Introduction: Defining Parosmia

Parosmia, while initially confused by researchers with other symptoms of qualitative smell disorders, thankfully has a well-established definition now. Today, scientists define parosmia as the distortion of smell detection in the presence of smell stimuli, unlike phantosmia, where distorted smell detection occurs without any smell stimuli to trigger it. Cases of loss of smell can be classified into two main categories: quantitative and qualitative smell disorders [1]. Cases of quantitative smell disorders mainly present as hyposmia and anosmia and can be diagnosed and managed more easily. Meanwhile, qualitative smell disorders that present mainly as parosmia and phantosmia are areas of research that are more open to interpretation and management by novel methods [2]. Parosmia also has two subtypes of symptoms with cacosmia being the detection of unpleasant smells and euosmia being the detection of pleasant ones [2, 3].

Prevalence

While previous literature calculated the prevalence of smell disorders to be 19.1% of the general population, the same researchers found that the prevalence of parosmia cases was 4–5% [4,5,6,7]. However, the prevalence among older adults may be as high as 62.5% [5, 8]. Regarding the prevalence of these disorders in cases of COVID-19 infections, these statistics were calculated to be up to 75% for smell disorders and up to 45% for parosmia [9, 10]. Among people with smell disorders, up to 35% were found to have symptoms of parosmia [11].

History of Parosmia

Contrary to popular belief, research efforts on parosmia have continued for over a century, with the first paper published on the topic being an 1895 case study investigating three patients with parosmia. The three patients described parosmic smells as “ammonia-like” and “foul.” Recognized as the paper that coined the term parosmia, Tilley’s report paved the way for future otorhinolaryngologists to investigate this qualitative smell disorder. In the report, the author even experimented with different methods to treat the condition, including intranasal stimulants [12].

Following this study, a 1966 article summarizing a series of twentieth-century papers by the Danish researcher Kaj Zilstorff acted as a position paper for parosmia, describing the understanding of its etiology at the time, as well as treatment methods that had been attempted. In his paper, Zilstorff recommends the intranasal administration of 10% cocaine hydrochloride, stating that it effectively cured almost all subjects with parosmia [13]. This finding was replicated by Leopold et al. in 1991, and was deemed an ineffective method for the long-term management of olfactory dysfunction [14, 15].

Etiology of Parosmia

When the etiology of parosmia is investigated, upper respiratory tract infections, traumatic brain injury, sinonasal diseases, neurological and psychiatric disorders, exposure to toxic chemicals, chemotherapy, and surgery come up as the most common causes of the disorder [16,17,18, 19•, 20,21,22, 23••, 24, 25]. Since it has many potential etiologies, it is important to be careful when ruling out all possible etiologies before a decision is made.

Parosmia and COVID-19

For many years following the initial definition of parosmia in 1895, researchers had shifted their focus toward quantitative smell disorders like anosmia, the term for total olfactory loss, putting qualitative smell dysfunctions like parosmia and phantosmia into the background. Following the onset of the COVID-19 pandemic and the ever-increasing number of cases of post-infectious olfactory dysfunction, the addition of the post-COVID manifestation of parosmia helped cause an accumulation of knowledge and new approaches. Although parosmia was already a condition with years of research but limited clinical interventions, the surge in olfactory dysfunction cases following the COVID-19 pandemic made it a well-known condition. The COVID-19 pandemic has caused breakthroughs in understanding smell disorders, including parosmia.

It has been documented that COVID-19 infections account for many changes in the nose and brain that may be responsible for the smell disorders caused by the disease. Recent studies investigating patients after a COVID-19 infection have detected changes in the brain structure and bilateral atrophy of the olfactory bulb which may account for the long-lasting disordered smell symptoms following the infection [26••, 27]. Interestingly, research conducted in Iraq argued that traditional treatment methods like olfactory training and steroids were rarely effective when treating post-COVID parosmia [28]. To solve this problem, a derived olfactory training method by the name “modified olfactory training” was proposed, demonstrating a statistically significant level of effectiveness in the recovery of post-COVID parosmia patients [29,30,31]. While worrying at first, the increased prevalence of parosmia cases with the COVID-19 pandemic gave way to many discoveries in the field of smell disorders, opening treatment opportunities for the wider body of olfactory disorder patients.

Molecular and Physiological Mechanisms Behind Parosmia

After defining and determining the etiology of parosmia, in addition to the clinical studies classifying parosmia as a result of healing from cases of hyposmia and anosmia, there is also an increase in the number of studies arguing that parosmia is a result of changes in the cortical regions of the brain [32,33,34]. Other studies argue that the distortion of olfactory signals is caused by the ephaptic firing of healing neurons that are not yet remyelinated or by the incorrect wiring of glomeruli [2, 35]. While some patients show improvement in the first 1–2 months of the onset of symptoms, the literature regarding parosmia also documents patients that have improved even after 40 years of symptoms [36]. The vastly varying durations in which parosmia patients have had symptoms account for why the qualitative smell disorders require multiple approaches and explanations for classification. This significant variation can also be interpreted as a sign for clinicians to avoid telling patients that “if symptoms do not improve in the first six months, there is little hope that it will improve later,” a piece of advice many patients hear from primary and secondary care providers. Not only is this advice incorrect, but it can also cause the patient to lose hope in the suggested treatment.

Now that parosmia is shown to be triggered by the presence of certain olfactory stimuli, researchers have shifted their focus toward determining which smells and circumstances trigger the symptoms. A study published by Bonfils et al. in 2005, many years before the COVID-19 pandemic, shows that the smells that trigger parosmia the most were the smells of gasoline, tobacco, perfumes, citrus, and chocolate [37]. The chemical basis of parosmia, however, is a post-COVID era phenomenon. Scientists that have worked in this field for years have taken advantage of their previous experiences and observed the post-COVID parosmia process in many people, finally changing the term “parosmia-triggering smells” to “parosmia-triggering chemicals” [38, 39].

At first, 2-furanmethanethiol, the chemical that gives coffee its intense smell, was identified as a parosmia-triggering chemical. Later, it was revealed through gas chromatography that the triggering factors of the disorder were much more than just one smell molecule [38, 39]. Primarily 2-furanmethanethiol, 2-ethyl-3,6-dimethylpyrazine, 3-methyl-2-butene-1-thiol, and 3-mercapto-3-methylbutyl formate were found to be the main factors triggering parosmia [38, 39]. The question as to why the response to these molecules is altered with the onset of parosmia can have many answers, and the question of whether this increase in the sensitivity of the olfactory system to bad smells, when it is typically evolutionarily adapted to prioritize hazardous smells over others, can be explained with the over-firing of receptors resulting from the overhealing of neurons or the damage to the olfactory bulb following alterations to cognitive functions remains unclear [2, 33, 34]. Furthermore, previous studies have shown that long-term and slow-healing anosmia caused by COVID-19 generally impacted patients’ olfactory bulbs, either through direct damage or through reactivity of the olfactory bulbs upstream from the site of the damage [27]. Olfactory bulb damage being present in some patients with post-COVID anosmia and not in others suggests that this might indicate whether the patient will develop parosmia. Similarly, the correlation between olfactory 4 width and the prevalence of smell disorders in post-viral and post-COVID patients may signal that smell disorders may be caused by receptor damage [40,41,42]. Most recently, studies have shown that certain loci in the human genome may affect the likelihood that one may develop post-COVID olfactory dysfunction [43].

Overall, it can be seen in the previous academic literature that anomalies and variations of many factors can lead to olfactory disorders, including anatomical, genetic, receptor-related, and cortical factors, and that this symptom cannot boil down to a single cause [2, 27, 30, 34, 42,43,44].

Evaluating Parosmia

During the COVID-19 pandemic, centers for smell and taste disorders have also started focusing on novel testing methods and smell tests when evaluating anosmia and parosmia. While not all are used in current clinical practices, methods such as surveys, evaluation forms, neurocognitive tests, parosmia-specific odor identification tests, fMRI, MRI, PET/CT, and gas chromatography have all helped smell and taste specialists investigate the chemical basis of smell even more in-depth [38, 45,46,47,48,49,50,51]. The previously mentioned parosmia-specific surveys and tests make it easier for clinicians to keep track of patient progress, and for patients to stay on top of their treatment process. Parosmia-specific smell identification tests like SSParoT make it easier to interpret the change in the patient’s smell perception and relationship with food [48]. In SSParoT, pleasant and unpleasant smells are paired to provide hedonic range and direction values that turn subjective descriptions of parosmia into objective scores [48].

Changes in Quality of Life

As a symptom distorting patients’ olfactory perception, it is not too surprising to read in the academic literature that parosmia changes the quality of life for the worse [52]. Current literature investigating parosmia patients’ quality of life focuses mainly on the patients’ relationships with cooking and eating. Since the sense of smell is known to be a survival mechanism to determine whether a food is edible, the unpleasant distortion of this sense causes patients to view more foods as inedible or harmful [53]. The initial studies investigating the effects of smell disorders on nutrition found that 72% of patients reported a decline in their enjoyment of food [22, 54]. A recent publication also discovered that patients with parosmia experienced greater weight loss than those with other types of olfactory loss. The same study also investigated the effects of smell disorders in cooking and found that people with smell deficits said they “wanted to get through cooking ASAP” more often than people with an intact sense of smell [55]. Patients testifying how their disorder affected them emphasized the psychological effects of losing a sense, with one patient saying they are “grieving for [their] lost senses” [56]. Another study investigating this issue in the UK found that 52.4% of people with olfactory disorders had either depression and/or anxiety, while 62% of the population said that olfactory disorders had an impact on their enjoyment of their everyday lives [36, 57]. In all studies, parosmia patients reported negative impacts on psychological health, well-being, and nutrition [36, 39, 54,55,56,57,58].

Management and Treatment of Parosmia

Inspired by the long recovery periods of parosmic patients with olfactory training, a derived training method called “modified olfactory training” was proposed, where the traditional procedure is upgraded with the addition of new smells and the extension of the training period [29–31]. Compared to the classical method of olfactory training, this novel method resulted in an overall higher level of recovery, making it the new gold standard for the treatment of olfactory disorders [29]. Even with this method, some patients could take up to 6 months to recover, highlighting the importance of extended treatment duration [29, 30].

When the previously mentioned courses of treatment like corticosteroids and olfactory training fail to yield positive results, surgical techniques like “olfactory cleft blocking” may be used as a last resort. In this novel procedure, openings of the olfactory cleft are surgically closed off, completely preventing potentially triggering odorants from reaching the olfactory epithelium [59]. This technique, however, is reserved for managing the condition since it only provides symptomatic relief from parosmia without restoring normosmia.

As parosmia can seriously affect patients’ quality of life, the management strategies of parosmia must also focus on effectively communicating with the patient and making them feel understood. Therefore, establishing uninterrupted communication between the physician, the patient, and the patient’s relatives is of utmost importance when managing parosmia. This is because parosmia patients’ relatives cannot always detect when the patient is going through emotional distress due to their condition, making the situation even worse for the patients. It is also why it is important to evaluate parosmic patients along with a friend or relative. When a patient is asked to smell a pleasant coffee smell and says that it “smells like tar,” the contrasting reaction from their relative enjoying the smell forms the first step in building empathy between the two.

To support both the recovery and the well-being of the patients, the following course of treatment was developed and implemented by me:

  1. 1.

    The patient is asked to fill out a form informing the clinician of their personal situation and the chemicals disturbing them. They are also asked to create a “blacklist” with parosmia-triggering smells and tastes.

  2. 2.

    If the patient does not live alone, a close friend or relative is asked to accompany them to the smell test. They are then asked to smell the same stimuli, and the contrasting reactions help create an “empathy bridge.”

  3. 3.

    The results of the smell evaluations are saved for use during the diagnosis, treatment, and follow-up processes. It is important that the clinician is familiar with the categories of the smell molecules and looks at the test smells as more than just smells but also chemical substances (“chemoparosmic process”).

  4. 4.

    If the patient is found to have vitamin and mineral deficits, rapid weight loss, and malnutrition, vitamin and mineral supplements should be prescribed in addition to the treatment.

  5. 5.

    Additional treatments should be prescribed to patients exhibiting decreased cognitive functions.

  6. 6.

    The modified olfactory training procedure should be explained to the patient in detail with the durations, frequency, and order of training with the different smells.

  7. 7.

    The patients are advised to make the following changes in their lifestyles:

  1. (a)

    Exercising outdoors: Since sweat may trigger parosmia, working indoors may be difficult for patients. Exercising outdoors will minimize detecting parosmia-triggering body odors and help the patient stay active.

  2. (b)

    To improve mood: Increased sunlight exposure is recommended to elevate mood [60].

  3. (c)

    To improve general quality of life: Patients are recommended to maintain a healthy sleep schedule, listen to music every day, and meditate.

Figure 1 illustrates the ideal methods to support the parosmic patient throughout the treatment.

Fig. 1
figure 1

The support algorithm above is utilized in my clinic to support the patient throughout the entire process, both mentally and physically. Not only does the course of treatment help with the symptoms of parosmia, but the other aspects of the process also help correct the neurotransmitter imbalances in the brain

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Phantosmia

Phantosmia, another potential symptom of qualitative smell disorders, involves distorted smell detection in the absence of an olfactory stimulus [1]. The first documented case of phantosmia was reported in a 1988 paper where a patient experiencing olfactory hallucinations was cured through resection of the left olfactory nerve, which was hypothesized to be the origin of the hallucinations [61]. While phantosmia can result from other olfactory dysfunctions, the etiology is not clearly known for idiopathic phantosmia cases, and phantosmia and olfactory hallucinations are common symptoms in patients with schizophrenia and other neurological/psychiatric conditions [16, 62,63,64,65,66]. Such hallucinations have also been linked to traumatic brain injury, radiation therapy, viral infections, surgeries on the nose, and rhinosinusitis [67,68,69,70,71]. Interestingly, a 2013 case study documented a patient with Parkinson’s disease–related phantosmia that reported increased olfactory hallucinations before weather events like storms, leading him to believe that he could forecast the weather [62]. As the symptom cannot be linked to reactions to certain olfactory triggers, methods of evaluation are more limited compared to other smell disorders. These diagnostic methods include survey questions, scales, fMRI, and magnetic resonance spectroscopy [1, 47, 72, 73]. Most recently, the COVID-19 pandemic has caused a surge in the number of patients with phantosmia, most of whom have developed phantosmia symptoms upon recovering from post-COVID anosmia [44, 71, 74]. A 2022 case study on the course of symptoms of post-COVID phantosmia patients has found great variety in the number of days post-COVID that the patients started having phantosmia symptoms, with patients beginning to see symptoms from as little as 10 days and as long as 300 days after the infection [44].

Current management methods for the disorder are mainly medical [15, 75,76,77]. While it was initially proposed by Zilstorff’s 1966 paper to treat qualitative smell disorders with intranasal cocaine hydrochloride, the treatment method is not used at this time, and recent literature has shown that it is not an effective long-term treatment for phantosmia [13, 14]. Other case studies also demonstrated that medications like antipsychotics, anticonvulsants, and antidepressants could relieve the symptoms of patients with idiopathic phantosmia, suggesting that the disorder may be caused by alterations in cortical structures and activity levels in the brain [65, 76, 78, 79]. Since distorted olfaction in phantosmia does not result from any specific stimuli, the disorder is a field of research that is developing slower than other fields of olfactory research, meaning that future work is still needed to help create an effective method for treating it. Figure 2 is a flowchart summarizing the current diagnosis and treatment processes for patients presenting with olfactory hallucinations.

Fig. 2
figure 2

An example treatment algorithm when treating patients with phantosmia

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Conclusion

Parosmia and phantosmia are qualitative olfactory disorders that greatly affect patients’ quality of life. While parosmia causes unpleasant odors in response to triggering odorants like thiols and pyrazines, phantosmia can cause these odors even in the absence of odorant triggers. Although novel treatment methods have caused significant improvements in the treatment of these disorders, especially parosmia, the success rate still is not satisfactory. Future research should prioritize developing more reliable treatment regimens and focus on improving patients’ quality of life.