, CT 06030. l/1/40447
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Abbreviations used CAT: Computerized axial tomography
CCCRC: Connecticut ChemosensoryClinical ResearchCenter post-URI: Post upper respiratory infection
CASE PRESENTATION Dr. April E. Mott*: A 33-year-old woman was admitted to the Connecticut Chemosensory Clinical Research Center (CCCRC) for evaluation of diminished sense of smell. The olfactory loss was first noted 1.5 years before the evaluation. At that time, while in the third trimester of her first pregnancy, an upper respiratory infection (URI) developed in the patient. She had symptoms for approximately 10 days, with cough, nasal congestion, purulent rhinorrhea, and low-grade fever present. Postnasal drip persisted for several weeks after the other symptoms resolved. No antibiotics or other medications were prescribed. During this illness the patient noted a complete loss of sense of smell. As her nasal congestion diminished, some smell function returned, but the hyposmia remained. After her daughter’s birth, she began to have parosmias. These parosmias included a fleeting phantom aroma of toast and distortions of coffee perceived as “almost burnt.” There was no accompanying loss of taste (sweet, salty, bitter, or sour). At times her sense of smell would briefly return to normal without specific precipitating events. The patient is a research chemist. Some of her work involves occasional exposure to a variety of solvents that are used under a hood. No coworkers have complained of olfactory loss. After the delivery of her baby she remained on maternity leave for 3.5 months. During this period, despite no contact with chemicals, *Assistant Professor of Medicine, Internist, Medical Director, CCCRC
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her sense of smell did not improve. She has never smoked cigarettes. Nine months after the respiratory tract infection occurred, fiberoptic endoscopy and a computerized axial tomography (CAT) scan of the paranasal sinuses disclosed no abnormality. In particular, no nasal polyps or sinusitis was seen. CAT of the head with contrast revealed no abnormality. Dr. Andrea J. Apter*: The patient lives in the Northeastern United States. The initial respiratory infection occurred in the month of July while she was vacationing in Hawaii. She has no definite history of allergic rhinitis as a child. However, at age 23 years she had a “head cold” in late August and September, which consisted of nasal congestion, clear rhinorrhea, and sneezing, with occasional pharyngeal discomfort. The same symptoms developed the next year and in ensuing years. In April and May similar but milder rhinitis occurred. Cutting grass and dusting produce nasal congestion and clear rhinorrhea. Her sneezing, congestion, and rhinorrhea improve in air-conditioned rooms. She recalls only very limited exposure to cats. Her nasal symptoms are alleviated by oral decongestants and antihistamines. She does not use topical nasal decongestants. Physical examination was remarkable only for prominent congestion of the turbinates without evidence of polyps. The nasal septum was deviated. Dr. Jeffrey D. Spiro$: Fiberoptic endoscopy confirmed the findings of the physical examination and the previous endoscopy. In particular, no obstruction of the olfactory cleft was appreciated. Inspection of the nasal cavities with the nasal speculum and a head mirror or light is an essential initial step in the physical examination of any patient with persistent olfactory loss. Attention should be directed toward structural abnormalities or nasal mucosal changes that might block olfactory stimuli from reaching the olfactory cleft, located in the most superior portion of the nasal cavity. Significant findings include the presence of major nasal septal deformities, nasal polyps, or marked hypertrophic changes of the turbinate mucosa. Examination of the posterior and superior nasal cavity is greatly enhanced by the use of the fiberoptic endoscope. Endoscopic examination provides more detailed information and may reveal abnormalities not visualized by conventional nasal examination. For this ___ * Assistant (‘linkal
Professor of Medicine. hnmunolo~y.
Chief.
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reason, fiberoptic nasal endoscopy 1s a standard part of the otolaryngology evaluation q>f:ill patients with chronic smell loss at the CCCRC. In this patient nasal mucosal congcstrl)n without polyp formation and without obstruction of the olfactory cleft was observed. The hihtoq and skin testing distinguish congestion associated with siirrgic rhinitls from nonallergic rhinitis. Dr. Morven C. Barwick*: Ncurolo~:i~ cxamination was within normal limits; particular :~ttention was paid to the cranial nerves. At the CCCRC, detailed testing of thi* first cranial nerve is carried out by a psychologist as described herein, but under more ordinary circumstances olfaction should be tested separately in each nostril by use of odorants that do not simultaneousi> actlvatc the trigeminal irritant pathway. In assessing the patient who presents with complaints of diminished or absent sense of smell, the examiner must keep in mind the possibility of a structural intracranial icsion such as an olfactory meningioma. The h&tory of 911rnsidious onset of olfactory impairment with or \sithout headache, and the absence of local intranasal ;~bnormalitie~ should bring to mind such a considerari~~n. Dr. Mott: Three oral/ nasal chemoicn\ory qstems exist: dfaction (smell), gustatio~ Crastc).and the ~YVTZmot7 chemic~ul sense (irritation or pungency ) Flavor perception results from stimulation cotthvsd three systerns, with olfaction commonly playing the major role.’ ’ Olfactory loss, therefore. i‘; often perceived as flavor reduction as well as dirnmishcd &f&ion. Patients often misconstrue this loss of flavor as “taste” loss.“.” Absent taste (ageusia) or tliminished taste (hypogeusia) is only present if the patieni s ability to detect sweet, sour, salty, or hitte: 13 impaired. Assessment of olfactory function i5 *~metimes complicated by the common chemical sI.:nst’. In addition to olfactory information transmitted hy the first cranial nerve, the trigeminal componenrs (irritating properties of odorants) are transrmtted via tree nerve endings of the trigeminal nerve. Some pdticnts crroneously report retained olfactory functiori when they can detect pungency of odorants or$. Dr. William S. Cain*: Olfactory testing. which has been described in detail elsewhere.’ consists of two parts at the CCCRC. The first comprises threshold evaluation with use of n-butyl alcohol in an aqueous concentration series ranging from 2 ,< Ii) tct 3%. The patient is given in double-bfir;dcd ::V&KW tu#o
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FIG. 1. Patient taking threshold BA, 1992.)
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plastic squeeze-bottles containing either water or a concentration of butanol (Fig. 1). The patient is asked to specify the stronger odor, and the correct choice at a given concentration five times in a row defines the threshold. Pop-up spouts on the bottles permit each nostril to be tested separately. The threshold concentration is translated into a numeric score ranging from 0 to 7, with 7 indicating normal to above average butanol detection and 0 severely impaired to no detection. The second part of the evaluation entails odor identification. Seven common odors are tested: chocolate, coffee, baby powder, mothballs, peanut butter, Ivory soap, and cinnamon. A trigeminal stimulus, Vick’s Vapo-Steam (Richardson-Vicks, Inc., Shelton, Conn.) is also tested. As with the previous test, each nostril is tested separately. The patient is provided with a list of 16 odor names from which to choose a response. If an incorrect response is given, the patient is corrected and the odor is presented again later in the test. This minimizes test bias for variations in odor familiarity based on previous experience. In this test 7 is also a maximum score. The final score is achieved by averaging the results
Test. (Courtesy
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Penny Z. Apter,
of the two tests. A score of 6.0 to 7.0 is considered to represent normosmia, 5.0 to 5.75 mild hyposmia, 4.0 to 4.75 moderate hyposmia, 2.0 to 3.75 severe hyposmia, and 0 to 1.75 anosmia in patients under age 65 years. The patient described in this report was found to be severely hyposmic bilaterally. On the left, the odor threshold score was 4 and the identification score was 0, giving a composite scores of 2.0 on the left. On the right, the odor threshold was 3 and the odor identification was 2, for a composite score of 2.5. Dr. Apter: Skin testing revealed marked immediate hypersensitivity to Dermatophagoides pteronyssinus and D. farinae as well as ragweed. Tests of birch, elm, maple, oak, cat, Alternaria, Aspergillus fumigatus, and Cladosporium also were positive. These results were generally consistent with her history. CLINICAL COURSE Dr. Mott: The initial evaluation revealed no evidence of chronic sinusitis, nasal polyps, or damage to the central olfactory pathways. Thus the differential diagnosis considered by the multidisciplinary team was limited to allergic and nonallergic rhinitis and
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neuroepithelial damage from respiratory tract infection. Three of the patient’s clinical features are consistent with olfactory loss caused by viral respiratory tract infection: (1) the temporal association of smell loss with the infection, (2) the subsequent initial return of some smell function, and (3) the type and timing of her parosmias. Post-upper respiratory viral (post-URI) olfactory loss presumably results from direct viral damage of the olfactory receptors (see herein). If the stem cells are spared, olfactory neurons can regenerate and olfactory function may gradually improve. Gradual improvement, in the absence of treatment, would not be expected in an ongoing, chronic process such as perennial allergic or vasomotor rhinitis. The presence of parosmias is sometimes useful in differential diagnosis, especially if information is available regarding the type, quality, and timing of the parosmias. Distortions of actual odors imply the existence of an intact, albeit often impaired, olfactory system,” whereas phantom smells may be perceived in a disconnected system.” The presence of both phantoms and distortions in this patient suggests a partially disrupted system, a conclusion confirmed by the presence of at least some ability to smell on olfactory testing. Parosmias are often seen in post-URI loss, both coincident with the time of surmised damage, and later corresponding to recovery of olfaction and presumed neuronal regeneration. Had the patient described her parosmias as fecal or foul, it might be suspected that she was perceiving odors arising from the nasal cavities or oropharynx (e.g., purulent sinus drainage) indicative of active infection, an intact system, and therefore potentially reversible local disease. The descriptions provided by this patient of “toast” phantoms and “almost burnt” coffee distortions coincident with some olfactory improvement are signs of a partially recovered. though still impaired, olfactory system. ‘4 clinical characteristic was present, however, that was not consistent with post-URI loss as an exclusive cause: fleeting periods of improved olfactory ability. Such fluctuations are indicative of reversible obstruction in the nasal cavities from rhinitis, nasal polyps, or sinusitis.‘. “’ Fluctuations would not be expected if olfactory loss were due solely to damaged neurons. Dr. Apter: Of note was the patient’s report of “cold symptoms” occurring frequently in August, “congestion” on exposure to dust. and the positive skin tests for seasonal and perennial allergens, all consistent with allergic rhinitis. In addition, it was probable there had been some neuroepithelial damage resulting from the viral infection. However, a viral origin is a diagnosis of’ exclusion, and no effective treatment exists. ” The patient’s history was not particularly characteristic of a nonallergic or vasomotor rhinitis, but
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nonallergic rhinitis, also a diagnnsix o!‘ .:xrlgnl tends to be diagnosed in older individuals.” Durrn~ the aging process. areas of olfactory neuroepithehum are gradually replaced with respiratory epithelium:“ .“ Although damage to the olfactory epitheliurn from viral infections would be expected to accumulate over time. the loss of olfactory neurons through agmg may bc a separate process in that abnormal neuroepithelial cells have been associated with viral olf;lct(rry los\ and replacement of olfactory neuroeprthelial eclls with respiratory epithelium has been linked to ,rgrnf. No known treatment exists ot such ~r11t”l1ioh\. In
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TABLE I. Frequencies olfactory loss
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of causes of
Frequency
Cause
Nasal and sinus disease Head trauma Upper respiratory tract infection Exposure/medication Aging Congenital Anatomic Multiple? Other$ Idiopathic
FIG. 5. Scanning electron micrograph demonstrates dendrites (D), supporting cells, and cell bodies of olfactory neurons (0). Axon processes (arrows) and axon bundles (Ax) can be seen at base of epithelium. Red blood cell x2400.) (From indicated by (r). (Original magnification Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990;297:1-13. By permission.)
particular, zinc therapy, which had been proposed as efficacious, was shown in a double-blind, placebocontrolled study to lack effecLz6 A viral respiratory infection was considered to be of possible consequence in this patient’s case. Despite the potential for regeneration of the olfactory neurons, only 15% of our patients show significant improvement in olfaction on retesting after such viral infections. However, it is likely we see an unusual patient population as a referral center representing what are the most severe and refractory cases. Another interesting caveat is that until recently evidence of allergic rhinitis was not totally eliminated in cases considered to have a viral origin. Indeed some of these patients did have fluctuations in their ability to smell and some symptoms of rhinitis. We are in the process of reviewing these cases to see if any of these patients with a history of a temporally related respiratory infection, but also with symptoms of rhinitis, have reversible olfactory loss from rhinitis. Head trauma. Head trauma frequently results in irreversible olfactory loss; only approximately 8% to
CCCRC n = 758 n. (%I
SUNY* n =427 n. PO.)
217 (28.6%)
122 (29%)
91 (11.8%) 121 (16.0%)
77 (18%) 88 (21%)
3 (0.4%) 116 (15.3%) 34 (4.5%) 176 (23.2%)
11 (3%) 28 (7%) 27 (6%) 12 (3%) 10 (2%) 52 (12%)
*Personalcommunication: StevenR. Youngertob, PhD, SUNY Upstate MedicalCenter,andDonaldA. Leopold,MD, Department of Otolaryngology, HeadandNeckSurgery,JohnsHopkinsUniversity,February,1992. tSevera1of the specificcausesmentionedabove arethoughtto be contributingfactors. $This categoryencompassses variouscausesfor which thereare only one or two patientseach. For exampleat the CCCRC, includedarepatientswith neurologicdeficitsincludingtwo whose smell loss is attributed to cerebrovascular acccidents.A few patientshavecongenitalabnormalitiessuch as Kallman’ssyndrome,and a few have iatrogenicdefectsrelatedto surgery. Examplesfrom SUNY alsoincludepatientswith olfactoryloss associated with iatrogeniccauses.
39% recover.*’ Shearing of the olfactory nerves as they course through the cribriform plate of the sphenoid bone is the presumed mechanism. In this case the trauma was too remote to be a cause of this patient’s problem. The longest reported delay of the onset of olfactory loss after head trauma is 4 months.” The impact of toxic local exposures or ingestions.
No clear history exists of toxic exposure despite the patient’s occupation, and no colleagues have similar complaints. Such exposures, when they occur, may cause permanent damage,** but the impact of such exposures needs further investigation.29 Excess consumption of common toxins such as alcohol, nicotine, and cocaine also has been postulated as a cause of olfactory loss but remains to be studied.“. ‘O Many common medications have been associated with olfactory loss, including certain calcium channel blockers, opiates, and antimetabolites, but the numbers of patients in these reports are limited.” Nasal-sinus disease. In the CCCRC 28.6% of patients with impaired sense of smell documented by olfactory testing have nasal-sinus disease. Of 122 such
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FIG. 6. Low magnification transmission electron micrograph of olfactory epithelium of a 75-year. old man whose anosmia was associated with a viral infection. The junction of the respirator&# epithelium (RE) and the olfactory epithelium (OE) is demonstrated. Goblet cells {G), ciliated celiv (C} of the RE and the nonciliated supporting cells 1.Y) of the OE can be identified. i/cry fei*d dendrites (0) of olfactory neurons are present, and none in this micrograph reach the cpitheliai surface of nasal cavity (MC). No microvillar cells are evident. (Original magnification x 4028 (From Jafek BW, Harman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral #actor ,. dysfunction. Am J Rhino1 1990;4:91-100. By permission.)
patie Its who had endoscopic and imaging examinations, 86% had nasal polyposis and/or chronic sinusitis. These patients have the best prognosis. In awro lximately two thirds, treated medically or sometimes surgically, olfactory testing revealed improvement. * However, these patients generally have gross
mechanical obstruction of the upper airwq J before treatment. To illustrate, Fig. 9 displays the i-1A.f scan of the paranasal sinuses of another paticm demonstrating obstruction of the olfactory cleft from chronic ethmoid sinusitis. The possihlr signQ?cunc~eof’preprcrm~v. I’ i\ of in-
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FIG. 7. Higher magnification of a portion of biopsy of patient shown in Fig. 6. Tissue was just adjacent to that shown in the previous figure. Tip of an olfactory vesicle (V) or receptor is identified. It is one of the few olfactory neurons identified in this patient’s biopsies and one of the rare neurons whose dendrite (0) reaches the surface of the nasal cavity (NC). (Original magnification, x 14,000.) (From Jafek BW, Harman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral olfactory dysfunction. Am J Rhino1 1990;4:91-100. By permission.)
terest that the patient was pregnant when she first became aware of her sensory loss. Rhinitis associated with pregnancy is well described,” although little data exists associating this rhinitis with diminished sense of smell. In approximately 30% of randomly selected pregnant women significant rhinitis occurs.32.” The risk of sinusitis is increased sixfold.3’ Although the rhinitis of pregnancy has been associated with hormonal and blood volume changes during gestation, Schatz and ZeigeP4 have found the most frequent causes to be allergic rhinitis, bacterial rhinosinusitis, and rhinitis medicamentosa. The rhinitis associated with pregnancy is a temporary condition. Allergic rhinitis. The mechanisms by which allergic rhinitis might cause impairment of smell can be hypothesized but are not well studied to date. As more is learned through examination of the normal and ab-
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normal olfactory neuroepithelium and surrounding cells, some of these processes will become clearer. One would expect that mast cell degranulation, an important cellular event in allergic rhinitis, would ultimately affect olfaction. Degranulation results in release of mediators such as histamine, leukotrienes, prostaglandins, and platelet-activating factor. Consequently, plasma leaks from blood vessels and edema develops. Edema of the mucosa from rhinitis may physically distort the neuronal fibers or prevent contact of receptors with the mucosal surface. In addition, the late phase response has been demonstrated to occur in the nasal mucosa in response to IgE-mediated activation of mast cells with antigen challenge.‘5 Inflammatory cells, such as eosinophils that participate in the late phase response, release substances including major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxic protein, which are neurotoxic. The result may be structural changes in the neuroepithelium. We are aware of only one report of a biopsy of the olfactory mucosa in a patient whose smell loss is attributed to allergic or vasomotor rhinitis.22 That biopsy revealed intact olfactory axons, but short cilia were noted. and some cilia were clustered together. In addition, the supporting cells protruded beyond the level of the receptor endings. Change in the quantity and quality of mucus in allergic rhinitis resulting from release of histamine might alter olfaction. Odorant molecules must dissolve in the mucus overlying the olfactory epithelium and traverse the mucus to make contact with receptors on the neuroepithelial cells. Thus the solubility of these molecules may influence perception. ‘I. ” Changes in the mucus may change the solubility of odorant molecules. In addition, the height of the mucous layer and its viscosity may influence odorant molecule diffusion.“. “. ” Thus it would not be surprising to find that allergic rhinitis by itself can cause diminished olfaction. Furthermore, this smell loss would appear to be reversible. Consequently, it is important for allergists to question their patients with allergic rhinitis about olfactory loss. Screening may be performed quickly in the office by testing with the substances of the CCCRC test: baby powder, chocolate, cinnamon, coffee, mothballs, peanut butter, and soap. Improvement may be confirmed by repeating these tests. Smell function also may be assessed by use of The University of Pennsylvania Smell Identification Test, which is commercially marketed as the Smell Identification Test, Sensonics Inc., Haddon Heights, N.J. This test contains 40 scratch and sniff patches of microencapsulated odorant .38 Investigation of allergic rhinitis as a cause of ol-
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FIG. 8. Transmission electron micrograph of olfactory epithelium of a postviral anosmic patient. A degenerating microvillar cell (M) is surrounded by supporting cells /Sj. Degeneration is evident from the pyknotic nucleus (P) and the vesiculated cytoplasm Iv). Apical pole of the cell is being extruded into the nasal cavity (NC). (Original magnification, x 13,866.) (From Jafek BW, Harman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral olfactory dysfunction. Am J Rhino1 1990;4:91-100. By permission.
FIG. 9. CAT scan of a patient with olfactory opacification of the olfactory cleft (arrow).
factory loss leads to other questions. Could nonallergic rhinitis or vasomotor rhinitis contribute to olfactory compromise’? How many individuals, especially young atopic persons with smell loss attributed to a viral respiratory tract infection, have reversible disease such as allergic rhinitis? SUMMARY
AND CONCLUSIONS
Olfactory loss is of importance for allergists to investigate in their patients, because if it is due to either
loss shows
involvement
of ethmoid
sinuses
and
allergic rhinitis or nonallergic rhinitis. it is potentially reversible. One should be sure to consider nasal polyposis and inflammation from chronic sinusitis. especially of the ethmoidal sinuses. Simple screening in the office can be achieved with an odor identitication test of widely available substances as described above. Should there be no response to treatment or if the patient has a history of chronic sinusitis. rccalcitrant nasal polyposis, or previous otolaryngologic procedures, further evaluation including rhinorcop~
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may be required. Recent olfactory loss in the absence of nasal symptoms and in the absence of abnormalities in the nasal cavity should suggest further investigation to look for a more central process. Morphologic investigation with electron microscopy of the olfactory epithelium and the superior nasal cavity is just beginning. The impact of inflammation in this area awaits investigation. REFERENCES 1. Slavin RG. Nasal polyps and sinusitis. In: Middleton
2. 3.
4. 5. 6.
7.
8.
9. 10.
11. 12.
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15. 16. 17. 18. 19.
E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, eds. Allergy, principles and practice, third ed. St. Louis: CV Mosby, 1988:1291-303. Fein BT, Kamin PB, Fein NN. The loss of sense of smell in nasal allergy. Ann Allergy 1966;24:278-83. Doty RL, Snow JB. Olfaction. In: Goldman J, ed. The principles and practice of rhinology. New York: John Wiley, 1987:761-85. Frank ME, Rabin MD. Chemosensory neuroanatomy and physiology. Ear Nose Throat J 1989;68:291-6. Schiffman SS. Taste and smell in disease. N Engl J Med 1983;308: 1275-43. Henkin RI, Larson AL, Powell RD. Hypogeusia, dysgeusia, hyposmia and dysosmia following influenza-like infection. Ann Otol Rhino1 Laryngol 1975;84:672-82. Cain WS, Gent JF, Goodspeed RB, Leonard G. Evaluation of olfactory dysfunction in the Connecticut Chemosensory Clinical Research Center. Laryngoscope 1988;98:83-8. Mott AE. Topical corticosteroid therapy for nasal polyposis. In: Getchell TV, Doty RL, Bartoshuk LM, Snow JB, eds. Smell and taste in health and disease. New York: Raven Press, 1991:553-72. Barwick MC. Neurologic evaluation of taste and smell disorders. Ear Nose Throat J 1989;68:356-61. Scott AE, Cain WS, Leonard G. Nasal/sinus disease and olfactory loss at the Connecticut Chemosensory Clinical Research Center [Abstract]. Chem Senses 1989;14:745. Mott AE, Leopold DA. Disorders in taste and smell. Med Clin North Am 1991;75:1321-53. Chalton R, Mackay I, Wilson R, Cole P. Double-blind, placebo-controlled trial of betamethasone nasal drops for nasal polyposis. BMJ 1985;291:788. Wilson R, Sykes DA, Chan KL, Cole PJ, Mackay IS. Effect of head position on the efficacy of topical treatment of chronic mucopurulent rhinosinusitis. Thorax 1987;42:631-2. Canciani M, Mastella G. Efficacy of beclomethasone nasal drops, administered in the Moffat’s position for nasal polyposis. Acta Paediatr Stand 1988;77:612-3. Scott AE, Cain WS, Clavet G. Topical corticosteroids can alleviate olfactory dysfunction. Chem Senses 1988;13:735. Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990;297: 1- 13. Getchell TV. Functional properties of vertebrate olfactory neurons. Physiol Rev 1986;66:772-818. Anholt RRH. Primary events in olfaction reception. TIBS 1987;12:58-62. Lancet D. Vertebrate olfactory receptor. Annu Rev Neurosci 1986;9:329-55
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20. Lancet D, Pace U. The molecular basis of odor recognition. TIBS 1987;12:63-6. 21. Doty RL, Kimmelman CP. Smell and taste and their disorders. In: Asbury AK, McKhann GM, McDonald WI, eds. Diseases of the nervous system: clinical neurobiology, vol. 1. Philadelphia: WB Saunders, 1986:466-78. 22. Douek E, Bannister LH, Dodson HC. Recent advances in the pathology of olfaction. Proc R Sot Med 1975:68:467-70. 23. Jafek BW, Hartman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral olfactory dysfunction. Am J Rhinology 1990;4:91-100. 24. Nakashima T, Kimmelman CP, Snow JB, Jr. Structure of fetal and adult olfactory neuroepithelium. Arch Otolaryngol 1984;110:641-6. 25. Nakashima T, Kimmelman CP, Snow JB, Jr. Immunohistopathology of human olfactory epithelium, nerve and bulb. Laryngoscope 1985;95:391-6. 26. Henkin RI, Schecter PJ, Friedewald WT, Demets DL, Raff M. A double-blind study of the effects of zinc sulfate on taste and smell dysfunction. Am J Med Sci 1976;272:285-99. 27. Costanzo RM, Becker DP. Smell and taste disorders in head injury and neurosurgery patients. In: Meiselman HL, Rivlin RS, eds. Clinical measurement of taste and smell. New York: Macmillan Publishing, 1986:565-78. 28. Amoore JE. Effects of chemical exposure on olfaction in humans. In: Barrow CS, ed. Toxicology of the nasal passages. Washington DC: Hemisphere Publishing Company, 1986:15590. 29. Cometto-Muniz JE, Cain WS. Influence of airborne contaminants on olfaction and the common chemical sense. In: Getchell TV, Doty RL, Bartoshuk LM, Snow JB, eds. Smell and taste in health and disease. New York: Raven Press, 1991:76585. 30. Frye RE, Schwartz BS, Doty RL. Dose-related effects of cigarette smoking on olfactory function. JAMA 1990;263: 1233-6. 31. Schatz M, Hoffman CP, Zeiger RS, Falkoff R, Mellon M. The course and management of asthma And allergic diseases during pregnancy. In: Middleton E Jr, Reed CE, Ellis EF. Adkinson NF Jr, Yunginger JW, eds. Allergy, principles and practice, third ed. St. Louis: CV Mosby, 1988:1135-6. 32. Mabry RL. Intranasal steroid injection during pregnancy. South Med J 1980;73: 1176-9. 33. Mabry RL. Rhinitis of pregnancy. South Med J 1986;79:46571. 34. Schatz M, Zeiger RS. Diagnosis and management of rhinitis during pregnancy. Allergy Proc 1988;9:545-54. 35. Naclerio RM, Proud D, Togias AG, et al. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med 1985;3 13:65-70. 36. Laffort P, Patte F, Etcheto M. Olfactory coding on the basis of physicochemical properties. Ann NY Acad Sci 1974; 237: 193-208. 37. Getchell TV, Margolis FL. Getchell ML. Perireceptor and receptor events in vertebrate olfaction. Prog Neurobiol 1984;23:317-45. 38. Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 1984;32:489-502.
grand rounds loss and allergic rhinitis
Andrea J. Apter, MD, April E. Mott, MD, William S. Cain, PhD, Jeffrey D. Spiro, MD, and Morven C. Barwick, MD Farmington, Corm
Patients’ complaints of olfactory loss are not uncommon to the allergist. Although not a life-threatening condition, chronic impairment can significantly affect an individual’s sense of well-being. Some persons with olfactory loss undergo potentially harmful weight changes and fluctuations in dietary habits. Recently a new mother was admitted for evaluation because she was afraid her inability to detect smoke, escaping gas, or spoiled food would endanger her infant, Whether or not one’s health is jeopardized, the ability to smell is a significant pleasure adding enjoyment to life. The most frequent cause is mechanical obstruction of the airway from congestion or nasal polyps. Although sinusitis in and of itself is not a cause of obstruction of the airway, resulting edema in the ethmoidal sinus and osteomeatal complex can obstruct the tiny olfactory cleft. As a predisposing factor to sinusitis, allergic rhinitis is well-described. ’ However, the impact of allergic rhinitis on sense of smell in the absence of other nasal abnormalities has not been studied extensively. Although improvements in olfaction have been reported after treatment of allergic rhinitis,2, 3 documentation of olfactory loss in controlled studies of patients lacking other nasal disease tends to be lacking. Illustrative of the potential importance of controlling allergic rhinitis for the preservation of olfactory sense is the case of an individual with hyposmia and no evidence of gross mechanical obstruction whose sense of smell dramatically improved with treatment. The pathophysiology, differential diagnosis, and treatment of olfactory loss, especially as it is pertinent to the allergist, is discussed.
From the Department of Medicine, University of Connecticut Health Center and The Connecticut ChemosensoryClinical Research Center, University of Connecticut Health Center, Farmington. Supportedin part by National Institutes of Health grant DCO0168. Reprint requests:Andrea 3. Apter, MD, Department of Medicine, LG-006, University of Connecticut Health Center, Farmington, CT 06030. l/1/40447
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Abbreviations used CAT: Computerized axial tomography
CCCRC: Connecticut ChemosensoryClinical ResearchCenter post-URI: Post upper respiratory infection
CASE PRESENTATION Dr. April E. Mott*: A 33-year-old woman was admitted to the Connecticut Chemosensory Clinical Research Center (CCCRC) for evaluation of diminished sense of smell. The olfactory loss was first noted 1.5 years before the evaluation. At that time, while in the third trimester of her first pregnancy, an upper respiratory infection (URI) developed in the patient. She had symptoms for approximately 10 days, with cough, nasal congestion, purulent rhinorrhea, and low-grade fever present. Postnasal drip persisted for several weeks after the other symptoms resolved. No antibiotics or other medications were prescribed. During this illness the patient noted a complete loss of sense of smell. As her nasal congestion diminished, some smell function returned, but the hyposmia remained. After her daughter’s birth, she began to have parosmias. These parosmias included a fleeting phantom aroma of toast and distortions of coffee perceived as “almost burnt.” There was no accompanying loss of taste (sweet, salty, bitter, or sour). At times her sense of smell would briefly return to normal without specific precipitating events. The patient is a research chemist. Some of her work involves occasional exposure to a variety of solvents that are used under a hood. No coworkers have complained of olfactory loss. After the delivery of her baby she remained on maternity leave for 3.5 months. During this period, despite no contact with chemicals, *Assistant Professor of Medicine, Internist, Medical Director, CCCRC
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her sense of smell did not improve. She has never smoked cigarettes. Nine months after the respiratory tract infection occurred, fiberoptic endoscopy and a computerized axial tomography (CAT) scan of the paranasal sinuses disclosed no abnormality. In particular, no nasal polyps or sinusitis was seen. CAT of the head with contrast revealed no abnormality. Dr. Andrea J. Apter*: The patient lives in the Northeastern United States. The initial respiratory infection occurred in the month of July while she was vacationing in Hawaii. She has no definite history of allergic rhinitis as a child. However, at age 23 years she had a “head cold” in late August and September, which consisted of nasal congestion, clear rhinorrhea, and sneezing, with occasional pharyngeal discomfort. The same symptoms developed the next year and in ensuing years. In April and May similar but milder rhinitis occurred. Cutting grass and dusting produce nasal congestion and clear rhinorrhea. Her sneezing, congestion, and rhinorrhea improve in air-conditioned rooms. She recalls only very limited exposure to cats. Her nasal symptoms are alleviated by oral decongestants and antihistamines. She does not use topical nasal decongestants. Physical examination was remarkable only for prominent congestion of the turbinates without evidence of polyps. The nasal septum was deviated. Dr. Jeffrey D. Spiro$: Fiberoptic endoscopy confirmed the findings of the physical examination and the previous endoscopy. In particular, no obstruction of the olfactory cleft was appreciated. Inspection of the nasal cavities with the nasal speculum and a head mirror or light is an essential initial step in the physical examination of any patient with persistent olfactory loss. Attention should be directed toward structural abnormalities or nasal mucosal changes that might block olfactory stimuli from reaching the olfactory cleft, located in the most superior portion of the nasal cavity. Significant findings include the presence of major nasal septal deformities, nasal polyps, or marked hypertrophic changes of the turbinate mucosa. Examination of the posterior and superior nasal cavity is greatly enhanced by the use of the fiberoptic endoscope. Endoscopic examination provides more detailed information and may reveal abnormalities not visualized by conventional nasal examination. For this ___ * Assistant (‘linkal
Professor of Medicine. hnmunolo~y.
Chief.
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reason, fiberoptic nasal endoscopy 1s a standard part of the otolaryngology evaluation q>f:ill patients with chronic smell loss at the CCCRC. In this patient nasal mucosal congcstrl)n without polyp formation and without obstruction of the olfactory cleft was observed. The hihtoq and skin testing distinguish congestion associated with siirrgic rhinitls from nonallergic rhinitis. Dr. Morven C. Barwick*: Ncurolo~:i~ cxamination was within normal limits; particular :~ttention was paid to the cranial nerves. At the CCCRC, detailed testing of thi* first cranial nerve is carried out by a psychologist as described herein, but under more ordinary circumstances olfaction should be tested separately in each nostril by use of odorants that do not simultaneousi> actlvatc the trigeminal irritant pathway. In assessing the patient who presents with complaints of diminished or absent sense of smell, the examiner must keep in mind the possibility of a structural intracranial icsion such as an olfactory meningioma. The h&tory of 911rnsidious onset of olfactory impairment with or \sithout headache, and the absence of local intranasal ;~bnormalitie~ should bring to mind such a considerari~~n. Dr. Mott: Three oral/ nasal chemoicn\ory qstems exist: dfaction (smell), gustatio~ Crastc).and the ~YVTZmot7 chemic~ul sense (irritation or pungency ) Flavor perception results from stimulation cotthvsd three systerns, with olfaction commonly playing the major role.’ ’ Olfactory loss, therefore. i‘; often perceived as flavor reduction as well as dirnmishcd &f&ion. Patients often misconstrue this loss of flavor as “taste” loss.“.” Absent taste (ageusia) or tliminished taste (hypogeusia) is only present if the patieni s ability to detect sweet, sour, salty, or hitte: 13 impaired. Assessment of olfactory function i5 *~metimes complicated by the common chemical sI.:nst’. In addition to olfactory information transmitted hy the first cranial nerve, the trigeminal componenrs (irritating properties of odorants) are transrmtted via tree nerve endings of the trigeminal nerve. Some pdticnts crroneously report retained olfactory functiori when they can detect pungency of odorants or$. Dr. William S. Cain*: Olfactory testing. which has been described in detail elsewhere.’ consists of two parts at the CCCRC. The first comprises threshold evaluation with use of n-butyl alcohol in an aqueous concentration series ranging from 2 ,< Ii) tct 3%. The patient is given in double-bfir;dcd ::V&KW tu#o
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FIG. 1. Patient taking threshold BA, 1992.)
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of the CCCRC Olfactory
plastic squeeze-bottles containing either water or a concentration of butanol (Fig. 1). The patient is asked to specify the stronger odor, and the correct choice at a given concentration five times in a row defines the threshold. Pop-up spouts on the bottles permit each nostril to be tested separately. The threshold concentration is translated into a numeric score ranging from 0 to 7, with 7 indicating normal to above average butanol detection and 0 severely impaired to no detection. The second part of the evaluation entails odor identification. Seven common odors are tested: chocolate, coffee, baby powder, mothballs, peanut butter, Ivory soap, and cinnamon. A trigeminal stimulus, Vick’s Vapo-Steam (Richardson-Vicks, Inc., Shelton, Conn.) is also tested. As with the previous test, each nostril is tested separately. The patient is provided with a list of 16 odor names from which to choose a response. If an incorrect response is given, the patient is corrected and the odor is presented again later in the test. This minimizes test bias for variations in odor familiarity based on previous experience. In this test 7 is also a maximum score. The final score is achieved by averaging the results
Test. (Courtesy
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Penny Z. Apter,
of the two tests. A score of 6.0 to 7.0 is considered to represent normosmia, 5.0 to 5.75 mild hyposmia, 4.0 to 4.75 moderate hyposmia, 2.0 to 3.75 severe hyposmia, and 0 to 1.75 anosmia in patients under age 65 years. The patient described in this report was found to be severely hyposmic bilaterally. On the left, the odor threshold score was 4 and the identification score was 0, giving a composite scores of 2.0 on the left. On the right, the odor threshold was 3 and the odor identification was 2, for a composite score of 2.5. Dr. Apter: Skin testing revealed marked immediate hypersensitivity to Dermatophagoides pteronyssinus and D. farinae as well as ragweed. Tests of birch, elm, maple, oak, cat, Alternaria, Aspergillus fumigatus, and Cladosporium also were positive. These results were generally consistent with her history. CLINICAL COURSE Dr. Mott: The initial evaluation revealed no evidence of chronic sinusitis, nasal polyps, or damage to the central olfactory pathways. Thus the differential diagnosis considered by the multidisciplinary team was limited to allergic and nonallergic rhinitis and
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neuroepithelial damage from respiratory tract infection. Three of the patient’s clinical features are consistent with olfactory loss caused by viral respiratory tract infection: (1) the temporal association of smell loss with the infection, (2) the subsequent initial return of some smell function, and (3) the type and timing of her parosmias. Post-upper respiratory viral (post-URI) olfactory loss presumably results from direct viral damage of the olfactory receptors (see herein). If the stem cells are spared, olfactory neurons can regenerate and olfactory function may gradually improve. Gradual improvement, in the absence of treatment, would not be expected in an ongoing, chronic process such as perennial allergic or vasomotor rhinitis. The presence of parosmias is sometimes useful in differential diagnosis, especially if information is available regarding the type, quality, and timing of the parosmias. Distortions of actual odors imply the existence of an intact, albeit often impaired, olfactory system,” whereas phantom smells may be perceived in a disconnected system.” The presence of both phantoms and distortions in this patient suggests a partially disrupted system, a conclusion confirmed by the presence of at least some ability to smell on olfactory testing. Parosmias are often seen in post-URI loss, both coincident with the time of surmised damage, and later corresponding to recovery of olfaction and presumed neuronal regeneration. Had the patient described her parosmias as fecal or foul, it might be suspected that she was perceiving odors arising from the nasal cavities or oropharynx (e.g., purulent sinus drainage) indicative of active infection, an intact system, and therefore potentially reversible local disease. The descriptions provided by this patient of “toast” phantoms and “almost burnt” coffee distortions coincident with some olfactory improvement are signs of a partially recovered. though still impaired, olfactory system. ‘4 clinical characteristic was present, however, that was not consistent with post-URI loss as an exclusive cause: fleeting periods of improved olfactory ability. Such fluctuations are indicative of reversible obstruction in the nasal cavities from rhinitis, nasal polyps, or sinusitis.‘. “’ Fluctuations would not be expected if olfactory loss were due solely to damaged neurons. Dr. Apter: Of note was the patient’s report of “cold symptoms” occurring frequently in August, “congestion” on exposure to dust. and the positive skin tests for seasonal and perennial allergens, all consistent with allergic rhinitis. In addition, it was probable there had been some neuroepithelial damage resulting from the viral infection. However, a viral origin is a diagnosis of’ exclusion, and no effective treatment exists. ” The patient’s history was not particularly characteristic of a nonallergic or vasomotor rhinitis, but
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nonallergic rhinitis, also a diagnnsix o!‘ .:xrlgnl tends to be diagnosed in older individuals.” Durrn~ the aging process. areas of olfactory neuroepithehum are gradually replaced with respiratory epithelium:“ .“ Although damage to the olfactory epitheliurn from viral infections would be expected to accumulate over time. the loss of olfactory neurons through agmg may bc a separate process in that abnormal neuroepithelial cells have been associated with viral olf;lct(rry los\ and replacement of olfactory neuroeprthelial eclls with respiratory epithelium has been linked to ,rgrnf. No known treatment exists ot such ~r11t”l1ioh\. In
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TABLE I. Frequencies olfactory loss
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of causes of
Frequency
Cause
Nasal and sinus disease Head trauma Upper respiratory tract infection Exposure/medication Aging Congenital Anatomic Multiple? Other$ Idiopathic
FIG. 5. Scanning electron micrograph demonstrates dendrites (D), supporting cells, and cell bodies of olfactory neurons (0). Axon processes (arrows) and axon bundles (Ax) can be seen at base of epithelium. Red blood cell x2400.) (From indicated by (r). (Original magnification Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990;297:1-13. By permission.)
particular, zinc therapy, which had been proposed as efficacious, was shown in a double-blind, placebocontrolled study to lack effecLz6 A viral respiratory infection was considered to be of possible consequence in this patient’s case. Despite the potential for regeneration of the olfactory neurons, only 15% of our patients show significant improvement in olfaction on retesting after such viral infections. However, it is likely we see an unusual patient population as a referral center representing what are the most severe and refractory cases. Another interesting caveat is that until recently evidence of allergic rhinitis was not totally eliminated in cases considered to have a viral origin. Indeed some of these patients did have fluctuations in their ability to smell and some symptoms of rhinitis. We are in the process of reviewing these cases to see if any of these patients with a history of a temporally related respiratory infection, but also with symptoms of rhinitis, have reversible olfactory loss from rhinitis. Head trauma. Head trauma frequently results in irreversible olfactory loss; only approximately 8% to
CCCRC n = 758 n. (%I
SUNY* n =427 n. PO.)
217 (28.6%)
122 (29%)
91 (11.8%) 121 (16.0%)
77 (18%) 88 (21%)
3 (0.4%) 116 (15.3%) 34 (4.5%) 176 (23.2%)
11 (3%) 28 (7%) 27 (6%) 12 (3%) 10 (2%) 52 (12%)
*Personalcommunication: StevenR. Youngertob, PhD, SUNY Upstate MedicalCenter,andDonaldA. Leopold,MD, Department of Otolaryngology, HeadandNeckSurgery,JohnsHopkinsUniversity,February,1992. tSevera1of the specificcausesmentionedabove arethoughtto be contributingfactors. $This categoryencompassses variouscausesfor which thereare only one or two patientseach. For exampleat the CCCRC, includedarepatientswith neurologicdeficitsincludingtwo whose smell loss is attributed to cerebrovascular acccidents.A few patientshavecongenitalabnormalitiessuch as Kallman’ssyndrome,and a few have iatrogenicdefectsrelatedto surgery. Examplesfrom SUNY alsoincludepatientswith olfactoryloss associated with iatrogeniccauses.
39% recover.*’ Shearing of the olfactory nerves as they course through the cribriform plate of the sphenoid bone is the presumed mechanism. In this case the trauma was too remote to be a cause of this patient’s problem. The longest reported delay of the onset of olfactory loss after head trauma is 4 months.” The impact of toxic local exposures or ingestions.
No clear history exists of toxic exposure despite the patient’s occupation, and no colleagues have similar complaints. Such exposures, when they occur, may cause permanent damage,** but the impact of such exposures needs further investigation.29 Excess consumption of common toxins such as alcohol, nicotine, and cocaine also has been postulated as a cause of olfactory loss but remains to be studied.“. ‘O Many common medications have been associated with olfactory loss, including certain calcium channel blockers, opiates, and antimetabolites, but the numbers of patients in these reports are limited.” Nasal-sinus disease. In the CCCRC 28.6% of patients with impaired sense of smell documented by olfactory testing have nasal-sinus disease. Of 122 such
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FIG. 6. Low magnification transmission electron micrograph of olfactory epithelium of a 75-year. old man whose anosmia was associated with a viral infection. The junction of the respirator&# epithelium (RE) and the olfactory epithelium (OE) is demonstrated. Goblet cells {G), ciliated celiv (C} of the RE and the nonciliated supporting cells 1.Y) of the OE can be identified. i/cry fei*d dendrites (0) of olfactory neurons are present, and none in this micrograph reach the cpitheliai surface of nasal cavity (MC). No microvillar cells are evident. (Original magnification x 4028 (From Jafek BW, Harman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral #actor ,. dysfunction. Am J Rhino1 1990;4:91-100. By permission.)
patie Its who had endoscopic and imaging examinations, 86% had nasal polyposis and/or chronic sinusitis. These patients have the best prognosis. In awro lximately two thirds, treated medically or sometimes surgically, olfactory testing revealed improvement. * However, these patients generally have gross
mechanical obstruction of the upper airwq J before treatment. To illustrate, Fig. 9 displays the i-1A.f scan of the paranasal sinuses of another paticm demonstrating obstruction of the olfactory cleft from chronic ethmoid sinusitis. The possihlr signQ?cunc~eof’preprcrm~v. I’ i\ of in-
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FIG. 7. Higher magnification of a portion of biopsy of patient shown in Fig. 6. Tissue was just adjacent to that shown in the previous figure. Tip of an olfactory vesicle (V) or receptor is identified. It is one of the few olfactory neurons identified in this patient’s biopsies and one of the rare neurons whose dendrite (0) reaches the surface of the nasal cavity (NC). (Original magnification, x 14,000.) (From Jafek BW, Harman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral olfactory dysfunction. Am J Rhino1 1990;4:91-100. By permission.)
terest that the patient was pregnant when she first became aware of her sensory loss. Rhinitis associated with pregnancy is well described,” although little data exists associating this rhinitis with diminished sense of smell. In approximately 30% of randomly selected pregnant women significant rhinitis occurs.32.” The risk of sinusitis is increased sixfold.3’ Although the rhinitis of pregnancy has been associated with hormonal and blood volume changes during gestation, Schatz and ZeigeP4 have found the most frequent causes to be allergic rhinitis, bacterial rhinosinusitis, and rhinitis medicamentosa. The rhinitis associated with pregnancy is a temporary condition. Allergic rhinitis. The mechanisms by which allergic rhinitis might cause impairment of smell can be hypothesized but are not well studied to date. As more is learned through examination of the normal and ab-
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normal olfactory neuroepithelium and surrounding cells, some of these processes will become clearer. One would expect that mast cell degranulation, an important cellular event in allergic rhinitis, would ultimately affect olfaction. Degranulation results in release of mediators such as histamine, leukotrienes, prostaglandins, and platelet-activating factor. Consequently, plasma leaks from blood vessels and edema develops. Edema of the mucosa from rhinitis may physically distort the neuronal fibers or prevent contact of receptors with the mucosal surface. In addition, the late phase response has been demonstrated to occur in the nasal mucosa in response to IgE-mediated activation of mast cells with antigen challenge.‘5 Inflammatory cells, such as eosinophils that participate in the late phase response, release substances including major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxic protein, which are neurotoxic. The result may be structural changes in the neuroepithelium. We are aware of only one report of a biopsy of the olfactory mucosa in a patient whose smell loss is attributed to allergic or vasomotor rhinitis.22 That biopsy revealed intact olfactory axons, but short cilia were noted. and some cilia were clustered together. In addition, the supporting cells protruded beyond the level of the receptor endings. Change in the quantity and quality of mucus in allergic rhinitis resulting from release of histamine might alter olfaction. Odorant molecules must dissolve in the mucus overlying the olfactory epithelium and traverse the mucus to make contact with receptors on the neuroepithelial cells. Thus the solubility of these molecules may influence perception. ‘I. ” Changes in the mucus may change the solubility of odorant molecules. In addition, the height of the mucous layer and its viscosity may influence odorant molecule diffusion.“. “. ” Thus it would not be surprising to find that allergic rhinitis by itself can cause diminished olfaction. Furthermore, this smell loss would appear to be reversible. Consequently, it is important for allergists to question their patients with allergic rhinitis about olfactory loss. Screening may be performed quickly in the office by testing with the substances of the CCCRC test: baby powder, chocolate, cinnamon, coffee, mothballs, peanut butter, and soap. Improvement may be confirmed by repeating these tests. Smell function also may be assessed by use of The University of Pennsylvania Smell Identification Test, which is commercially marketed as the Smell Identification Test, Sensonics Inc., Haddon Heights, N.J. This test contains 40 scratch and sniff patches of microencapsulated odorant .38 Investigation of allergic rhinitis as a cause of ol-
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FIG. 8. Transmission electron micrograph of olfactory epithelium of a postviral anosmic patient. A degenerating microvillar cell (M) is surrounded by supporting cells /Sj. Degeneration is evident from the pyknotic nucleus (P) and the vesiculated cytoplasm Iv). Apical pole of the cell is being extruded into the nasal cavity (NC). (Original magnification, x 13,866.) (From Jafek BW, Harman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral olfactory dysfunction. Am J Rhino1 1990;4:91-100. By permission.
FIG. 9. CAT scan of a patient with olfactory opacification of the olfactory cleft (arrow).
factory loss leads to other questions. Could nonallergic rhinitis or vasomotor rhinitis contribute to olfactory compromise’? How many individuals, especially young atopic persons with smell loss attributed to a viral respiratory tract infection, have reversible disease such as allergic rhinitis? SUMMARY
AND CONCLUSIONS
Olfactory loss is of importance for allergists to investigate in their patients, because if it is due to either
loss shows
involvement
of ethmoid
sinuses
and
allergic rhinitis or nonallergic rhinitis. it is potentially reversible. One should be sure to consider nasal polyposis and inflammation from chronic sinusitis. especially of the ethmoidal sinuses. Simple screening in the office can be achieved with an odor identitication test of widely available substances as described above. Should there be no response to treatment or if the patient has a history of chronic sinusitis. rccalcitrant nasal polyposis, or previous otolaryngologic procedures, further evaluation including rhinorcop~
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may be required. Recent olfactory loss in the absence of nasal symptoms and in the absence of abnormalities in the nasal cavity should suggest further investigation to look for a more central process. Morphologic investigation with electron microscopy of the olfactory epithelium and the superior nasal cavity is just beginning. The impact of inflammation in this area awaits investigation. REFERENCES 1. Slavin RG. Nasal polyps and sinusitis. In: Middleton
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E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, eds. Allergy, principles and practice, third ed. St. Louis: CV Mosby, 1988:1291-303. Fein BT, Kamin PB, Fein NN. The loss of sense of smell in nasal allergy. Ann Allergy 1966;24:278-83. Doty RL, Snow JB. Olfaction. In: Goldman J, ed. The principles and practice of rhinology. New York: John Wiley, 1987:761-85. Frank ME, Rabin MD. Chemosensory neuroanatomy and physiology. Ear Nose Throat J 1989;68:291-6. Schiffman SS. Taste and smell in disease. N Engl J Med 1983;308: 1275-43. Henkin RI, Larson AL, Powell RD. Hypogeusia, dysgeusia, hyposmia and dysosmia following influenza-like infection. Ann Otol Rhino1 Laryngol 1975;84:672-82. Cain WS, Gent JF, Goodspeed RB, Leonard G. Evaluation of olfactory dysfunction in the Connecticut Chemosensory Clinical Research Center. Laryngoscope 1988;98:83-8. Mott AE. Topical corticosteroid therapy for nasal polyposis. In: Getchell TV, Doty RL, Bartoshuk LM, Snow JB, eds. Smell and taste in health and disease. New York: Raven Press, 1991:553-72. Barwick MC. Neurologic evaluation of taste and smell disorders. Ear Nose Throat J 1989;68:356-61. Scott AE, Cain WS, Leonard G. Nasal/sinus disease and olfactory loss at the Connecticut Chemosensory Clinical Research Center [Abstract]. Chem Senses 1989;14:745. Mott AE, Leopold DA. Disorders in taste and smell. Med Clin North Am 1991;75:1321-53. Chalton R, Mackay I, Wilson R, Cole P. Double-blind, placebo-controlled trial of betamethasone nasal drops for nasal polyposis. BMJ 1985;291:788. Wilson R, Sykes DA, Chan KL, Cole PJ, Mackay IS. Effect of head position on the efficacy of topical treatment of chronic mucopurulent rhinosinusitis. Thorax 1987;42:631-2. Canciani M, Mastella G. Efficacy of beclomethasone nasal drops, administered in the Moffat’s position for nasal polyposis. Acta Paediatr Stand 1988;77:612-3. Scott AE, Cain WS, Clavet G. Topical corticosteroids can alleviate olfactory dysfunction. Chem Senses 1988;13:735. Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990;297: 1- 13. Getchell TV. Functional properties of vertebrate olfactory neurons. Physiol Rev 1986;66:772-818. Anholt RRH. Primary events in olfaction reception. TIBS 1987;12:58-62. Lancet D. Vertebrate olfactory receptor. Annu Rev Neurosci 1986;9:329-55
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20. Lancet D, Pace U. The molecular basis of odor recognition. TIBS 1987;12:63-6. 21. Doty RL, Kimmelman CP. Smell and taste and their disorders. In: Asbury AK, McKhann GM, McDonald WI, eds. Diseases of the nervous system: clinical neurobiology, vol. 1. Philadelphia: WB Saunders, 1986:466-78. 22. Douek E, Bannister LH, Dodson HC. Recent advances in the pathology of olfaction. Proc R Sot Med 1975:68:467-70. 23. Jafek BW, Hartman D, Eller PM, Johnson EW, Strahan RC, Moran DT. Postviral olfactory dysfunction. Am J Rhinology 1990;4:91-100. 24. Nakashima T, Kimmelman CP, Snow JB, Jr. Structure of fetal and adult olfactory neuroepithelium. Arch Otolaryngol 1984;110:641-6. 25. Nakashima T, Kimmelman CP, Snow JB, Jr. Immunohistopathology of human olfactory epithelium, nerve and bulb. Laryngoscope 1985;95:391-6. 26. Henkin RI, Schecter PJ, Friedewald WT, Demets DL, Raff M. A double-blind study of the effects of zinc sulfate on taste and smell dysfunction. Am J Med Sci 1976;272:285-99. 27. Costanzo RM, Becker DP. Smell and taste disorders in head injury and neurosurgery patients. In: Meiselman HL, Rivlin RS, eds. Clinical measurement of taste and smell. New York: Macmillan Publishing, 1986:565-78. 28. Amoore JE. Effects of chemical exposure on olfaction in humans. In: Barrow CS, ed. Toxicology of the nasal passages. Washington DC: Hemisphere Publishing Company, 1986:15590. 29. Cometto-Muniz JE, Cain WS. Influence of airborne contaminants on olfaction and the common chemical sense. In: Getchell TV, Doty RL, Bartoshuk LM, Snow JB, eds. Smell and taste in health and disease. New York: Raven Press, 1991:76585. 30. Frye RE, Schwartz BS, Doty RL. Dose-related effects of cigarette smoking on olfactory function. JAMA 1990;263: 1233-6. 31. Schatz M, Hoffman CP, Zeiger RS, Falkoff R, Mellon M. The course and management of asthma And allergic diseases during pregnancy. In: Middleton E Jr, Reed CE, Ellis EF. Adkinson NF Jr, Yunginger JW, eds. Allergy, principles and practice, third ed. St. Louis: CV Mosby, 1988:1135-6. 32. Mabry RL. Intranasal steroid injection during pregnancy. South Med J 1980;73: 1176-9. 33. Mabry RL. Rhinitis of pregnancy. South Med J 1986;79:46571. 34. Schatz M, Zeiger RS. Diagnosis and management of rhinitis during pregnancy. Allergy Proc 1988;9:545-54. 35. Naclerio RM, Proud D, Togias AG, et al. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med 1985;3 13:65-70. 36. Laffort P, Patte F, Etcheto M. Olfactory coding on the basis of physicochemical properties. Ann NY Acad Sci 1974; 237: 193-208. 37. Getchell TV, Margolis FL. Getchell ML. Perireceptor and receptor events in vertebrate olfaction. Prog Neurobiol 1984;23:317-45. 38. Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 1984;32:489-502.
