Continuing Education Activity
Phantosmia is a qualitative olfactory disorder wherein an odorant is perceived in the absence of an identifiable stimulus. Although phantosmia is most often idiopathic, it may be associated with nasal mucosal abnormalities, migraines, seizures, and neurocognitive or mood disorders. Little is known about the treatment of phantosmia; however, identifying the underlying etiology can help guide the management of this condition. Due to the variable etiology and morbidity of phantosmia, a comprehensive interprofessional approach is indicated in all cases. This activity describes the evaluation and management of phantosmia and highlights the role of the interprofessional team in evaluating and treating patients with this condition.
Objectives:
Review the epidemiology of phantosmia.
Identify the etiologies of phantosmia.
Outline what is available for the current management/treatment of phantosmia.
Describe the prognosis for phantosmia.
Introduction
Phantosmia is a qualitative olfactory disorder wherein an odorant is perceived in the absence of an identifiable stimulus.This is distinct from the closely-related qualitative olfactory disorder, parosmia, wherein an erroneous odorant is perceived in response to an identifiable stimulus.[1]
Phantosmia has other names, including "olfactory hallucinations" or "phantom odors." Olfactory disorders are often classified as being either conductive or sensorineural. Conductive olfactory dysfunction involves obstruction of an odorant from interacting with the olfactory mucosa. Sensorineural dysfunction is a result of impaired transmission or processing of olfactory stimuli.[2]
Other classifications, including central and peripheral, have also been used to describe phantosmia. Peripheral causes of phantosmiaare thought to arisefrom disruption and alteration of the olfactory mucosa and sensory receptors, whereas central phantosmia is believed to originate from aberrant central integration and interpretation.[2]
Phantosmia can have detrimental effects on a patient's quality of life. The sense of smell is a critical component of the enjoyment of life. It is intimately involved with taste, social life, and the ability to perceive potential environmental dangers.
Anatomy and Physiology
The olfactory epithelium is a pseudostratified columnar neuroepithelium at the superior nasal vault, between the septum and middle turbinate.[1]The basal cell layer of the olfactory epithelium contains stem cells, serving as the basis for its regenerative nature. Superficial to the basal layer lie olfactory receptor neurons, which transmit odorant signals through the olfactory nerve with or without inputs from the trigeminal nerve to the central nervous system, lending to odor perception.[3]
Each olfactory neuron expresses a specific G-protein coupled receptor,which, whenbound by odorants, leads to signal transmission through the cribriform plate to the olfactory bulb.[1]Within the olfactory bulb, olfactory nerves of similar converge onto specific glomeruli to synapse with second-order neurons.[4]
Second-order neurons carry olfactory signals within the olfactory tract to primary olfactory cortex structures such as the piriform cortex, rostral entorhinal cortex, and the periamygdaloid cortex. Further processing and integration occur in the secondary and tertiary olfactory networks, comprised of areas including the thalamus, hypothalamus, and dorsolateral frontal cortex.[5]
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 frequencyof symptoms, identifying any stimulus involved with the smells,inquiring about how thepatient 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 oftenprovide 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 brainmay 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 theneuroepithelial receptorsin 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.
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]
In summary, the treatment and management of phantosmia are patient and etiology specific. A thorough workup for the root cause of phantosmia willhelp 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, thesine 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 isencouraged 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.
Deterrence and Patient Education
Mitigating the effects of phantosmia can be difficult due to the lack of treatment options. The debilitating effects of phantosmia may be mitigated by addressing underlying etiologies and employing patienteducation. This is supported by many cases of phantosmia secondary to migraines, seizures, or schizophrenia, resolving with the treatment of the underlying etiology.
The umbrella of olfactory disorders is large, and educating patients on the nature of their particular olfactory disorder can help them differentiate phantosmia from other olfactory disorders. This differentiation can help further guide evaluation and management. Understanding the underlying etiology, if any, of a patient's phantosmia helps the patient in further pursuit of treatment and potential alleviation of symptoms. Phantosmia can be an extremely debilitating disease and severely affect a patient's quality of life. Therefore, healthcare providersshould understand the definition of phantosmia and its etiology, evaluation, and management to educate patients effectively.
Pearls and Other Issues
Phantosmia describes the perception of an odorant in the absence of an identifiable stimulus in the environment.
Classifications of olfactory disorders include conductive, sensorineural, peripheral, and central.
A myriad of etiologies exists for phantosmia. However, idiopathic is the most common.
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.
When history and physical exam are unrevealing for an obvious root cause of phantosmia, imaging in the form of CT sinus or MRI brain with attention to the olfactory region may be helpful.
Treatment is etiology-dependent, and typically medical therapies (i.e., antipsychotics, anticonvulsants, antimigraine medications, etc.) are exhausted before attempting endoscopic surgical excision of olfactory mucosa.
Overall, little is known about phantosmia and its management. Future studies should be directed towardscharacterizing pathomechanisms and treatment strategies.
Enhancing Healthcare Team Outcomes
An interprofessional, team-based approach is always favored when caring for patients with phantosmia. Often patients with phantosmia may see several healthcare providers, such as their primary care provider, otolaryngologist, psychiatrist, neurosurgeon, and neurologist.
Pharmacists, radiologists, nurses, social workers, and several other healthcare professionals may be involved in the care of phantosmia patients. Primary care providers will often play an important role in first identifying and diagnosing phantosmia as well as proper initial workup and referral to other specialists. Therefore, it is important for the primary care provider, as well as all healthcare providers, to recognize the initial signs and symptoms of patients suffering from phantosmia as early as possible.
Otolaryngologists play an important role in diagnosing phantosmia and treating many of its root causes. If a patient presents with phantosmia and is found to suffer from chronic sinusitis, nasal polyps, a sinonasal mass, a skull base mass, or other disease processes that may affect the olfactory epithelium, it is prudent for the otolaryngologist to do a thorough workup through nasal endoscopy and/or imaging studies and then provide treatment as capable. Often otolaryngologists will surgically treat sinonasal disease or work in conjunction with neurosurgery to treat certain skull base masses.
Otolaryngologists would also provide the endoscopic surgical excision of olfactory epithelium for those patients failing medical therapy and seeking that option. Neurologists play an important role in treating many central causes of phantosmia, such as migraines, neurodegenerative disorders such as Alzheimer or Parkinson disease, and temporal lobe seizures.
Finally, psychiatry consultation is indicated in most patients with phantosmia, given the high prevalence of schizophrenia and other mood disorders in this demographic. In summary, a team-based approach is imperative to enhance the long-term outcomes of patients experiencing phantosmia.
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Disclosure: Benjamin Gillette declares no relevant financial relationships with ineligible companies.
Disclosure: Joshua Reid declares no relevant financial relationships with ineligible companies.
Disclosure: Carl Shermetaro declares no relevant financial relationships with ineligible companies.
