| |

Received: 2 December 2019    Revised: 17 February 2020    Accepted: 18 March 2020

DOI: 10.1111/nmo.13850

CLINICAL REVIEW

Diagnosis and management of globus sensation: A clinical

challenge

Frank Zerbib1  | Nathalie Rommel2  | John Pandolfino3 | C. Prakash Gyawali4

1
Department of Gastroenterology, Bordeaux
University Hospital, Université de Bordeaux,
Bordeaux, France
2
Department of Gastroenterology,
Neurogastroenterology & Motility, Catholic
University of Leuven, Leuven, Belgium
3
Division of Gastroenterology, Department
of Medicine, Northwestern University,
Chicago, IL, USA
4
Division of Gastroenterology, Washington
University School of Medicine, St. Louis,
MO, USA
Correspondence
C. Prakash Gyawali, Division of
Gastroenterology, Washington University
School of Medicine, 660 South Euclid Ave.,
Campus Box 8124, Saint Louis, MO 63110,
USA.
Email: cprakash@dom.wustl.edu
Abstract
Globus is a non-painful sensation of a tightness or a lump/foreign body in the throat
that is not associated with dysphagia and may actually improve during meals. While
several otorhinolaryngologic, thyroid, and esophageal disorders have been linked
to globus, cause-and-effect relationships are difficult to establish. Consequently,
though part of the evaluation, objective otorhinolaryngologic and esophageal testing
is often negative. The presence of alarm symptoms, particularly pain, weight loss,
dysphagia, or odynophagia is indications for objective testing. A diagnosis of idio-
pathic globus requires exclusion of pharyngeal, laryngeal, and esophageal disorders
with laryngoscopy, endoscopy, high-resolution manometry, barium radiography, and/
or ambulatory reflux monitoring. A trial of acid-suppressive therapy may be reason-
able in the absence of alarm symptoms, especially if concurrent reflux symptoms
are identified. Ablation of heterotopic gastric mucosa in the proximal esophagus
has been reported to improve globus symptoms. Beyond these specific approaches,
further management of idiopathic globus consists of reassurance, neuromodulators,
and complementary approaches. Globus has a benign course with no long-term con-
sequences, and the overall prognosis is good as the magnitude of symptoms may
decline over time.

KEYWORDS

ambulatory reflux monitoring, globus, high-resolution manometry, neuromodulators,

videofluoroscopy

1 |  I NTRO D U C TI O N
Globus sensation is defined as a persistent or intermittent non-pain-
ful sensation of a lump or foreign body in the throat localized to the
1
midline between the thyroid cartilage and sternal notch, although
some patients may find the symptom difficult to localize or may
localize it unilaterally rather than in the midline or bilaterally. 2 The
symptom may be reported as a tightness, itching, or tickling sen-
sation. Patients may also describe a sense of retained particulate
matter, mucus accumulation, or a restrictive or choking sensation.
However, globus does not impair passage of food and hence is dis-
tinct from obstructive dysphagia. Typically, globus symptoms are
more frequent between meals and may remain unchanged or even
improve during swallowing, which can be a distinguishing feature
from true dysphagia. The presence of true dysphagia or odynopha-
gia, pain or weight loss is not compatible with idiopathic globus and
may indicate the need for investigation for an alternate mechanism
for symptoms.1
While globus is common, prevalence varies widely depending
on the definition utilized. In one study, only 51% of 216 patients

All authors contributed equally to the manuscript.

Neurogastroenterology & Motility. 2020;00:e13850. wileyonlinelibrary.com/journal/nmo |

© 2020 John Wiley & Sons Ltd     1 of 8
https://doi.org/10.1111/nmo.13850
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2 of 8       ZERBIB et al.
localized globus to the high neck; of the remainder, 35% localized
the symptom between the thyroid notch and sternum, and 15% sub-
sternally.3 Prevalence rates as low as 0.1% and as high as 46% have
been reported, with females presenting for evaluation more often
than males.4-6 In a questionnaire survey with 3000 respondents in
China, the lifetime prevalence was 21.5%, with peak age of onset at
35-54 years, and without a gender preference.7 A population survey
of 6300 individuals in the United States, UK, and Canada reports
a prevalence of 8.1%, with similar prevalence in each of the three
regions.8 Globus may account for as many as 4% of new referrals
to ENT clinics.9,10 Anxiety, depression, and sleep disorders were re-
ported more often in patients with globus than those without the
symptom.7 Consequently, patients with globus present to ear-nose-
throat (ENT), gastroenterology, and psychiatry clinics.
2 |  E TI O LO G Y O F G LO B U S
Idiopathic globus is diagnosed when the clinical history is support-
ive and after alternate medical conditions have been excluded using
prudent and specific investigation, including laryngoscopic evalua-
tion, endoscopy with biopsy, high-resolution manometry (HRM), and
1
in some instances, ambulatory reflux monitoring. Although as many
as 90% of patients presenting to ENT clinics are reported to have ab-
normal bolus propulsion on videofluoroscopic examination, these do
3,11
not necessarily correlate to the location or nature of the symptom.
Abnormal endoscopy (22%), abnormal pH testing (20%), motor ab-
normalities on HRM (63%), and abnormal barium swallow (24%) were
reported in 172 patients presenting to ENT clinics for evaluation.12
However, there were no differences in videofluoroscopy between
healthy adults and patients with globus in terms of in hyoid bone
displacement, pharyngeal transit time, pharyngeal constriction ratio,
or maximum opening of the esophageal entrance, suggesting that
no pharyngeal motor dysfunction is present or that findings on test-
13
ing may not necessarily be linked to globus as a symptom. Benign
findings noted on videofluoroscopy in a prospective study of 218
globus patients included reflux changes (2%), candida esophagitis
(2%), and cricopharyngeal dysfunction (9%); the likelihood of finding
upper aerodigestive tract cancers was <1%.14 Other studies have re-
ported no diagnostic benefit in performing videofluoroscopy, barium
esophagram, and thyroid ultrasound in patients with idiopathic glo-
15,16
bus and negative ENT evaluation. However, these investigative
tests may have exclusionary value, and it is therefore important to
understand the spectrum of abnormalities that could be identified
on investigation.
In recent years, heterotopic gastric mucosa (inlet patch) in the
cervical esophagus has received attention as a potential mechanism
for globus, based on symptom improvement following ablation in
small cases series reports involving 10-11 patients.17,18
Thyroid disease and thyroid surgery have both been reported as
etiologic factors for globus. In a cohort of 616 patients with various
thyroid disorders (cancer, benign tumors, and diffuse goiters), almost
30% had an abnormal foreign body sensation in the throat (FBST)
score preoperatively. Following surgery, almost 80% had an abnor-
mal score at 1 month, which decreased to approximately 50% at
12 months, suggesting that thyroid surgery may participate in globus
sensation.19 Despite the fact that several thyroid abnormalities have
been linked to globus, the likelihood of globus was higher in patients
with normal thyroid volume on ultrasound compared to patients
with abnormal volume in a 2-year prospective study of 56 patients. 20
Esophageal motor abnormalities, particularly pertaining to the
upper esophageal sphincter (UES) have been described in globus,
but it remains unclear if the findings are causative of the symptom,
or a consequence of concurrent anxiety. A reactive, hyperdynamic
UES with respiration, 21 high UES resting pressures, 22 and elevated
UES postswallow residual pressures23,24 have been reported. There
are limited data demonstrating that a lowering of UES pressure
with neuromodulator therapy (paroxetine and amitriptyline) can be
associated with improvement in globus symptoms. 25 An increased
basal UES pressure on HRM should be interpreted with caution,
as this metric is highly labile and may be augmented by discomfort
and emotional distress, including that induced by the HRM study. 26
Moreover, an increased UES pressure may be a protective reflex sec-
ondary to abnormal gastro-esophageal reflux or esophageal stasis to
prevent aspiration. 27
It is assumed, although not clearly demonstrated, that impaired
bolus transit and esophageal distension may generate globus sensa-
tion. Many studies report cases of achalasia and esophageal spasm
in patients presenting with globus as primary symptom, and UES
pressures can be elevated from a reflex mechanism with esoph-
ageal pressurization. 28,29 As an example, a study reported 27% of
patients with achalasia in patients with globus, but other symptoms
more typical of achalasia like dysphagia and regurgitation were also
found to be present in most patients after careful interview.30 By
contrast, minor motor disorders, such as ineffective esophageal mo-
tility, cannot be reliably linked to the globus sensation, as controlled
studies have shown similar prevalence in patients and controls.31
Consequently, manometry has both rule-in and rule-out value in di-
agnosis or exclusion of major motor disorders.
In a small cross-sectional study of 17 globus patients, 10 had
obstructive sleep apnea, and globus improved with management of
sleep apnea using an airway appliance such as continuous positive
airway pressure (CPAP).32 Another study reported development of
globus following radiofrequency ablation of the tongue base as a
form of management of obstructive sleep apnea.33
While neuromodulators and psychotropic medications are often
used in the management of idiopathic globus, some psychotropic med-
ications can cause globus. In a small study of 16 healthy volunteers
who were administered 20 mg of intravenous citalopram, five reported
globus and had higher UES postswallow mean and maximum pressure
values.34 Anticholinergic medications have also been linked to globus,
presumably by drying out salivary and oropharyngeal secretions.35
Patients with muscle tension dysphonia, a functional laryngeal disor-
der, have a higher prevalence of globus compared to those with organic
dysphonia.36 Globus has also been reported to occur concurrently with
burning mouth syndrome in one small case series of 22 patients.37
ZERBIB et al. |
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The role of GERD as a potential cause of globus has been sug-

gested by several studies.2,5,11,12,31,38 The hypotheses underlying
symptom generation consist of the following: (a) regurgitation lead-
ing to pharyngeal irritation; (b) reflex contraction of the UES, and (c)
altered localization of esophageal sensation to the neck. Globus has
been reported in up to 28% of patients with typical reflux symptoms,
that is, heartburn and acid regurgitation. The presence of pathological
gastro-esophageal reflux can be demonstrated or suspected at en-
doscopy by the presence of significant peptic esophagitis and hiatal
hernia, found in 5%-38% and 6%-52% of patients with globus, respec-
tively.2 Reports in the literature utilizing pH or pH-impedance studies
have shown conflicting results and could not definitely establish that
patients with globus have higher acid exposure time, and elevated
numbers of acid or non-acid reflux episodes.2 Moreover, it is virtu-
ally impossible to establish a temporal relationship between the oc-
currence of a reflux event and globus sensation, which does not have
a discrete onset unlike other esophageal or ENT symptoms. Finally,
though response to antireflux therapy could support a relationship
between underlying gastro-esophageal reflux and globus, the poten-
tial high placebo response in this clinical setting and the absence of
randomized controlled trials makes it virtually impossible to reliably
establish a link between GERD and globus.
When no etiologies are identified with appropriate investigation,
idiopathic or functional globus is diagnosed. The current dominant
concept regarding the symptom generation in functional globus is
visceral hypersensitivity, which may overlap or coexist with other
potential mechanisms such as gastro-esophageal reflux and esoph-
F I G U R E 1   Esophageal sensory thresholds to balloon distension
ageal or UES motor dysfunction. Indeed, it has been shown that
showing cumulative response rates for (A) first perception and
patients with globus not only have lower sensory thresholds to (B) pain threshold, to balloon distension. When compared with
esophageal distention (Figure 1), but also report aberrant pain refer- controls, note the left shift in perception (P = .03) and pain
ral to a site at or above the suprasternal notch compared to controls thresholds (P = .001) of globus patients. Reproduced from Chen
(Figure 2), thus suggesting a central rather than a peripherally me- et al,39 with permission

diated phenomenon.39 While no hard evidence exists, it is plausible

that globus can exist concurrently with other esophageal functional
disorders, including functional heartburn, functional chest pain, and
reflux hypersensitivity.1
There is a strong overlap between idiopathic globus and affec-
tive disorders. In a prospective evaluation of 104 patients with glo-
bus, as many as 35% had anxiety disorder, and 13% had depression;
40
18% had borderline anxiety, while 28% had borderline depression.
Anxiety and hypochondriasis scores are higher in globus patients
41
compared to those without this symptom, and in urban residents
compared to rural residents.42 Both anxiety and depression appear
to be more prevalent in females.40 Other behavioral disorders such
as supragastric belching have also been reported at higher frequen-
43
cies in globus patients compared to controls.
3 | D I AG N OS I S O F G LO B U S
The diagnosis of globus starts with taking a careful history, particu-
larly to distinguish globus from oropharyngeal dysphagia, esopha-
geal dysphagia, and upper airway symptoms (Figure  3). While the
presence of concomitant typical reflux symptoms could raise the
possibility of reflux disease, standard questionnaires such as the
GERDQ have poor sensitivity (33%) to diagnose GERD in globus pa-
tients compared to ambulatory reflux monitoring, despite excellent
specificity (89%), and good prediction of PPI response (sensitivity
69%, specificity 70%, positive predictive value 99%).11 The Glasgow
Edinburgh Throat Scale (GETS) is a 10-item questionnaire with three
subscales relating to globus and other throat symptoms.44 Because
of high specificity for globus, this scale has value in objective char-
acterization of globus. The FBST score uses patient responses to 11
questions to generate a total score between 0 (no sensation per-
ceived) and 8.2 (maximum perception of sensation in the neck) to
quantify patient reports of foreign body sensation and has been
used occasionally in the literature to assess change in globus symp-
toms after intervention.19
The diagnostic work-up of a patient presenting with globus has
the objective of differentiating secondary globus from idiopathic
or functional globus.1 Concurrent pain, weight loss, odynophagia,
or dysphagia should raise the possibility of structural lesion war-
ranting investigation, particularly endoscopic and laryngoscopic
 |
4 of 8       ZERBIB et al.
assessment.44,45 While invasive testing may uncover abnormali-
ties frequently on ENT examination, endoscopy, videofluoroscopy,
12
esophageal manometry, and reflux monitoring, a cause-and-effect
relationship is difficult to establish between abnormalities and glo-
bus sensation.
An ENT examination, if needed associated with laryngoscopy
and thyroid ultrasonography (when thyroid abnormalities are sus-
46
pected), should be the first step to rule out any structural lesion of
the oropharynx and larynx. Once oropharyngeal structural lesions
have been ruled out, esophageal disorders should be investigated
using upper gastrointestinal endoscopy. Esophageal structural le-
sions are rare in patients presenting with globus as a main or primary
symptom. Transnasal laryngoscopy and esophagoscopy have exclu-
sionary value in ruling out significant lesions in the upper aerodiges-
tive tract in the evaluation of globus.47
The next step is to consider GERD as a potential mechanism of the
globus sensation.2,5,11,12,31,38 An empiric PPI trial is recommended in
the absence of alarm symptoms to determine whether globus is re-
1,2
sponsive to acid suppression. Despite the absence of controlled
supporting data, and although response to PPI therapy cannot be con-
sidered as unequivocal evidence for GERD, a 4 to 8-week PPI empiric
therapy is safe and may improve symptoms in up to 70% of patients,38
especially when typical reflux symptoms coexist.
Upper endoscopy is indicated in the presence of alarm symp-
toms or with PPI non-response (Figure 3). The presence of a gastric
inlet patch in the cervical esophagus has been linked to the globus
F I G U R E 2   Patterns of viscerosomatic
referral of pain in response to mid-
esophageal stimulation by (A) balloon
distension and (B) electrical stimulation in
healthy controls (left) and in patients with
globus (right). Reproduced from Chen et
al,39 with permission
sensation and should be considered for treatment. Indeed, up to
23% of patients with gastric inlet patch complain of globus symp-
tom2 and a controlled study reported a significant and sustained
symptomatic improvement after argon plasma coagulation of the
heterotopic mucosa.17 Efficacy of radiofrequency ablation in improv-
ing globus symptoms has been reported in a small uncontrolled se-
ries.18 Adenocarcinoma, Barrett's esophagus, and Helicobacter pylori
are reported as rare consequences of inlet patches.48-50 Therefore,
if present, biopsy and ablation of the gastric inlet patch can be
considered.1,2
Whether ambulatory reflux monitoring should be performed can
be debated but if no other cause can be identified, it may be useful to
perform ambulatory pH (or pH-impedance) monitoring off therapy
to document abnormal baseline reflux metrics which could justify
optimization of GERD treatment.1,2 On the other hand, negative pro-
longed wireless pH monitoring performed at index endoscopy could
provide robust exclusion of abnormal acid exposure and avoid un-
necessary PPI therapy,51,52 while a positive pH study would establish
GERD and predict PPI response.53 In globus patients, as with other
“supra-esophageal” symptoms suspected to be related to esopha-
go-pharyngeal regurgitation, the assessment of proximal esophageal
or pharyngeal reflux has been proposed, with either dual esophageal
pH, pharyngeal pH or pH-impedance probes. However, considering
that neither methodology nor interpretation of these tests are stan-
dardized, proximal reflux recording is not considered reliable and is
not recommended.54
ZERBIB et al.
F I G U R E 3   Proposed algorithm for the diagnosis of globus. *After a careful clinical evaluation and inspection of the oropharynx via
direct laryngoscopy, evaluation can proceed in a stepwise fashion. The order of the tests and trials may be modified by clinical suspicion.
Functional globus should be diagnosed after the appropriate ROME IV exclusion criteria have been applied
a
TA B L E 1   ROME IV diagnostic criteria for globus sensation
Must include all of the following:
1. Persistent or intermittent, non-painful, sensation of a lump or
foreign body in the throat with no structural lesion identified on
physical examination, laryngoscopy, or endoscopy.
a. Occurrence of the sensation between meals
b. Absence of dysphagia or odynophagia
c. Absence of a gastric inlet patch in the proximal esophagus
2. Absence of evidence that gastro-esophageal reflux or
eosinophilic esophagitis is the cause of the symptom
3. Absence of major esophageal motor disordersb 
a
Criteria fulfilled for the last 3 mo with symptom onset at least 6 mo
prior to diagnosis with a frequency of at least once a week.
b
Achalasia/EGJ outflow obstruction, diffuse esophageal spasm,
Jackhammer esophagus, absent peristalsis.
Finally, high-resolution manometry should be performed to rule
out major esophageal motor disorders as defined by the Chicago
Classification, that is, achalasia, distal esophageal spasm, hyper-
contractile esophagus, and absent peristalsis. 55 It remains unclear
at this stage whether minor esophageal disorders, although often
present, can be considered as a potential explanation for globus
sensation.
If no secondary cause of globus can be demonstrated, the final
diagnosis should be functional globus or globus sensation accord-
ing to the Rome IV definition (Table 1), where sensory dysfunction
1
and visceral hypersensitivity probably play a major role. A cursory
psychological assessment should be done in all instances, and more
|
      5 of 8
detailed psychiatric evaluation when indicated, similar to that rec-
ommended for other functional gastrointestinal disorders. Indeed,
as anxiety and depression of various degrees have been reported
in globus patients,30,31,56 it seems reasonable to screen for these
comorbidities using simple questions and/or short screening in-
struments and if necessary, to refer patients to a behavioral health
specialist for further assessment. Moreover, the role of life stress
events has been demonstrated by several studies 57,58 and should be
considered in subsequent patient management.
4 | M A N AG E M E NT O F G LO B U S
When structural laryngeal and esophageal disorders are identified,
treatment of these disorders can proceed, even though evidence for
a cause-and-effect relationship between structural disorders and
globus is scant. Radiofrequency ablation of large inlet patches meas-
uring >2 cm has been reported to improve reporting of globus on
10 cm visual analog scales, from 8 at baseline to 1 on follow-up of a
mean of 2 years after ablation.18 In a randomized controlled study,
endoscopic argon plasma coagulation of inlet patches improved glo-
bus in 80% compared to 0% relief with sham endoscopy, with benefit
lasting as long as 17 months in 76% of treated patients.17 Ablation of
heterotopic gastric mucosa (inlet patch) using argon plasma coagula-
tion or radiofrequency ablation may be considered if no other struc-
tural abnormalities are identified17,59,60 and especially if PPI trials or
neuromodulators have not provided a response. Similarly, esopha-
geal bolus retention seen in disorders associated with esophageal
 |
6 of 8       ZERBIB et al.
outflow obstruction can induce perceptive symptoms from reflexive
28
UES contraction and hypersensitivity, and treatment of these dis-
orders is recommended when identified.
After ruling out structural lesions, empiric PPI therapy can be
considered because of the pragmatic, non-invasive nature of such
1
trials. Symptom response is marginal and mostly when concur-
rent typical reflux symptoms are identified. The finding of abnor-
mal esophageal acid burden on ambulatory reflux monitoring can
guide need for long-term acid suppression. If no symptom benefit
is noted, especially in the absence of abnormal pH-metry, PPIs can
be weaned off.
After exclusion of structural, mucosal, and motor disorders, the
remainder of management consists of reassurance, use of neuro-
modulators, and complementary approaches. As many as half of
globus patients report symptom improvement or resolution with
reassurance alone without specific management, compared to treat-
ment with antidepressants.61,62 Formal relaxation techniques such as
hypnotherapy have been reported to improve globus symptoms. In a
small open label trial of 10 patients who agreed to enroll in a 7-ses-
sion hypnotherapy protocol, 90% reported symptom improvement,
despite no changes in UES function on manometry.63 Exercises di-
rected at improving pharyngolaryngeal tension, typically adminis-
tered by speech pathologists, have also been reported to provide
symptom benefit in uncontrolled reports.64 The value of behavioral
therapy and exercises lie in the fact that these are not associated
with risks or side effects that medications often entail but require
buy-in from the patient.
In addition to behavioral approaches, certain non-pharmacolog-
ical supplements have been utilized in managing globus symptoms.
Rikkunshito, a Japanese herbal medication, has been reported to im-
prove globus symptoms, when used alone or combined with PPIs in
patients with concurrent reflux disease.65,66 In a single case report,
acupuncture is reported to benefit globus symptoms.67
Neuromodulators are often utilized in the management of idio-
pathic globus, and this can be considered if alternative approaches
described above do not provide benefit, especially in the setting
where quality of life is significantly impacted. In a randomized con-
trolled trial comparing acid suppression with pantoprazole 40 mg
once daily versus 25 mg of amitriptyline daily in globus patients, am-
itriptyline (75% response) was significantly superior to pantoprazole
(36% response).68 Selective serotonin reuptake inhibitors (SSRI) such
as paroxetine have been utilized with success in the management of
globus. 25 The benefit may extend beyond management of visceral
hypersensitivity to treatment of concurrent anxiety, but use may be
associated with higher withdrawal rates due to symptom relapse.
5 |  PRO G N OS I S
Globus has a benign course without long-term sequelae. A prospec-
tive study of 76 globus patients demonstrated no development of
ENT cancers over 3 years of follow-up.15 However, globus can affect
quality of life, with as many as three quarters of patients continuing
to be symptomatic at 3 years after diagnosis45 and half at 7  years
after diagnosis.69 In limited case series, use of neuromodulators68
and ablation of inlet patch18 has been demonstrated to improve
symptoms and quality of life in globus patients. Reassurance and
limited diagnostic testing to exclude other abnormalities by itself
can reduce the magnitude of globus symptoms over time, as dem-
onstrated in a questionnaire-based prospective study of 30 globus
patients.70
6 | CO N C LU S I O N S
Globus is a chronic functional disorder of the upper aerodigestive
system. Investigation is often unremarkable, but recommended in
the presence of alarm symptoms, or for making a definitive diagnosis
of idiopathic globus. Visceral hypersensitivity and hypervigilance are
likely underlying pathophysiologic mechanisms, and coexisting anxi-
ety is often identified. When identified, secondary etiologic factors
are targeted for specific management. Treatment consists of reas-
surance, neuromodulators, and complementary therapy.
C O N FL I C T O F I N T E R E S T S
No conflicts of interest exist.
D I S C LO S U R E S
FZ: Reckitt Benckiser; NR: None; JEP: Medtronic, Diversatek, Torax,
Ironwood, Takeda, and Astra Zeneca (consulting); Impleo (research
funding); Crospon (stock options); CPG: Medtronic, Diversatek
(teaching and consulting), Ironwood, Iso-thrive (consulting).
ORCID
Frank Zerbib  https://orcid.org/0000-0002-6802-2121
Nathalie Rommel  https://orcid.org/0000-0001-5675-7334
C. Prakash Gyawali  https://orcid.org/0000-0002-3388-0660
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How to cite this article: Zerbib F, Rommel N, Pandolfino J,
Gyawali CP. Diagnosis and management of globus sensation:
A clinical challenge. Neurogastroenterol Motil.
2020;00:e13850. https://doi.org/10.1111/nmo.13850