Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center

Smell and taste disorders are common in the general population, yet little is known about their nature or cause. This article describes a study of 750 patients with complaints of abnormal smell or taste perception from the University of Pennsylvania Smell and Taste Center, Philadelphia. Major findings suggest that: chemosensory dysfunction influences quality of life; complaints of taste loss usually reflect loss of smell function; upper respiratory infection, head trauma, and chronic nasal and paranasal sinus disease are the most common causes of the diminution of the sense of smell, with head trauma having the greatest loss; depression frequently accompanies chemosensory distortion; low body weight accompanies burning mouth syndrome; estrogens protect against loss of the sense of smell in postmenopausal women; zinc therapy may provide no benefit to patients with chemosensory dysfunction; and thyroid hormone function is associated with oral sensory distortion. The findings are discussed in relation to management of patients with chemosensory disturbances.     

Future directions in chemosensory research

The past two decades have witnessed phenomenal growth in chemosensory research in the basic sciences and clinical studies. Although chemosensory disorders today are recognized more widely for their marked impacts on QOL and public safety, the increased research focus has yet to translate into significant therapeutic advances for human olfactory or gustatory dysfunction. Nevertheless, it should be expected that active chemosensory research eventually will yield discoveries necessary to generate better treatment options for otolaryngologists and other physicians caring for smell and taste loss patients. As the understanding of chemosensory biology and disease pathophysiology grows, there is great promise that medical science will conquer the frustrating and debilitating health problems posed by olfactory and gustatory dysfunction. Moreover, it is likely that the lessons gained through chemosensory research will apply broadly to a range of human diseases affecting sensory modalities and the central nervous system.     

Initial otolaryngologic assessment of patients with taste and smell disorders

Patients are often referred to otolaryngologists to evaluate dysfunctions of taste or smell. A history and physical examination focused on signs and symptoms of chemosensory disorders, in combination with screening tests for taste and smell function, can quickly and easily delineate the general type and cause of the dysfunction. Several centers for chemosensory disorders referred to in this issue are available for referral to patients who need detailed testing and evaluation. Although treatment options for most taste and smell dysfunctions are limited, by categorizing disorders, we can give the patient an idea of the probable cause and prognosis of the dysfunction.     

Effects of head injury on olfaction and taste

Traumatic events such as motor vehicle accidents, falls, or assaults can lead to dysfunction in olfaction or gustation. Mechanisms of posttraumatic olfactory dysfunction include direct injury to the sinonasal tract or olfactory epithelium, shearing effect on olfactory fibers at the cribriform plate, or brain contusion or intraparenchymal hemorrhage. Posttraumatic gustatory dysfunction is rare, but may occur as a result of direct injury to the tongue, injury to cranial nerves VII or IX, or brain contusion or hemorrhage. Evaluation of head-injured patients presenting with olfactory or gustatory complaints should include a thorough history, including assessment for pre-and posttraumatic chemosensory dysfunction and potential mechanisms of injury, complete head and neck examination including nasal endoscopy and cranial nerve testing, and focused radiographic imaging, usually CT of the sinuses and skull base. Formal olfactory and gustatory testing may be performed using various techniques, although in cases potentially involving litigation, methodologies able to detect malingering should be used. Treatable causes of chemosensory disturbance, most notably conductive olfactory losses caused by chronic rhinosinusitis or nasal obstruction, should be ruled out. In the event of neurosensory deficits, recovery may occur up to 12 to 18 months after the traumatic event. All patients should be counseled regarding the risks of their chemosensory deficits, and given suggestions for appropriate compensatory strategies.     

Measurement of chemosensory function

Although hundreds of thousands of patients seek medical help annually for disorders of taste and smell, relatively few medical practitioners quantitatively test their patients' chemosensory function, taking their complaints at face value. This is clearly not the approach paid to patients complaining of visual, hearing, or balance problems. Accurate chemosensory testing is essential to establish the nature, degree, and veracity of a patient's complaint, as well as to aid in counseling and in monitoring the effectiveness of treatment strategies and decisions. In many cases, patients perseverate on chemosensory loss that objective assessment demonstrates has resolved. In other cases, patients are malingering. Olfactory testing is critical for not only establishing the validity and degree of the chemosensory dysfunction, but for helping patients place their dysfunction into perspective relative to the function of their peer group. It is well established, for example, that olfactory dysfunction is the rule, rather than the exception, in members of the older population. Moreover, it is now apparent that such dysfunction can be an early sign of neurodegenerative diseases such as Alzheimer's and Parkinson's. Importantly, older anosmics are three times more likely to die over the course of an ensuring five-year period than their normosmic peers, a situation that may be averted in some cases by appropriate nutritional and safety counseling. This review provides the clinician, as well as the academic and industrial researcher, with an overview of the available means for accurately assessing smell and taste function, including up-to-date information and normative data for advances in this field.     

Assessment of chemosensory function using electroencephalographic techniques

Electroencephalographic techniques are widely used to provide an objective evaluation of the chemosensory function and to explore neural mechanisms related to the processing of chemosensory events. The most popular technique to evaluate brain responses to chemosensory stimuli is across trial time-domain averaging to reveal chemosensory event-related potentials (CSERP) embedded within the ongoing EEG. Nevertheless, this technique has a poor signal-to-noise ratio and cancels out stimulus-induced changes in the EEG signal that are not strictly phased-locked to stimulus onset. The fact that consistent CSERP are not systematically identifiable in healthy subjects currently constitutes a major limitation to the use of this technique for the diagnosis of chemosensory dysfunction. In this review, we will review the different techniques related to the recording and identification of CSERP, discuss some of their limitations, and propose some novel signal processing methods which could be used to enhance the signal-to-noise ratio of chemosensory event-related brain responses.     

Special characteristics of expert assessment of olfactory and taste disorders]

BACKGROUND: The number of medical expert opinions dealing with smell and taste disorders has continuously increased in recent years. However, an overview of the specific problems and results of those expert opinions has not been published until now. INDIVIDUALS AND METHODS: Olfaction was assessed by multiple subjective tests in 145 individuals with chemosensory dysfunction caused by trauma or occupational and environmental exposures. Additionally, a gustatory test, nasal endoscopy, anterior rhinomanometry, and radiography of the paranasal sinuses were performed. Malignering was diagnosed on a trial of multiple symptoms. Retronasal olfaction was tested using the Güttich gustatory olfaction test. RESULTS: Most of the medical expert opinions have been ordered by professional associations (42%) and insurance companies (28%). Compensation for olfactory dysfunction was claimed after trauma (64%), occupational exposure (23%) rhinosurgical procedures (8%), and laryngectomy (5%). Anosmia or hyposmia was claimed by 66% and 24% of all individuals, respectively. According to the results of the chemosensory tests, 41% of patients suffered from anosmia and 40% had hyposmia. Malignering was registered in 14%. CONCLUSIONS: The study shows that the "characteristic case" is a male in the late fourties, complaining of anosmia initially noticed after an occipital or frontobasal head trauma. The assessment of olfactory deficits related to toxic or chemical occupational exposure is difficult when a latency between the occupational exposure and the onset of chemosensory dysfunction is present. Moreover, interactions between the occupational exposure and nicotine or alcohol abuse must be taken into consideration. Claims for medical liability arose in 3% of the study group after septoplasty and sinus surgery.     

Nutrition and taste and smell dysfunction

Food selection plays a pivotal role in maintaining adequate nutrient intake, thus elucidating drivers of food choice is a meaningful strategy to maintain health and manage disease. Taste and smell are key determinants of food choice and warrant careful consideration. In this review, we first discuss how sensory stimulation influences food selection and metabolism. We then review the evidence regarding the relationship between taste and smell dysfunction and food preferences and selection, with attention given to contexts of certain chronic diseases. We conclude with brief recommendations for the management of chemosensory disorders. While sensory abilities influence food selection, the effect of taste and smell dysfunction on long-term consumption patterns and health status must be considered in light of environment, exposure, and culture.     

Objective screening for olfactory and gustatory dysfunction during the COVID‐19 pandemic: A prospective study in healthcare workers using self‐administered testing

BackgroundSmell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID‐19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID‐19 patients suggests that self‐reported measures are insufficient for capturing patients with chemosensory dysfunction.ObjectivesThe purpose of this study was to quantify the impact of recent COVID‐19 infection on chemosensory function and demonstrate the use of at‐home objective smell and taste testing in an at‐risk population of healthcare workers.MethodsTwo hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self‐administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one‐month follow‐up surveys were completed.ResultsAmong subjects with prior SARS‐CoV‐2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self‐reported smell and taste loss were both strong predictors of COVID‐19 positivity. Subjects with evidence of recent SARS‐CoV‐2 infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was a time‐dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab.ConclusionHealthcare workers with recent SARS‐CoV‐2 infection had reduced olfaction and normal gustation on self‐administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.     

Imaging of chemosensory loss

Clinical assessment of olfactory dysfunction can be challenging. Because olfactory disturbances comprise most chemosensory abnormalities with imaging findings, this article focuses on the imaging of smell disorders. This article reviews the normal imaging appearance of the olfactory apparatus, discusses the respective roles of CT and MRI, provides illustrative imaging of typical pathologic lesions, and discusses a clinically based imaging strategy.     

Surgical management of chemosensory disorders

As additional understanding of the histopathologic basis of chemosensory dysfunction has been achieved, several actual and potential surgical approaches for correction have been devised. These currently include correction of steroid-dependent anosmia and hyposmia due to septal deviation. Posttraumatic anosmia might be correctable in the future. Surgical approaches to dysgeusia are sparse, probably due to a paucity of information on the causes of this disorder.     

Prevalence and causes of severe taste loss in a chemosensory clinic population

Although complete or near-complete olfactory loss has been extensively documented and described, few published reports have documented severe generalized gustatory loss (across qualities and neural fields) with rigorous psychophysical testing, and none have explored the prevalence or causes of such losses in a large clinical population. This study retrospectively reviews our chemosensory clinic's experience of 1,176 patients evaluated for complaints of chemosensory dysfunction in order to address these issues. Our series confirms that despite the complex, bilateral innervation and regenerative capacity of the gustatory system, severe generalized taste loss does occur as a clinical entity, albeit rarely: only 0.85% (n = 10) of our patients evidenced such a deficit, as compared to 32% (n = 371) who were found to have a profound olfactory deficit. Combinations of systemic and/or acute events may underlie many cases of severe taste loss, and in half of our cases, these patients evidenced moderate to complete smell loss as well.     

Trigeminal event-related potentials in patients with olfactory dysfunction

OBJECTIVE: There are mutual interactions between the olfactory and trigeminal systems. The purpose of this study was (1) to assess trigeminal sensitivity using chemosensory event-related potentials (CSERPs) in patients with olfactory dysfunction and (2) to evaluate whether trigeminal ERPs were different with regard to the presence or absence of olfactory ERPs. MATERIALS AND METHODS: Prospective study of 60 patients who presented with olfactory dysfunction (postinfectious olfactory loss: n = 19, posttraumatic olfactory loss: n = 28, and olfactory loss due to idiopathic, or toxic causes: n = 13). All patients were extensively evaluated with an orthonasal olfactory test based on the "Sniffin' Sticks". In addition, chemosensory ERPs were recorded in response to olfactory and trigeminal stimulation. RESULTS: Olfactory/trigeminal ERPs were recorded in 25/60 patients, respectively. Patients with no detectable olfactory ERPs, considered as severely affected, demonstrated an altered trigeminal sensitivity as indicated by an increase in P2 latencies and a decrease in both, P2 and N1-P2 amplitudes compared to patients with detectable olfactory ERPs. A regression analysis showed a negative relation between P2 latencies and the "Sniffin' Sticks"score (r = -0.46, p < 0.001). CONCLUSIONS: Patients with severe olfactory dysfunction demonstrated decreased trigeminal sensitivity as indicated by electrophysiological measures. This study supports the idea of interactions between the chemical senses. Whether altered responses to trigeminal stimulation may be used as a prognostic measure related to recovery from olfactory loss remains to be demonstrated.     

Insight into the mechanisms of olfactory dysfunction by COVID-19

One of the unique symptoms of COVID-19 is chemosensory dysfunction. Almost three years since the beginning of the pandemic of COVID-19, there have been many studies on the symptoms, progress, and possible causes, and also studies on methods that may facilitate recovery of the senses. Studies have shown that some people recover their senses even within a couple of weeks whereas there are other patients that fail to recover chemosensory functions fully for several months and some never fully recover. Here we summarize the symptoms and the progress, and then review the papers on the causation as well as the treatments that may help facilitate the recovery of the symptoms. Depending on the differences in the levels of severity and the locations where the main pathological venues are, what is most effective in facilitating recovery can vary largely across patients and thus may require individualized strategies for each patient. The goal of this paper is to provide some thoughts on these choices depending on the differences in the causes and severity.     

Prevalence and Assessment of Qualitative Olfactory Dysfunction in Different Age Groups

The prevalence of parosmia and phantosmia among 363 chemosensory and nasal/sinus patients was studied, as was the accuracy with which our clinical questionnaire could assess these dysfunctions. We then investigated whether patients with parosmia or phantosmia, matched for odor intensity, perform poorer on odor identification than do patients with no dysosmia. More than 40% of the study group evidenced either parosmia (18.7%) and/or phantosmia (25.6%), a finding that suggests that more attention should be paid by the medical practitioner in addressing qualitative olfactory dysfunction. Furthermore, it appears that assessment of these dysfunctions may aid in differential diagnosis, and that questionnaires can be used with reasonable validity irrespective of the patient's age. Finally, the results imply that parosmia may be reflected in a discrepancy between odor identification and detection.     

Nutritional management of patients with chemosensory disturbances

The effect of a chemosensory disturbance on nutrition and quality of life is not clear and may show individual variance. It is important for the clinician to become sensitive to this relationship and pursue appropriate nutritional management. Nutritional management of an individual with a chemosensory disorder requires nutritional assessment with appropriate dietary intake measurements, dietary and weight history, food behavior questions, and anthropometric measures. A registered dietitian can identify potential nutritional problems and provide guidance for weight control, dietary modification, and use of food-related compensatory mechanisms to maintain the nutritional status and quality of life in the person suffering from chemosensory disturbances.     

Olfactory function in HIV-positive subjects

The aim of this study was to reinvestigate previous reports of chemosensory dysfunction in HIV-positive subjects. Odor thresholds, odor discrimination and odor identification were assessed using the Sniffin' Sticks test battery. Seventy-four HIV-positive patients were tested. According to CDC criteria, 38 subjects were classified as stage A, 10 as stage B and 26 as stage C. None of the subjects exhibited severe cognitive impairment. Compared to normative data all subjects had normal odor identification and discrimination. However, odor thresholds were well below the median of a normal population. There were no significant differences between stage A, B or C subjects. This may be interpreted as indicating that olfactory dysfunction is among the primary deficits of HIV infection and occurs independently of disease stage. These results confirm previous work suggesting that odor thresholds are elevated early in HIV infection whereas a decline in identification and discrimination abilities is correlated with reduced cognitive abilities.     

Olfactory and gustatory disturbances caused by digitalism: a case report

It is known that an overdose of digoxin causes visual disturbance, but the effect on the senses of smell and taste is not known. A case of olfactory and gustatory disturbance caused by digitalism is reported. In a 62-year-old male patient suffering from chronic digitalism, the serum digoxin level rose to 6.0 ng/ml. The patient was diagnosed not only with visual disturbance but also hyposmia and hypogeusia. The patient recovered from visual and chemosensory disturbances after the serum digoxin concentration returned to normal. Because the similarity of intracellular signal transduction between photoreceptor cells and olfactory and/or taste receptor cells is known, it is suspected that the influence of digoxin to chemosensory organs was caused by intermediation of sodium–potassium–adenosine triphosphatase (Na–K–ATPase) of the chemosensory receptor cells.     

Chemosensory event-related potentials to trigeminal stimuli change in relation to the interval between repetitive stimulation of the nasal mucosa

Event-related potentials (ERPs) to olfactory and trigeminal stimuli have been used commonly to evaluate chemosensory dysfunction. The aim of the present study was to investigate how ERPs could be modified by repetitive stimulations of the intranasal trigeminal nerve using 52% v/v CO₂ stimuli for 200 ms periods. Nine subjects were exposed to 6 sessions each during which trains of 16 stimuli were applied. The interval between stimuli was constant for each experiment, but varied between experiments (10, 20, 30, 40, 60, and 90 s). Trigeminal ERPs were obtained from three positions on the skull. Both intensity ratings and ERP amplitudes decreased as the interstimulus interval (ISI) shortened. Specifically, ratings and response amplitudes were most strongly reduced by approximately 30–50% at the shortest ISI used (10 s) and were largest at an ISI of 90 s. The decrease of amplitudes was strongest for the P₄₆ amplitude. Our findings suggest that this may be the result of both habituation and stimulus predictability. We hypothesize that the ISI dependence of chemosensory ERPs may also be a function of an interaction between A_delta and C fibers. Received: 17 April 1998 / Accepted: 29 July 1998