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The Nose Knows… or Does it? Olfactory Reference Syndrome in Patients Presenting for Assessment of Unusual Body Odor

McNiven, Vanda, MD*; Mamane, Sarah, MD; Zai, Gwyneth, MD, PhD; So, Joyce, MD, PhD†‡§

The Journal of Nervous and Mental Disease: March 2019 - Volume 207 - Issue 3 - p 145–151
doi: 10.1097/NMD.0000000000000933
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Olfactory reference syndrome (ORS) is a rarely diagnosed psychiatric disorder in which individuals falsely believe that they emit an offensive body odor. This retrospective cohort study characterizes the clinical and demographic features of 54 individuals who presented to a Canadian genetics clinic for query trimethylaminuria (TMAU), an inherited disorder in which a pungent fishy odor is produced. The majority (83%) were found to have a likely diagnosis of ORS and a high rate (73.3%) of concomitant psychiatric disorders; only two patients were diagnosed with TMAU. This study highlights the genetics clinic as an unexpected and major ascertainment point for ORS, and shows that ORS can be differentiated from TMAU by age of onset (~28 years), odor characterization (refuse-related), and the presence of associated comorbid psychiatric diagnoses. There is a low diagnostic rate of ORS, attesting to the need for improved education and awareness.

*Division of Clinical and Metabolic Genetics, The Hospital for Sick Children;

The Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital;

Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto; and

§Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Send reprint requests to Joyce So, MD, PhD, The Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, 60 Murray St, Toronto, Ontario, Canada M5T 3L9. E-mail: joyce.so@utoronto.ca.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jonmd.com).

Olfactory reference syndrome (ORS) is a psychiatric disorder characterized by a preoccupation with the false belief that one emits a foul or offensive body odor (Phillips and Menard, 2011). It was first described by Pryse-Phillips (1971) and has long been reported as a cultural phenomenon (i.e., jikoshu-kyofu) in Japan and Korea (Lim and Ajay, 2012; Lim and Wan, 2015; Suzuki et al., 2004). Individuals with ORS frequently exhibit marked distress and functional impairment at work and in social settings as a result of their perceived foul body odor and the time-consuming rituals that they often engage in to mask or fix the perceived odor (Begum and McKenna, 2011; Bizamcer et al., 2008; Greenberg et al., 2016; Michael et al., 2014; Prazeres et al., 2010; Miranda-Sivelo et al., 2013; Phillips and Menard, 2011). Despite the significant distress and impairment associated with ORS, empirical research on this condition remains scarce (Greenberg et al., 2016). The prevalence of ORS is unknown, and it is likely underdiagnosed due to patient stigmatization and lack of physician awareness.

ORS remains unlisted in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), in part due to the ongoing debate regarding its specific classification and the overlap of its clinical features with several psychiatric disorders, including obsessive-compulsive disorder, body dysmorphic disorder, and delusional disorder (American Psychiatric Association, 2013; Begum and McKenna, 2011; Bizamcer et al., 2008; Greenberg et al., 2016; Luckhaus et al., 2003). Although ORS does not appear as a distinct diagnosis in the DSM-5, it is mentioned under the “Other Specified Obsessive Compulsive Disorders” category as jikoshu-kyofu, a variant of taijin kyofusho (a mental disorder where one fears that one's body, or its functions, is offensive to others; American Psychiatric Association, 2013). The “DSM-5 Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic, and Dissociative Disorders Workgroup” has highlighted the importance of studying ORS (Feusner et al., 2010).

Patients with ORS commonly seek medical attention for an organic diagnosis, such as trimethylaminuria (TMAU), to explain their perceived odors (Ramos et al., 2013). TMAU, often referred to as fish odor syndrome, is a rare, inherited metabolic disorder in which the body is unable to break down trimethylamine, a chemical compound that has a pungent odor resembling that of rotten fish (Mitchell and Smith, 2001). The distinct odor is generally recognized from infancy or early childhood.

To delineate diagnostic criteria and the best treatment options for ORS, it is key to first comprehend its demographic and clinical characteristics. The current study leverages the unique opportunity of investigating these features in a large patient cohort who meet the definition of ORS, and who presented to a Canadian adult genetics clinic seeking clinical assessment for TMAU. A comparison of our study cohort with others in the literature contributes to the emerging body of knowledge on the demographic and diagnostic features of ORS, and highlights the need for awareness of this often debilitating diagnosis in primary care and specialty clinics.

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METHODS

Data Collection

A retrospective chart review was performed for patients seen at The Fred A. Litwin Family Centre in Genetic Medicine at the University Health Network (UHN; Toronto, Ontario, Canada) for query TMAU from January 1, 2010, to January 13, 2017. The study was approved by the UHN research ethics board. Patients were identified from a database of all referrals made to the genetics clinic using the keywords “trimethylaminuria,” “TMA,” “TMAU,” or “odor.” Medical and psychiatric history was collected for each patient to determine whether the patient's findings were consistent with ORS (based on ongoing perceived offensive body odor not ascertained at clinical assessment and inconsistent with the presentation of TMAU or other inborn errors of metabolism). The data were independently reviewed by three members of the study team (S. M., G. Z., J. S.) to reach a consensus for each patient on whether the findings were consistent with a possible or likely diagnosis of ORS. A psychiatrist (G. Z.) also reviewed the clinical data for symptoms suggestive of psychiatric diagnoses that were otherwise not reported by the patients.

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Statistical Analysis

Descriptive statistics were conducted to assess the data for normality and completeness, and to calculate basic and descriptive statistics such as prevalence. Student's t-tests for continuous variables and chi-squared tests for categorical variables were used to compare group differences. Statistical analysis was completed using Microsoft Excel (version 16.12) and GraphPad Software (https://www.graphpad.com/quickcalcs/).

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RESULTS

Demographics of the Study Cohort

In the total study cohort (n = 54), the majority of individuals were female (59%), and the age of onset of reported symptoms was similar between the two sexes (females [F] 27.5 ± 13.8 years, males [M] 25.2 ± 11.7 years; p = 0.5232, t = 0.6429; see Supplemental Table 1 for patient demographics, http://links.lww.com/JNMD/A56). Females were significantly older than males at presentation for genetic assessment (F 42.2 ± 11.4 years, M 34.4 ± 13.8 years; p = 0.0269, t = 2.2770). The majority of individuals identified their ethnicity as European (38.9%), Asian (24.1%), Caribbean (18.5%), and African (14.8%). The consensus diagnoses in the study cohort are shown in Figure 1. Only two patients (3.7%) were diagnosed with TMAU. The majority (83.3%) had a possible or likely diagnosis of ORS, whereas the remainder had other diagnoses to account for their odors.

FIGURE 1

FIGURE 1

Likely or possible ORS patients (n = 45) were predominantly female (62%; Fig. 1). There were no significant differences between the sexes for age at symptom onset (F 28.1 ± 13.9 years, M 28.1 ± 11.4 years; p = 0.9998, t = 0.0003) or at presentation to the genetics clinic (F 41.9 ± 11.9 years, M 36.3 ± 13.3 years; p = 0.1477, t = 1.4741). The majority of individuals identified their ethnicity as European (35.6%), Asian (24.4%), Caribbean (17.8%), and African (15.6%). There were no significant differences in reported ethnicities in our ORS cohort compared with the general population in the Greater Toronto Area.

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Characteristics of the Study Cohort Subset With Likely/Possible ORS

Figure 2 summarizes the odor detection and characteristics reported by individuals with likely or possible ORS (n = 45). The majority of individuals in our ORS cohort self-detected their odor (56%) and perceived that the indirect comments and actions of others were in reference to their odors (68.9%; Fig. 2A). In contrast, only 13.3% of ORS patients reported that others had confirmed that they detected the purported odor through direct comments or when questioned. The number of descriptive terms used for the reported odors ranged from one to six, with an average number of 2.31 (±1.29 SD). The most common odor descriptors (Fig. 2B) were “fecal/sewage” (44.4%), “fishy” (35.6%), “garbage” (31.1%), and “bad/pungent” (24.4%). Common locations from which the odors reportedly arose (Fig. 2C) included “body” (64.4%), “breath” (31.1%), “urine” (20%), and “sweat” (17.8%). Commonly reported odor triggers (Fig. 2D) included foods (42.2%), stress (22.2%), menses (22.2%), and sweating (20%). There was no significant difference between the sexes in any of these variables (other than menses as a trigger).

FIGURE 2

FIGURE 2

The frequency and types of psychiatric diagnoses in the ORS subset are shown in Figure 3. Just over half of individuals (51.1%) reported psychiatric diagnoses, with clinical phenotyping on chart review suggesting additional psychiatric diagnoses to increase the affected ORS subset to 73.3% (Fig. 3A). Of those with self-reported psychiatric diagnoses (n = 23), the most common were anxiety (69.6%) and mood (43.5%) disorders (Fig. 3B). With additional diagnoses based on clinical phenotyping by a psychiatrist (n = 33), the most common diagnoses were anxiety (48.5%), delusional (36.4%), mood (30.3%), and somatoform (21.2%) disorders (Fig. 3B). Figure 3C shows the frequency of ORS patients with single or multiple psychiatric diagnoses. The average number of psychiatric diagnoses (total number determined by self-report and suggested by chart review) per individual did not differ between the sexes (M 1.06 ± 0.73, F 1.10 ± 0.57; p = 0.8687, t = 0.1670).

FIGURE 3

FIGURE 3

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Therapeutic and Health Care Utilization in the Study Cohort Subset With Likely/Possible ORS

Figure 4 summarizes the most common treatments used and health care specialties consulted by patients with likely or possible ORS. Approximately two thirds of ORS patients introduced dietary restrictions and used various supplements to address their perceived odors (Fig. 4A). The majority (77.5%) of individuals in this cohort consulted at least one other specialty in addition to genetics (Fig. 4B), with 43% consulting three or more specialties. On average, there was no significant difference between the number of specialties consulted between the sexes (F 2.36 ± 1.19, M 2.53 ± 1.06; p = 0.6446, t = 0.4650). The most frequently consulted specialties (Fig. 4C), other than genetics, were psychiatry (38.7%), gastroenterology and naturopathy (29% each), dermatology (22.6%), and dentistry (19.4%).

FIGURE 4

FIGURE 4

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Comparison of the ORS Cohort Subset to the Non-ORS Subset and to Literature Cohorts

Two individuals in the study cohort were diagnosed with TMAU and removed from comparative analyses. Seven individuals received other diagnoses and were deemed unlikely to be affected with ORS. Comparison of the cohort subsets with (n = 45) and without (n = 7) ORS (data not shown) did not identify any significant differences between the groups for age at symptom onset, age when seen for genetic assessment, number who self-detected their odor, or the number of psychiatric diagnoses. For the non-ORS cohort (data available for 5/7), three (60%) consulted one other specialty other than genetics (dermatology in two cases and dentistry in one case), whereas the other two (40%) were only seen by genetics. There tended to be more individuals in the ORS subset with clinical findings suggestive of an undiagnosed or unreported psychiatric disorder compared with the non-ORS subset (73.3% vs. 57.1%; p = 0.3890, t = 0.8690; Fig. 3A). A significantly larger proportion of the ORS subset tried supplements as a therapeutic approach compared with the non-ORS subset (68.9% vs. 28.6%; p < 0.05). The odor descriptors differed between the ORS and non-ORS subsets (Fig. 2B), with the non-ORS group skewing toward food-related descriptions (71.4%; eggs, meat, coffee, fruit), followed by “fishy” (42.9%), “rotting” (42.9%), and “bad/pungent” (28.6%). In comparison, the ORS group tended to use more refuse-related terminology, with “fecal/sewage” (44.4%) being the most common descriptor, followed by “fishy” (35.6%) and “garbage” (31.1%). There was no significant difference between the two groups for the number of odor descriptors, locations, or triggers.

Table 1 shows the comparison of our study cohort to previous literature reports. In our study, a preponderance of females was identified as having ORS (62.2%), whereas, across the literature, there is a 3:2 bias for males. The average age of symptom onset in our cohort was 28 years, comparable to the average of 22.09 years across all reported cases and cohorts to date (including ours). The odor descriptors of “stool/fecal” and “garbage” are commonly used terms throughout the literature, and psychiatric comorbidities, especially mood and anxiety disorders, are consistently reported as frequent within the ORS patient population.

TABLE 1

TABLE 1

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DISCUSSION

This is the first study of a large and ethnically diverse patient cohort who meets the definition of ORS presenting within a genetic patient population. The presentation of this diverse cohort of patients to a genetics clinic and the number of specialty consultations sought before genetics assessment suggest that patients with ORS are driven to attain systemic diagnoses for their perceived body odor. The majority of patients implemented dietary restrictions and used various supplements to treat an as-yet undiagnosed systemic cause for their perceived malodor.

To our knowledge, there has not been another study showing that a major ascertainment point for ORS patients is the genetics clinic. Our findings speak to the need for recognition of this disorder by geneticists and the physicians who refer them for genetics assessment, as they are in a unique position to recognize the possibility of this diagnosis and refer to psychiatry. Although ORS falls within the realm of psychiatric diagnoses, it is rarely ascertained in the psychiatric population (GZ, personal communication); this is evident in the paucity of ORS-related literature to date. Within our cohort, other than genetics, the most common specialty consultation was psychiatry, yet only 1 of our 45 likely/possible ORS patients received a diagnosis of ORS before presenting to the genetics clinic. This striking discrepancy in diagnostic pick-up suggests a lack of awareness of this disorder among psychiatric specialists.

Although the categorization of ORS itself is currently undecided, resulting in its exclusion from the DSM-5, the high frequency of comorbid anxiety, mood and delusional disorders seen in our study and others (see Table 1 for examples) supports a strong need for psychiatric assessment and management, even in the absence of awareness of ORS as a diagnosis. Despite this, the majority of individuals (61.3%) in our study did not seek or were not referred for psychiatric assessment. Greenberg et al. (2018) also found that most individuals (86%) with ORS in their study cohort did not seek mental health services (Greenberg et al., 2018). The authors identified multiple barriers to treatment among individuals with ORS, including financial obstacles, stigmatization, and treatment perception. Even when psychiatric care is sought, it is often delayed, with an average 14-year delay from symptom onset to seeking psychiatric care having been reported (Prazeres et al., 2010).

Although comorbid anxiety was common in our study cohort, it is difficult to ascertain the temporality of which originated first, ORS or anxiety. A recent article suggests that ORS may result from having social anxiety (Tsuruta et al., 2017). In support of this, ORS symptoms have been shown to respond to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy, the typical first-line treatments used for social anxiety (for example, Arasalingam et al., 2011; Cruzado et al., 2012; Gkini et al., 2017; Lim and Wan, 2015; Teraishi et al., 2012; Zantvoord et al., 2016). There are also several studies that report improvement with a combination of an SSRI and an antipsychotic (Cruzado et al., 2012; Michael et al., 2014), or improvement with an antipsychotic alone (Albers et al., 2018; Yeh et al., 2009), which supports the delusional component of ORS.

In our study cohort, ORS patients reported multiple odor types, sources, and triggers. Importantly, the most common location of odors described across the ORS cohort was general body, in stark contrast to TMAU, where the distinct odor emanates from sweat, breath, and/or urine. The most common adjectives used by individuals with ORS to describe their perceived odors were fecal or sewage, which is consistent with the literature to date (Table 1; Begum and McKenna, 2011; Greenberg et al., 2016; Phillips and Menard, 2011).The “fecal/sewage” description, and the use of multiple adjectives, also effectively differentiates ORS from TMAU, which is characterized by a distinct fermented or rotten fish odor. Taken together, along with adult age of onset in ORS compared with congenital or childhood onset in TMAU, the reported odor location and description in ORS constitute key differentiating characteristics between ORS and TMAU. These criteria can be applied by physicians to counsel patients with possible ORS who are seeking referral for genetic assessment for TMAU, thus avoiding unnecessary utilization of health care resources, while supporting the more appropriate referral of patients to psychiatry. Interestingly, similar to TMAU, the most common odor triggers in the ORS study cohort were identified as food items. Anecdotally (J. S., personal communication), this may be due to hypotheses and treatment approaches discovered by patients on the Internet, resulting in patients adjusting their perceived symptom triggers accordingly.

The present study was limited by the retrospective nature of the data analyzed, although this was necessitated by the recognition of the ORS patient population in the genetics clinic over time. Future studies with in-depth psychiatric phenotyping will be essential to further refine the diagnostic criteria for ORS, and define the temporality between ORS and the commonly seen psychiatric comorbidities. This characterization will assist in the development of more targeted therapeutic strategies.

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CONCLUSIONS

ORS is a typically adult-onset disorder that is composed of a heterogeneous patient population who actively seek an organic etiology for their perceived general body malodor. In this study, we present the genetics clinic as an unexpected and major ascertainment point for these individuals as they seek an organic diagnosis, such as TMAU, to explain their perceived odors.

Our results support that ORS is pan-ethnic, and that it can be differentiated from non-ORS and TMAU cohorts on the basis of the odor descriptions and their locations of origin, as well as age of onset. ORS is also frequently associated with additional psychiatric diagnoses.

The results of our study and others demonstrate a lack of awareness and recognition of ORS, resulting in a low diagnostic rate, most notably among psychiatric specialists, attesting to the need for improved education and further studies regarding this condition to improve management, reduce stigma for patients, and ultimately save in health care resources.

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ACKNOWLEDGMENTS

The authors thank Hanna Faghfoury and Chantal Morel, medical geneticists, as well as Jennifer Semotok and Jillian Murphy, genetic counselors, at the University Health Network (Toronto, Ontario, Canada) for their involvement in the clinical assessments of the patients included in the study cohort.

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DISCLOSURE

The authors declare no conflict of interest.

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    Keywords:

    Olfactory reference syndrome; trimethylaminuria; obsessive-compulsive disorder; jikoshu-kyofu; taijin kyofusho

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