Approach
The first step in evaluating a patient with olfactory loss is to be sympathetic to his or her complaint. Typically, the person has not undergone formal chemosensory testing and the validity of the complaint is often questioned by family and friends, leading to a sense of frustration and isolation. The physician must recognise the impact this loss has on a patient's overall quality of life.
The history helps to determine the aetiology for a patient's loss of smell. Although some form of chemosensory testing is important to verify and quantify the degree of smell loss, it does not provide any specific information as to causation. Testing can offer prognostic information, as those who score more poorly on the test are less likely to recover over time.[26][66] Determining the aetiology contributes to the discussion regarding prognosis.
History
Types and symptoms of olfactory loss
The patient's chemosensory complaint should be defined: whether it includes loss of smell that is partial (hyposmia) or complete (anosmia), and whether it is associated with a taste loss and/or a distorted smell or taste.
A complaint of dysosmia should be defined as to whether it is a parosmia (distorted sense of smell) or phantosmia (smelling odours that are not present). The latter case would suggest an underlying sinus infection.
Dysosmia tends to be much more common when the loss is induced by a viral infection.[22]
It is important to note whether onset of olfactory loss was acute (as occurs after a virus, traumatic insult, toxic exposure [sudden, excessive], surgery) or gradual (as might occur with nasal and sinus disease, neurodegenerative or autoimmune disease, and ageing). A slowly progressive loss might suggest a systemic or neoplastic process. Patients with postviral olfactory loss generally present months to years after the insult. Following head trauma, depending upon the severity of injury, a smell loss may not be noted for some time afterwards, even though the loss would have been immediate. Patients with genetic syndromes will have no recollection of ever being able to smell.
If the olfactory loss fluctuates (for example, in response to a variety of physical or environmental activities), this would suggest an obstructive or conductive loss secondary to nasal inflammation. However, less than 50% of patients with a conductive olfactory loss will report a history of fluctuation.[17]
History of allergies, recurring sinus infections, asthma, or prior nasal or sinus surgery are pertinent, as are details about nasal symptoms such as congestion and discharge.
Taste loss
Typically, patients with an olfactory loss will also complain of a taste loss, not recognising the contribution of odour information towards flavour perception. It is relatively rare to have a true measurable taste loss.[16][62]
Therefore, it is important to ask patients specifically whether they can distinguish salt, sour, sweet, and bitter to determine whether their taste remains intact; they will usually answer in the affirmative (albeit the intensity of these tastes may seem diminished).
Preceding events
The next step is to focus on any antecedent event that may be associated with symptom onset, bearing in mind the more common causes of olfactory loss (i.e., viral upper respiratory episode, head injury, chronic rhinosinusitis).
Olfactory loss that follows head trauma may not become immediately apparent. It may occur following what seems to be a relatively minor head injury, one not easily recalled by the patient. Olfactory loss is more apt to occur after either a frontal or an occipital blow.
Possible exposure to toxic substances should be ascertained.
Concomitant illnesses, medications, and prior surgery
Chronic nasal and sinus disease may cause a loss of smell.
Any associated systemic symptoms or medical conditions (e.g., Alzheimer's disease, Parkinson's disease, granulomatosis with polyangiitis [formerly known as Wegener's granulomatosis], sarcoidosis, Sjogren's disease) that might be causative need to be evaluated.
Inquiry should be made regarding other neurological symptoms, as well as any pertinent family history of neurological or medical disease (e.g., Turner's syndrome, Kallmann's syndrome).
Current and past medications need to be reviewed. Chemotherapeutic agents, several medications (e.g., amfetamines, oestrogen, naphazoline, phenothiazines, prolonged use of nasal decongestants, zinc gluconate nasal spray), and radiotherapy to the head and neck may affect sense of smell.[49][51][52][53]
Olfactory loss commonly occurs following specific neurosurgical and nasal procedures.
Patients with postviral olfactory loss will tend to remember that their problem began following an infection, and will often recall that it was a particularly severe episode.
Physical examination
Head, neck, and nasal examination
A complete head and neck examination focusing on the nose and surrounding structures is required to rule out the possibility of sinonasal pathology.[17]
Chronic nasal and sinus pathology that causes an olfactory loss generally does so by obstructing the nasal vault, thereby preventing access of odorants to the olfactory receptors.
Septal deviation alone is unlikely to cause an olfactory loss.
It is important to determine whether the loss is due to an inflammatory process, since this is the only situation in which therapy will be effective.
If available, anterior rhinoscopy can be used to assess the presence of rhinitis, whether it is allergic, atrophic, infectious, or vasomotor. It may also be used to rule out the presence of nasal polyps. However, anterior rhinoscopy may be normal despite the presence of pathology obstructing the olfactory cleft (e.g., tumours), and therefore is not adequate to rule out a conductive olfactory loss.
If available, endoscopy using a fibre-optic examination to visualise the middle meatus, sphenoethmoidal recess, and nasal vault will provide further information. [Figure caption and citation for the preceding image starts]: Rigid nasal endoscopic examination of a left nasal cavity suggests disease high in the nose (arrow), while the middle meatus seems clear; A = middle turbinate, B = septumFrom the collection of Dr Allen M. Seiden [Citation ends].
In most cases nasal examination will be normal. Exceptions are as follows:
Nasal polyps: a developing polyp is teardrop-shaped; when mature, it resembles a peeled seedless grape. [Figure caption and citation for the preceding image starts]: Examination of the right nasal cavity using rigid nasal endoscopy; a polyp can be seen protruding from the superior meatus (arrow), while the middle meatus is clear; a = middle turbinate, b = superior turbinate, c = septumFrom the collection of Dr Allen M. Seiden [Citation ends].
Brain injury: nasal examination will be normal unless there are other sequelae from the injury. Findings of nasal trauma (such as fracture deviation of the nasal dorsum and a displaced septum) may indicate direct injury to the olfactory cleft, or may be consistent with a coup-contrecoup injury, or may have led to secondary nasal and sinus pathology causing a conductive olfactory loss.
Parkinson's disease: head and neck examination will generally be normal unless other neurological signs of the disease have become apparent - for example, resting tremor (less common in the head and neck but may involve the jaw or lips) or bradykinesia (impaired facial expression, eye movements).[58]
Craniofacial procedures: nasal examination will vary depending upon the extent of surgery on the nose and paranasal sinuses; patient may or may not have external nasal incisions depending upon whether the facial approach was intranasal (endoscopic) or external.
Endoscopic sinus surgery: nasal endoscopy will demonstrate inflammatory disease with oedema, and possible scarring; the olfactory cleft may not be easily visualised, but the nasal vault will generally demonstrate oedema, crusting, or scarring.
Granulomatosis with polyangiitis: nasal examination will demonstrate extensive crusting not only along the nasal septum but also often along the lateral nasal wall; the mucosa is friable and bleeds easily. Patients may present with a nasal septal perforation, and saddle nose deformity may be present.
Sarcoidosis: submucosal nodules appearing slightly yellow in colour may be present along the nasal septum or inferior turbinates. Friable mucosa with crusting and bleeding may be present. Skin lesions, most notably around the nasal alae (lupus pernio), can be seen. Parotid gland, lacrimal gland, and cervical lymph node enlargement may be present.
Sjogren's syndrome: eyes and mouth may appear dry; the nose usually appears normal. Parotid glands may be enlarged or slightly tender.
Sinonasal tumours: nasal examination, particularly with endoscopy, reveals a mass lesion within the nasal cavity. Associated oedema, purulent discharge, polyps, or crusting may be noted. Evidence of extension beyond the confines of the nose may be present, such as surrounding induration, orbital displacement, or proptosis.
Esthesioneuroblastoma: nasal endoscopy will reveal a reddish-grey friable mass within the nasal vault.
Chemosensory testing
A patient's self-report of olfactory loss is unreliable, so some form of chemosensory testing is essential.[67][68] This serves to validate a patient’s olfactory ability and will pick up the rare case of malingering.
Several approaches to olfactory testing have been validated and are available, although some require trained personnel.[62] Chemosensory testing must follow sound psychophysical testing procedures and usually involves identification of specific odours, an assessment of threshold, or the ability to discriminate the presence or absence of an odour.
The University of Pennsylvania Smell Identification Test (UPSIT) is the most widely used test, as it is readily available, does not require trained personnel to administer, and is validated.[65] It consists of 40 microencapsulated odorants on scratch and sniff pads that the patient must identify from a choice of 4 for each. A shorter screening version of this test using only 4 odorants is also available.
For anosmia, patients would achieve 7 to 19 correct results on UPSIT and for hyposmia, 20 to 34 correct results on UPSIT.
Another useful option is Sniffin' Sticks, developed in Germany.[69] While the UPSIT is an odour identification test, Sniffin' Sticks use an identification, threshold, and discrimination test.
Another, more objective test based upon sniff behaviour has been developed at the University of Cincinnati and has been made available for clinical distribution, but it requires administration by office personnel.[70]
If none of these tests are readily available, an alternative screening method referred to as the Alcohol Sniff Test has been developed that uses a standard 70% isopropyl alcohol pad.[71] This may provide at least a preliminary assessment as to whether the patient's sense of smell is truly absent.
It is difficult for patients to measure taste disturbance objectively, so chemical gustometry or electrogustometry testing of the anterior two-thirds and posterior tongue may be performed. However, this is more labour intensive than that for smell. For chemical gustometry, solutions in increasing concentrations are usually applied to the surface of the tongue (with a dropper or a taste strip) with the 4 fundamental tastes: citric acid (sour), glucose (sweet), sodium chloride (salty), and quinine (bitter). In some cases, monosodium glutamate (umami, the fifth taste) may also be tested. Electrogustometry involves the topical application of a weak electrical current onto the tongue, whereby a positive current is perceived as sour-metallic and a negative current as bitter-sweet. This test is easier to administer but cannot separate the 4 taste qualities and is not precise enough for spatial testing.
Radiological evaluation
In the event that the history is non-specific and the nasal examination unremarkable, a full neurological examination using CT or MRI scans should be considered. Plain x-rays are generally of little benefit in the evaluation of olfactory loss. CT and MRI scans are used primarily to rule out the presence of sinonasal or intracranial pathology, and to evaluate and/or confirm the extent of the injury in patients reporting trauma.
CT scans
Provide the clearest detail of both bony and soft tissue anatomy and demonstrate the presence of any underlying inflammatory disease. CT scan facilitates visualisation of the olfactory cleft.[Figure caption and citation for the preceding image starts]: Coronal CT scan demonstrates inflammatory ethmoid disease along with obstruction of the olfactory cleft (arrow)From the collection of Dr Allen M. Seiden [Citation ends].
A CT scan of the paranasal sinuses is indicated if the nasal examination is abnormal, or a thorough nasal examination including endoscopy cannot be performed. The coronal plane is preferred, and contrast is usually not necessary unless a neoplastic process is suspected.[Figure caption and citation for the preceding image starts]: CT scan with coronal view through the anterior ethmoid sinus clearly displays the ostiomeatal complex, with no evidence of disease; the olfactory cleft is patent (arrow)From the collection of Dr Allen M. Seiden [Citation ends].
A CT scan to rule out sinus or intracranial pathology is usually not necessary if:
patient history clearly indicates that an upper respiratory infection (URI) preceded the olfactory loss
a thorough nasal examination including endoscopy is negative, and there are no associated neurological signs or symptoms.
MRI scans
If the history and physical examination do not indicate a probable cause, then the possibility of an undiagnosed intracranial lesion becomes more relevant, albeit still very uncommon. While an intracranial tumour or neurodegenerative disease can cause olfactory loss, it is unusual for such patients to present primarily for olfactory loss. These patients typically develop other symptoms that compel them to visit a physician. An MRI scan with contrast is the procedure of choice to rule out such lesions, and may be indicated in some patients. However, a study that retrospectively evaluated MRI findings in patients presenting with idiopathic olfactory loss found the incidence of pathology to be extremely small, no greater than in the general population.[18] This suggests that the routine use of MRI in patients presenting with idiopathic olfactory loss may not be warranted.
A routine MRI will adequately visualise the anterior cranial fossa, including the olfactory groove.
If special attention is required to visualise the olfactory bulbs (e.g., in the case of a congenital olfactory loss), then this should be discussed with the radiologist to allow for more specialised cuts.
Other diagnostic tests
The routine use of laboratory tests is rarely helpful but may be considered if suggested by the medical history. Any underlying problems will usually have been previously established by past medical examination, but they may need to be explored further if no alternative aetiologies for chemosensory dysfunction are apparent.
Nasal mucosal biopsy (where a small piece of tissue from the lining of the nose is removed and histopathologically analysed for disease) may be useful in confirming differentials. In granulomatosis with polyangiitis, it will show granulomatous inflammation with vasculitis. In sarcoidosis, it will show non-caseating granuloma. In sinonasal tumours, it will show evidence of malignancy.
While certain vitamin and mineral deficiencies such as vitamin B12, zinc, or copper can alter taste or smell function, these cases are extremely rare. Evaluation for such imbalances need not be performed routinely unless clearly indicated by other signs or symptoms, or by history if patients are so predisposed.
Corticosteroids have a potent anti-inflammatory impact on nasal and sinus oedema. A number of studies have demonstrated their ability to reverse (even if temporarily) a conductive loss of smell, while they have no effect if the loss of smell is attributable to another cause.[17][72][73] Therefore, when the history and examination are equivocal (particularly in the case of a viral versus a chronic inflammatory aetiology) and to help verify whether an olfactory loss is conductive, a trial of systemic corticosteroids can be very useful. Topical corticosteroid sprays are much less effective than oral preparations in this regard.[17] The dose of corticosteroid can vary but need not be high. Examples of when oral corticosteroids may be used to confirm diagnosis following olfactory loss include nasal polyps, upper respiratory tract inflammation, and postendoscopic sinus surgery.
While cognitive testing may assist in the diagnosis of Alzheimer's disease, there are no specific diagnostic tests available for Parkinson's disease.
In granulomatosis with polyangiitis, cytoplasmic staining antineutrophil cytoplasmic antibody (C-ANCA) test will be positive.
In sarcoidosis, chest x-rays shows hilar and/or paratracheal adenopathy with predominantly upper lobe bilateral infiltrates.
In Sjogren's syndrome, SS-A and SS-B antibody tests will be positive. Schirmer test will show decreased tear production, and lower lip minor salivary gland biopsy will show lymphocytic infiltration.
In Turner's syndrome, karyotyping will show abnormal X chromosome.
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