INTRODUCTION — Globus sensation is a functional esophageal disorder characterized by a sensation of a lump or foreign body in the throat. Globus sensation has also been referred to as globus pharyngeus and the misnomer "globus hystericus." This topic will review the epidemiology, etiology, diagnosis, and management of patients with globus sensation. The evaluation of oropharyngeal and esophageal dysphagia are discussed in detail, separately. (See "Approach to the evaluation of dysphagia in adults" and "Oropharyngeal dysphagia: Clinical features, diagnosis, and management".)

DEFINITION — Globus sensation is a functional esophageal disorder characterized by a sensation of a lump, retained food bolus, or tightness in the throat that is not due to an underlying structural lesion, gastroesophageal reflux disease, mucosal abnormality, or an esophageal motility disorder [1].

EPIDEMIOLOGY — A sensation of a lump or foreign body in the throat is common in the general population. In a cross-sectional survey of over 3000 participants, the lifetime prevalence of globus was 22 percent [2]. Globus sensation accounts for 4 percent of visits to otolaryngology clinics [3]. The symptom is equally prevalent in men and women among healthy individuals in the community, but women are more likely to seek evaluation [2]. In primary care, one study reported the prevalence amongst consulters to be 6.7 per 100,000 practice encounters [4].

ETIOLOGY AND PATHOGENESIS — The pathogenesis of globus sensation is unclear. Visceral hypersensitivity, abnormalities of the upper esophageal sphincter (UES), psychologic and psychiatric disorders, and reflux have all been implicated.

Visceral hypersensitivity — Hypersensitivity to balloon distention is a common feature in patients with globus sensation. In one study, nine patients with globus were found to be hypersensitive to balloon distention but not electrical stimulation of the esophagus as compared with healthy controls [5]. In addition, the majority of patients with globus and none of the healthy controls referred the sensation during balloon distention to the suprasternal notch, suggesting that patients with globus may have aberrant central processing of esophageal sensations.

Upper esophageal sphincter dysfunction — Studies using high resolution manometry have identified abnormal UES function as a potential a cause of globus sensation [6,7]. One report found that respiration-related changes in resting UES pressure were significantly amplified in patients with globus sensation compared with controls [6]. In another study, measurable UES residual pressure occurred more often in patients with globus compared with a control group (67 versus 10 percent) [7].

In a study utilizing a circumferential solid state transducer, a hypertensive UES was found much more frequently among patients who reported globus sensation than controls (28 versus 3 percent) [8].

Psychologic abnormalities — Patients with globus sensation score higher on self-reported measures of neuroticism, introversion, anxiety, and depression than controls [9,10]. Psychologic disturbances including anxiety and somatic concerns are more common in women with globus sensation [11-13]. However, so called "hysterical" personality traits do not appear to be more common in patients with globus sensation; thus, the term "globus hystericus" is a misnomer and should not be used [12,14]. Furthermore, despite these associations, not all patients with globus sensation have psychologic or psychiatric abnormalities. Acute stress has been implicated in precipitating episodes of globus sensation, possibly by affecting UES pressure. Although a controlled trial did not demonstrate differences in UES pressure between seven patients with globus sensation and 13 controls after provocation with predictable stressful stimuli, UES hyperresponsiveness to other stimuli or subjective intolerance to changes in UES pressure may account for symptoms of globus sensation [9].

Gastroesophageal reflux — Globus is an atypical manifestation of gastroesophageal reflux disease (GERD) in a subset of patients. It is hypothesized that globus may be related to UES contraction induced by acid exposure in the distal esophagus [15]. However, GERD does not have a major role in the pathogenesis of globus. While an association between globus sensation and GERD has been suggested in studies that have found that patients with globus were significantly more likely than controls to have abnormal pH studies, discordant data have also been reported [8,15-21]. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults" and "Esophageal multichannel intraluminal impedance testing".)

CLINICAL MANIFESTATIONS — Patients have a sense of a lump, a retained food bolus, or tightness in the throat. Globus sensation is not painful and is typically worse when swallowing saliva (dry swallow) and less noticeable when swallowing solids or liquids. In approximately 70 percent of patients, globus symptoms are intermittent [22].

DIAGNOSIS — Globus sensation is suspected in patients with a sensation of a lump or foreign body in the throat and the absence of symptoms of gastroesophageal reflux disease (GERD) symptoms (heartburn or regurgitation) or an esophageal motility disorder (dysphagia or atypical chest pain). A definitive diagnosis requires an evaluation to exclude other causes of similar symptoms including GERD and an esophageal motility disorder. The low yield of diagnostic evaluation in patients with globus sensation is the rationale for a stepwise diagnostic approach [22-26].

Diagnostic approach

●All patients with globus symptoms should initially undergo a history and physical examination that includes examination of the oropharynx and larynx.

●In patients with recurrent symptoms or persistent symptoms that fail to resolve with conservative management or those with alarm features (pain, lateralization of the symptoms, dysphagia, odynophagia, weight loss, a change in voice, presence of a neck or tonsillar mass, and unexplained cervical adenopathy), we pursue additional evaluation to rule out other causes and to establish a definitive diagnosis of globus sensation.

●A definitive diagnosis of globus sensation requires the fulfillment of all of the following criteria [1]:

•The persistent or intermittent, nonpainful sensation of a lump or foreign body in the throat with no structural lesion identified on physical examination, laryngoscopy or endoscopy.

•Occurrence of the sensation between meals.

•Absence of dysphagia or odynophagia.

•Absence of a gastric inlet patch in the proximal esophagus.

•Absence of evidence that gastroesophageal reflux or eosinophilic esophagitis as the cause of symptoms.

•Absence of major esophageal motor disorders (achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, jackhammer esophagus, absent peristalsis).

•Criteria fulfilled for the last three months with symptom onset at least six months before diagnosis.

History and physical examination — The clinical history should focus on the duration, intensity, and progression of symptoms, and their impact on quality of life. Patients should be evaluated for symptoms of reflux including heartburn and regurgitation. Risk factors for a malignancy including a history of radiation to the head and neck, smoking, and alcohol consumption should be sought. Alarm symptoms that are not associated with globus sensation include pain, lateralization of the symptoms, dysphagia, odynophagia, weight loss, and a change in voice [27]. Physical examination should include examination of the neck and oropharynx, which usually requires otolaryngological referral, and palpation of the thyroid gland. The presence of alarm symptoms, a neck/tonsillar mass or unexplained cervical adenopathy requires additional evaluation. (See 'Additional evaluation' below.)

Additional evaluation — In patients with recurrent or persistent symptoms despite conservative management or those with alarm features, we pursue additional evaluation. Alarm features include pain, lateralization of the symptoms, dysphagia, odynophagia, weight loss, change in voice, presence of a neck or tonsillar mass, and unexplained cervical adenopathy.

Nasoendoscopy — Otolaryngologic examination with transnasal fiberoptic laryngoscopy (FOL) or, if available, transnasal flexible laryngoesophagoscopy (TNE) allows for a detailed examination of the oropharynx, hypopharynx, larynx, and proximal esophagus to rule out a structural lesion.

Videofluoroscopy — Videofluoroscopy helps identify functional and structural abnormalities of the pharynx. Videofluoroscopy serves to detect oropharyngeal dysfunction and to assess the degree of dysfunction and severity of aspiration.

Imaging — A barium swallow with a solid bolus (eg, a barium tablet) serves to exclude a mechanical problem and to look for an obvious, underlying motility disorder [24,28]. In individuals suspected to have thyroid enlargement or nodules on physical examination or symptoms of thyroid dysfunction, we perform a thyroid ultrasound [29]. We reserve the use of neck computed tomography (CT)/magnetic resonance imaging (MRI) for patients with cervical adenopathy or a substernal goiter [28]. (See "Clinical presentation and evaluation of goiter in adults".)

Esophageal manometry — Manometry provides quantitative evaluation of the pressures and relative timing involved in the pharyngeal contraction and deglutitive upper esophageal sphincter (UES) relaxation and an assessment of esophageal motility to rule out an esophageal motility disorder.

Esophageal pH and impedance — We assess esophageal pH with impedance in patients who fail to respond to a trial of acid suppression therapy. Esophageal pH with impedance serves to detect if there is an increase in acid or non-acid reflux and if it correlates with globus sensation [19,30].

Upper endoscopy — Upper endoscopy serves to rule out a gastric inlet patch, eosinophilic esophagitis, or another mucosal process that can cause similar symptoms.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of globus sensation includes other causes of sensation of a lump or foreign body in the throat (table 1). The two most common causes include gastroesophageal reflux disease and an esophageal motility disorder. Globus sensation can be differentiated from these by esophageal manometry testing and esophageal impedance and pH testing [22]. (See 'Diagnostic approach' above.)

MANAGEMENT — The most effective treatment of globus sensation has not been defined. This is attributable to the lack of convincing evidence from randomized trials, possibly due to different pathophysiologic mechanisms involved in individual patients and the poor correlation of manometric findings with symptoms.

Initial management

Conservative therapy — Patients should be reassured that globus sensation is a benign disorder. In patients with coexisting psychologic or psychiatric conditions, psychiatric consultation may assist patients in coping with the sensation [22].

Acid suppression — In patients with persistent symptoms despite conservative management, we suggest a limited trial of acid suppression therapy with a proton pump inhibitor (PPI) (eg, omeprazole 20 mg twice daily) to treat undiagnosed gastroesophageal reflux disease (GERD) [31]. If symptoms do not start to improve within six to eight weeks of use, we discontinue PPI therapy. Approximately one-third of patients with symptoms suggestive of globus sensation experience partial relief with a PPI and have undiagnosed GERD [32].

Subsequent management — If initial management fails, additional evaluation should be performed to detect structural abnormalities, refractory GERD, and an esophageal motility disorder. (See 'Additional evaluation' above.)

Antidepressants — For patients with persistent symptoms that are not relieved by acid suppression, especially if there are concomitant psychiatric disorders (eg, panic disorder, somatization, major depression, and agoraphobia), we suggest the use of an antidepressant (eg, a low-dose tricyclic antidepressant such as imipramine 25 mg at bedtime). (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects".) In a small controlled trial in which 30 globus patients were assigned to treatment with 25 mg amitriptyline once daily and 40 mg pantoprazole once daily, after four weeks, a significantly higher percentage of patients in the amitriptyline group responded to treatment compared with the pantoprazole group (75 versus 36 percent) [33]. In patients with depression and globus sensation, the use of antidepressants have been associated with an improvement in globus symptoms, sleep quality, and mental health [34-36].

Other — Other therapies have been evaluated in patients with refractory symptoms, but evidence to support their use is limited [22,32,37,38].

●Gabapentin – A retrospective study evaluated the effectiveness of gabapentin in the treatment of 31 patients with globus. Of the 14 patients who had previously failed a trial of PPI therapy, eight had a partial or complete response to gabapentin (57 percent). Of the remaining 12 patients who responded partially to PPI therapy before their gabapentin trial, nine had additional improvement with gabapentin. Four of the five patients who never had PPI therapy improved on gabapentin.

●Relaxation therapy – In a case series, 10 women with globus who were unresponsive to reflux treatment and with normal esophageal/laryngeal imaging underwent a seven-session clinical protocol with hypnotically-assisted relaxation [39]. Following treatment, nine out of the 10 patients reported a reduction in globus symptomatology.

●Ablation of inlet patch – For patients with globus in the setting of a gastric inlet patch, endoscopic ablative therapy with argon plasma coagulation (APC) or radiofrequency ablation [40] may provide symptomatic improvement for some patients [41]. In a report of 31 patients with globus who had an inlet patch in the proximal esophagus, symptom scores by visual analog scale improved significantly after APC therapy at a median follow-up interval of 27 months. Overall, 23 of 31 patients (74 percent) indicated that APC therapy provided a benefit.

PROGNOSIS — Globus sensation usually has a benign course. In one prospective study of 80 patients with globus sensation, during a mean follow-up of 27 months, symptoms improved or resolved in 25 and 35 percent of patients, respectively [42].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Esophageal manometry and pH testing".)

SUMMARY AND RECOMMENDATIONS

●Globus sensation is a functional esophageal disorder characterized by a sensation of a lump, retained food bolus, or tightness in the throat that is not due to an underlying structural lesion, gastroesophageal reflux disease (GERD), or a histopathology-based esophageal motility disorder. (See 'Definition' above.)

●The pathogenesis of globus sensation is unclear, but visceral hypersensitivity, abnormalities of the upper esophageal sphincter (UES), psychologic and psychiatric disorders, and reflux have all been implicated. (See 'Etiology and pathogenesis' above.)

●Patients have a sense of a lump, a retained food bolus, or tightness in the throat. Globus sensation is not painful and is typically worse when swallowing saliva (dry swallow) and less noticeable when swallowing solids or liquids. In approximately 70 percent of patients, globus symptoms are intermittent. (See 'Clinical manifestations' above.)

●Globus sensation is suspected in patients with a sensation of a lump or foreign body in the throat and the absence of symptoms of GERD (heartburn or regurgitation) or an esophageal motility disorder (dysphagia or atypical chest pain). A definitive diagnosis requires an evaluation to exclude other causes of similar symptoms (table 1). (See 'Diagnosis' above and 'Differential diagnosis' above.)

●All patients with globus symptoms should initially undergo a history and physical examination that includes examination of the oropharynx and larynx. In patients with recurrent symptoms or persistent symptoms that fail to resolve with initial management or those with alarm features (pain, lateralization of the symptoms, dysphagia, odynophagia, weight loss, a change in voice, presence of a neck or tonsillar mass, and unexplained cervical adenopathy), we pursue additional evaluation to rule out other causes and to establish a definitive diagnosis of globus sensation starting with a barium swallow with a solid bolus. (See 'Additional evaluation' above.)

A definitive diagnosis of globus sensation requires the fulfillment of the following criteria:

•The persistent or intermittent, nonpainful sensation of a lump or foreign body in the throat with no structural lesion identified on physical examination, laryngoscopy or endoscopy

•Occurrence of the sensation between meals

•Absence of dysphagia or odynophagia

•Absence of a gastric inlet patch in the proximal esophagus

•Absence of evidence that gastroesophageal reflux or eosinophilic esophagitis as the cause of symptoms

•Absence of major esophageal motor disorders (achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, jackhammer esophagus, absent peristalsis)

•Criteria fulfilled for the last three months with symptom onset at least six months before diagnosis

●Initial management of globus sensation is conservative, and patients should be reassured that globus sensation is a benign disorder. In patients with coexisting psychologic or psychiatric conditions, psychiatric consultation may assist patients in coping with the sensation. If globus symptoms persist, we suggest empiric trials of acid suppression therapy (Grade 2C). We limit the use of pharmacologic therapy with tricyclic antidepressants (eg, low-dose imipramine) to patients with persistent symptoms that are not relieved by acid suppression. We reserve the use of gabapentin and relaxation therapy in patients with refractory symptoms. (See 'Management' above.)