Phantosmia

Etiology

Although the exact etiology and pathomechanism of phantosmia are unknown, phantosmia has been described in a myriad of conditions, including, but not limited to, traumatic head injury, upper respiratory tract infections, aging, temporal lobe seizures, sinusitis, brain tumors, certain medications, systemic diseases such as hypothyroidism, and certain neurocognitive disorders such as Parkinson disease.[6] Other suggested contributing etiologies discussed in the literature include migraine, psychiatric, and mood disorders such as schizophrenia.[7] 

However, most often, phantosmia is idiopathic.[8] It is helpful to divide phantosmia into two major categories of either peripheral or central causes. Olfactory dysfunction can also be defined by anatomic location as either conductive, sensorineural, or central dysfunction.[5] Central etiologies for phantosmia may include but are not limited to traumatic brain injury, aging, temporal lobe seizures, brain tumors, migraines, and neuropsychiatric disorders, including schizophrenia.[7] 

As described earlier, integration and interpretation of odorants occur in regions of the brain, including the thalamus, hypothalamus, and dorsolateral frontal cortex. Abnormalities in any of these regions may alter olfaction. Sensorineural dysfunction of the olfactory neuroepithelium has been implicated in phantosmia, as has been described by the association with an upper respiratory infection, including COVID-19.[6][9] 

The prevailing peripheral phantosmia pathomechanism includes an insult to the neuroepithelium, followed by spurious reinnervation and resultant erroneous olfactory transmission.[2]

Epidemiology

Phantosmia is a relatively uncommon olfactory disorder, accounting for only 10-20% of olfactory complaints.[10] The prevalence of phantosmia is largely unknown due to many factors, including underestimates with self-reporting, varying testing standards, and population differences.[11] 

Further complicating the matter, and largely due to the plasticity of the olfactory neuroepithelium, olfactory dysfunction varies with age, thereby limiting epidemiologic comparisons. A recent self-reporting survey of 3606 United States adults aged 40 years or older suggested a phantosmia prevalence of 6%, disproportionately affecting females.[12]

A similar study among Swedish adults aged 60 years or older suggested a prevalence of 4.9%.[7] Although the association of phantosmia with many disorders, including epilepsy, schizophrenia, Parkinson disease, depression, and migraines, has been well documented, the mechanism behind these associations remains poorly characterized.[13]

History and Physical

The history and physical for a patient presenting with the chief complaint of phantosmia should start with a full otolaryngologic history and physical exam. Patients with phantosmia will often complain of spontaneously smelling a "burnt" smell when there is no obvious environmental stimulus such as actual burning. Burnt smell is the most commonly reported smell associated with phantosmia, but other smells have been reported, such as feces, rotten, musty, gas, sweet, metallic, or fruity.[7] 

The history should include but is not limited to characterizing the onset and frequency of symptoms, identifying any stimulus involved with the smells, inquiring about how the patient describes the smell, and identifying any exacerbating or relieving factors.

Also, the practitioner should inquire about the following: history of trauma to the head, psychiatric history, systemic conditions, history of chemoradiation, history of head and neck cancer, medications, history of alcohol use, history of tobacco use, history of illicit drug use, environmental exposures, working conditions, allergies, previous surgeries, family history, recent upper respiratory tract infections, history of migraines, and history of seizures.

Asking the patient if they have a history of sinusitis, sinus polyps, sinus surgery, or previous head imaging may also help guide your management.

Evaluation

As stated previously, a thorough history and physical exam can often provide valuable information regarding the underlying etiology of a patient's phantosmia. Nasal endoscopy can be a useful tool if a peripheral cause is suspected, such as chronic sinusitis or nasal polyposis. If no obvious cause is identified, a computed tomography scan (CT) of the paranasal sinuses and magnetic resonance imaging (MRI) of the brain with attention to the olfactory region may be warranted.[2] 

An MRI brain may readily identify certain tumors, masses, or cerebrovascular accidents. In contrast, a CT sinus may reveal underlying chronic sinusitis, nasal polyposis, or a sinonasal mass, any of which may contribute to the underlying phantosmia. When considering the evaluation of olfactory disorders in general, it is best to divide the disorders into two categories: quantitative and qualitative.

Quantitative olfactory disorders include anosmia or hyposmia, where there is a measurable decrease in the sense of smell, whereas qualitative would describe either parosmia or phantosmia as rather a distorted sense of smell that is more difficult to measure via traditional olfactory testing. There are several objective and physiologic tests for evaluating quantitative olfactory disorders; however, there are no reliable, verified tests for qualitative changes in olfaction.[14]

Treatment / Management

Management of phantosmia can be difficult and complex. Little is known about the treatment and management of phantosmia, but the priority would be finding and treating the root cause of the phantosmia. This fact stresses the importance of a thorough workup. Various treatment plans for central causes of phantosmia have been discussed in the literature, including medications such as antipsychotics, anticonvulsants, and antidepressants. For peripheral causes of phantosmia, the goal of treatment would be to inhibit the neuroepithelial receptors in the olfactory mucosa from producing a smell when there is no stimulus present. Methods described in the literature involve applying local anesthetic such as cocaine to the olfactory mucosa or surgically removing the olfactory mucosa.[2]

Studies involving local anesthetic (e.g., cocaine) placed on the olfactory mucosa have not proven to have long-lasting effects.[15] One study described long-lasting relief of phantosmia after unilateral resection of the olfactory mucosa in a small patient subset. In this study, five patients experiencing phantosmia were treated with haloperidol, two of which reported symptomatic improvement. The other three patients were considered to have unilateral peripheral phantosmia, as their symptoms were refractory to the haloperidol trial.(B3)

Laterality of the defective olfactory epithelium was determined by occluding one nostril for a given amount of time, during which the presence of phantosmia was measured. If phantosmia was experienced with one nostril occluded, the contralateral side was chosen for resection of the olfactory mucosa. All three surgical patients experienced long-lasting relief of their phantosmia, two of which exceeded five years on follow-up and 18 months for the third surgical patient.[2] 

Advances in nasal endoscopy have made this method of surgical excision of the olfactory mucosa a safer option; however, it should be noted there are risks such as cerebrospinal fluid (CSF) leaks, bleeding, and damage to surrounding structures (e.g., orbital contents, orbital nerve, anterior ethmoidal artery, carotid artery, sphenopalatine artery, skull base, etc.) that are involved with this surgical intervention. For these reasons, surgery is considered only after medical management has been exhausted and symptomatology results in significant quality-of-life impairment. Many efforts to describe management strategies for long-lasting phantosmia have been undertaken.

A recent systemic review of phantosmia treatments, including antiseizure medications, antipsychotic medications, antimigraine medications, surgical resection of the olfactory mucosa, and transcranial stimulation, suggested variable etiology-dependent outcomes. For example, most patients experiencing phantosmia during migraine headaches reported resolution of phantosmia with migraine prophylaxis. In patients for whom olfactory mucosa resection was employed, most experienced symptomatic relief.

Transcranial stimulation was shown to be very effective in providing short-term relief; however, it failed to provide significant long-term symptom amelioration. Overall, the systemic review suggested that in studies involving root-cause directed treatment of phantosmia (i.e., antimigraine, antipsychotic, antiseizure, or surgical therapy), 23/29 (73.3%) patients experienced long-lasting relief of phantosmia symptoms, as compared to only 14/44 (31.8%) of patients receiving observation only.[14]

Despite the promising evidence shown by these studies, there remains a significant deficit in establishing robust treatment guidelines. Notably, there are no randomized controlled studies nor head-to-head trials comparing phantosmia treatments.[14] (A1)

In summary, the treatment and management of phantosmia are patient and etiology specific. A thorough workup for the root cause of phantosmia will help guide management. There are limited studies regarding the management and treatment of phantosmia; therefore, future studies are warranted.

Differential Diagnosis

• Parosmia 
• Hyposmia 
• Anosmia 
• Brain mass 
• Temporal lobe seizures 
• Schizophrenia 
• Mood disorders 
• Upper respiratory tract infection 
• Nasal or paranasal sinus disease 
• Chronic rhinosinusitis 
• Nasal polyposis 
• Migraine  
• Epilepsy 
• Neurodegenerative disease

Prognosis

Like other qualitative olfactory disorders, phantosmia is associated with a deterioration of olfactory impairment over time.[16] However, compared to other qualitative olfactory disorders (e.g., parosmia), phantosmia is associated with a faster rate of spontaneous recovery.[17]

Although many treatments for phantosmia have been proposed, most treatments have variable effectiveness, with limited evidence of improved outcomes. Traditionally the etiology of phantosmia was thought to be the main determinant of prognosis, where certain etiologies (e.g., traumatic injury) were associated with a worse prognosis than others (e.g., upper respiratory infection). This association, however, is becoming less clear.[18][19] 

Improved prognosis is increasingly believed to be associated with sex, smoking status, and disease severity - with young, non-smoking individuals with severe disease carrying improved prognosis.[18] The improved prognosis in these demographics may be associated with a greater regenerative capacity of the neuroepithelium.[19] 

As described previously, the sine qua non of phantosmia management addresses the underlying cause, after which resolution of olfactory impairments is often achieved.

Complications

Although the practical complications of phantosmia are less pronounced, it may lead to severe adverse outcomes, including social isolation and anhedonia.[20] Depression, anxiety, and other mood-related disorders may develop due to this debilitating disease in some patients. An empathic team approach involving psychiatrists, otolaryngologists, and others is encouraged for all patients in need. Complications may also arise from treatment attempts. Antipsychotics, antimigraine medications, and antiseizure medications are not without side effects.

Finally, as a last resort, surgical intervention with endoscopic excision of olfactory epithelium involves known risks of CSF leak, skull base injury, orbital injury, bleeding, and more. Risk versus benefit analysis should always be discussed with the patient before undergoing treatment. These complications may be exaggerated by the frequent trivialization of symptoms by medical professionals. Olfactory deficits merit similar attention as visual and auditory deficits and should be addressed appropriately to avoid adverse patient outcomes and foster trust within the patient-physician cooperative.