What you need to know
Globus from laryngopharyngeal reflux (LPR) classically occurs when swallowing saliva and not when eating or drinking
First line treatments include lifestyle measures, proton pump inhibitors, and sodium alginate liquids
A cancer pathway referral should be considered if there are associated persisting symptoms including pain, swallowing difficulty, or change in voice
Laryngopharyngeal reflux (LPR) is a common condition accounting for approximately 10% of all “ear, nose and throat” (ENT) referrals.1 It is caused by gastric contents passing up through the oesophagus and upper oesophageal sphincter resulting in macroscopic and microscopic inflammatory changes to the upper aerodigestive mucosa.2 This most commonly leads to the sensation of a lump in the throat, termed globus pharyngeus (box 1), as well as chronic throat clearing, excessive mucus, vocal hoarseness, and cough.3 This article offers an overview of the assessment and management of LPR.
Globus is Latin for sphere
Globus pharyngeus is a descriptive term for the sensation of a lump in the throat and does not imply the diagnosis
Globus can be caused by a wide range of throat disorders, the most common being laryngopharyngeal reflux
Globus hystericus describes a sensation of a lump in the throat caused by stress. It used to be the preferred term for globus before organic causes such as LPR were found to be causative and should no longer be used
What you should cover
Is the sensation of the lump in the midline or lateralised in a fixed position? The sensation of a lump in the throat from LPR tends to be felt in the middle of the throat, around the larynx, although it can present with changing locations. Fixed lateralised symptoms are more concerning for a throat cancer. The likelihood of an isolated, unexplained sensation of a lump in the throat leading to a cancer diagnosis is low, however, with a positive predictive value of 1.5% in one multicentre review of 4715 urgent referrals from primary care to a specialist head and neck cancer service.4
Does the patient feel the lump when eating and drinking or only when swallowing saliva? Globus from LPR classically occurs only when swallowing saliva and not when eating or drinking. The sensation of a lump in a fixed position of the neck or throat causing difficulty swallowing food or fluid requires further evaluation. If this continues for over three weeks in those 40 years of age or over, an urgent suspected cancer referral to a specialist head and neck unit is recommended by regional referral guidelines.5
Are there any risk factors for throat cancer? Past or present tobacco use and alcohol consumption are risk factors.67 Be mindful that the increasing prevalence of head and neck cancer related to human papilloma virus (HPV) infection means that the possibility of a malignancy can no longer be excluded automatically in non-smokers who do not drink alcohol.
Are there any other symptoms? LPR commonly occurs with other symptoms of mucosal inflammation of the upper aerodigestive tract. These include excessive mucus, a bitter taste, a sore throat, the sensation of reflux, a chronic dry cough, and vocal hoarseness. LPR symptoms are often worse at night when the patient is supine and can wake them up with coughing fits, choking, and a sensation of throat tightness.
Are there any symptoms of gastroesophageal reflux? Around a third of patients with gastroesophageal reflux disease (GORD) have symptoms of LPR.8
Are there any lifestyle factors? Triggers may include fried and fatty food, citrus fruits, chocolate, tomato, mint, acidic dressings, caffeine, carbonated drinks, and alcohol.9 Stress, smoking, eating too fast, eating less than three hours before bedtime, and irregular meal times are also believed to play a role in LPR.
When should I consider a cancer pathway referral? The UK National Institute for Health and Care Excellence (NICE) guidelines recommend considering a suspected cancer pathway referral (for an appointment within 2 weeks) for laryngeal cancer in people aged 45 years and over with a persistent and unexplained hoarseness or an unexplained lump in the neck.10 Regional referral guidelines may set lower thresholds for referral than NICE. For instance, the pan-London suspected cancer referral guide recommends a cancer pathway referral in anyone with four weeks of persistent, particularly unilateral, discomfort in the throat or anyone 40 years of age or older with a three week history of dysphagia, odynophagia, otalgia, or persistent unexplained hoarseness.5
What are the patient’s concerns? Some patients with LPR have high levels of anxiety and may have concerns that their globus sensation is caused by a cancer.11 Explaining that the throat tends to interpret any sensory input as a lump, even if there is only minor irritation, can help to alleviate concern. People can also report variable tightening, pressure, or lump in the throat when anxious or as a part of an anxiety or mood disorder.
Initial telephone or video assessment is now common in primary care. We recommend a face-to-face examination if there are atypical features or those suggestive of serious disease.
In LPR, the neck should be non-tender with no palpable abnormality.
Examine the palate, tongue, and tonsils to look for a possible lesion. The posterior pharynx can seem erythematous or “cobblestoned” in those with LPR.
Record the patient’s weight to assess for unintended weight loss that may prompt an urgent referral.
What you should do
Making the diagnosis
In primary care, LPR can be diagnosed clinically based on history and examination and a trial of empirical treatment. The reflux symptom index (table 1) is a validated assessment tool often used in secondary care. It can be performed in under a minute and helps support the diagnosis.12 Currently there is no gold standard investigation to confirm LPR.
Lifestyle and dietary modifications
Dietary and lifestyle changes can be used as the as primary treatment in cases of mild LPR,13 or in combination with medication.14 Outline lifestyle and medication options as part of shared decision making with the patient.
Proton pump inhibitors
Proton pump inhibitors (PPIs) are an effective treatment for LPR.1415 Two systematic reviews and meta-analyses concluded they are more effective than placebo, but heterogeneity in study designs makes comparisons difficult and there is still uncertainty over how effective PPIs are in managing LPR. The superiority of one PPI over another in treating LPR is also not established. There are no nationally agreed treatment recommendations for using PPIs to treat LPR, but typical regimens are twice daily dosing 30-60 minutes before meals for three months. This practice contrasts with NICE guidance for the treatment of GORD, which includes a full-dose PPI for four or eight weeks, with an option of H pylori test before starting the PPI.
Sodium alginate liquids provide a mechanical anti-reflux barrier within the stomach. They are commonly recommended for LPR, but there is only low quality evidence of their efficacy.16 In patients with severe symptoms or only a partial response to PPI, alginates can be taken before bedtime in addition to a PPI. As monotherapy or for those who experience side effects with PPIs, alginates are commonly recommended at one dose three times a day. Alginates are available over-the-counter as a liquid or chewable tablets.
H2 antagonists are less effective at controlling LPR symptoms than PPIs or sodium alginate.17 They are recommended as a second line treatment for those with only a partial treatment response to and who cannot tolerate PPIs or sodium alginate. In 2019 some branded and generic versions of ranitidine was found to contain the carcinogen N-nitrosodimethylamine, and the UK Medicine and Health Regulation Agency issued a recall of the ranitidine-based drugs Zantac and Perrigo in October 2019.18 Alternative H2 antagonists, such as cimetidine, are still available.
Follow-up and referral
Follow-up and referral should be tailored to the individual. For most patients, we recommend a four week follow-up to assess response to treatment, monitor weight and reassess lifestyle modifications. Some patients with no risk factors may choose to seek follow-up only if their symptoms persist after treatment.
In those with no response or worsening symptoms, check lifestyle and medication adherence, review the diagnosis, and consider referral to an ENT outpatient clinic for endoscopic examination of the throat.
In those with only a partial response, discuss whether to continue with existing medication, try a different medication, or refer for an ENT assessment.
In those with complete resolution of symptoms, stop PPI treatment at three months. Patients who have recurrent symptoms of LPR after a trial without PPIs can consider long term PPI therapy after discussion of the potential long term risks and alternatives such as alginates and dietary modifications.1920
Education into practice
How might you explain to a patient how the symptom of a “lump in the throat” is caused by laryngopharyngeal reflux?
How do you explain globus symptoms to a patient who is worried about cancer?
Consider auditing repeat PPI prescriptions in patients with LPR as part of deprescribing reviews
How this article was made
We made a literature search via Medline and Google Scholar using the search term “Laryngopharyngeal reflux OR acid reflux OR globus pharyngeus.” We also searched the Cochrane Library for relevant reviews.
How patients were involved in the creation of this article
No patients were involved in the creation of this article.
This is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.
Contributors: NH wrote the original draft. All authors were responsible for conception of the article and reviewing and editing drafts.
Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare
Provenance and peer review: Commissioned, based on an idea from the author; externally peer reviewed.
The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd to permit this article (if accepted) to be published in BMJ and any other BMJPGL products and sublicences such use and exploit all subsidiary rights, as set out in our licence (https://authors.bmj.com/policies/#copyright).”
- Koufman JA
. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope1991;101(Suppl 53):1-78. doi:10.1002/lary.1991.101.s53.1 pmid:1895864
- ↵Pan London Suspected Cancer Referral Guide. 2017. https://www.healthylondon.org/wp-content/uploads/2017/11/Pan-London-Suspected-Cancer-Referral-Guide-Upper-GI.pdf.
- ↵National Institute for Health and Care Excellence. Suspected cancer: recognition and referral (NICE guideline NG12). 2020. https://www.nice.org.uk/guidance/ng12.
- ↵Medicines and Healthcare products Regulatory Agency. Ranitidine – MHRA drug alert issued for Teva UK recall. 2020. https://www.gov.uk/government/news/ranitidine-mhra-drug-alert-issued-for-teva-uk-recall.
. Proton pump inhibitors. 2015. https://bnf.nice.org.uk/drug-class/proton-pump-inhibitors-2.html.This article is from The BMJ – https://www.bmj.com/content/371/bmj.m4091