Gastro-oesophageal reflux disease

Description

Phenotypes - they behave differently and respond differently


Erosive oesophagitis	Visible breaks. Los Angeles grade A-D
Non-erosive reflux disease (NERD)	~70% of symptomatic patients - normal endoscopy with abnormal acid exposure
Reflux hypersensitivity	Normal acid exposure, symptoms correlate with reflux events
Functional heartburn	Normal acid exposure, no symptom correlation. PPI-unresponsive by definition
Barrett oesophagus	Intestinal metaplasia - see separate note

*A normal endoscopy does not exclude GORD* - roughly 70% of symptomatic patients have a macroscopically normal oesophagus
Los Angeles grade C/D is diagnostic of GORD without further testing

Weekly heartburn in ~15-20% of Western adults
Risk factors: older age, central obesity, hiatus hernia, pregnancy, smoking, alcohol, scleroderma, asthma
**H. pylori is negatively associated with GORD* - eradication can unmask or worsen reflux (atrophic gastritis reduces acid output)*
Infant reflux: physiological, peaks ~4 months, resolves in ~90% by 12 months

Mechanism

Transient lower oesophageal sphincter relaxation (TLOSR) is the primary mechanism - not low resting LOS tone
Hiatus hernia contributes two ways:

1. Displaces the diaphragmatic crura, which normally reinforce the sphincter during inspiration, coughing and straining

2. Loses the intra-abdominal segment of oesophagus that acts as a pinch valve

Also: delayed gastric emptying, impaired oesophageal clearance/peristalsis, acid pocket at the GOJ, inc intra-abdominal pressure (obesity, pregnancy)
Scleroderma - aperistalsis + incompetent LOS -> severe reflux and stricture

Drugs that aggravate GORD

dec LOS tone: beta-agonists, theophylline, anticholinergics, TCAs, progesterone, alpha-blockers, diazepam, calcium channel blockers, nitrates
Direct mucosal injury (pill oesophagitis): aspirin/NSAIDs, doxycycline, quinidine, bisphosphonates, potassium chloride, iron
- Take with a full glass of water and stay upright for 30 minutes

Typical symptoms

Heartburn and regurgitation - the two typical symptoms; response to a PPI trial supports the diagnosis
Hiatus hernia specifically: post-prandial fullness and upper abdominal pain
Sandifer syndrome - paediatric reflux with food refusal and neck/back arching mimicking a seizure or dystonic reaction

Extra-oesophageal (weaker association - do not over-attribute)

Chronic cough, hoarseness/laryngitis, asthma, dental erosion, globus, non-cardiac chest pain
Always exclude cardiac chest pain first

Alarm features -> endoscopy

Investigations

Empirical PPI trial is the appropriate first step in typical symptoms without alarm features - cost-effective
- Failure to respond -> investigate, do not escalate empirically
Gastroscopy - erosions, stricture, Barrett, and to exclude malignancy; take off PPI 2-4 weeks before if confirming the diagnosis
Ambulatory pH or pH-impedance monitoring - the reference test
- Off PPI if confirming GORD in unproven disease; on PPI if proven GORD with refractory symptoms
- Gives acid exposure time and symptom association
High-resolution manometry - before anti-reflux surgery, and to exclude achalasia or a major motility disorder
Barium swallow - only for anatomy (large hernia, stricture), not diagnosis

By severity and phenotype

A. Lifestyle - for everyone

Weight loss - the intervention with the best evidence
Elevate the head of the bed; avoid eating within 3 hours of lying down
Smoking and alcohol reduction
Avoid identified trigger foods individually - blanket dietary restriction is not supported
Review the aggravating drug list above

B. Acid suppression

PPI once daily before breakfast for 4-8 weeks
- Take 30-60 minutes before a meal - it needs actively secreting pumps
- The single commonest reason for "PPI failure" is taking it at bedtime or with food
Erosive oesophagitis LA grade C/D, stricture or Barrett -> continue maintenance PPI
NERD -> step down to the lowest effective dose, or on-demand therapy
H2RA (famotidine) - adjunct for nocturnal breakthrough; tachyphylaxis within days
- Ranitidine was withdrawn worldwide (2019-20, NDMA contamination) - famotidine is the current H2RA
Alginate (Gaviscon) - post-prandial and pregnancy
Potassium-competitive acid blockers (vonoprazan) - available in some countries; faster, more sustained acid suppression
Deprescribe: taper rather than stop abruptly - rebound acid hypersecretion

C. Refractory symptoms - re-examine the diagnosis first

Confirm adherence and dosing timing
pH-impedance on therapy - separates persistent acid reflux, non-acid reflux, reflux hypersensitivity and functional heartburn
Consider eosinophilic oesophagitis, achalasia, rumination, gastroparesis, cardiac disease
Functional heartburn / hypersensitivity -> neuromodulator (low-dose TCA, SSRI), not more acid suppression

D. Surgical / endoscopic

Laparoscopic fundoplication - for proven GORD with volume regurgitation, PPI intolerance, or patient preference
- Requires manometry first (fundoplication over an unrecognised achalasia or aperistalsis is a disaster)
- Adverse effects: dysphagia, gas-bloat, inability to belch or vomit
Magnetic sphincter augmentation; endoscopic fundoplication in selected patients
Bariatric surgery (Roux-en-Y gastric bypass) - the preferred operation when obesity and GORD coexist; sleeve gastrectomy worsens reflux

E. Infants

Formula thickening as an initial measure; positioning, smaller more frequent feeds
Trial of extensively hydrolysed formula if cows' milk protein allergy suspected
Acid suppression is over-used in infants - reserve for proven oesophagitis or complications

Chronic and relapsing; most patients need long-term or intermittent therapy
NERD rarely progresses to erosive disease
Barrett develops in ~10-15% of chronic reflux patients; progression Barrett -> dysplasia -> adenocarcinoma is slow (~0.3-0.5%/yr without dysplasia)

Complications

Long-term PPI harms - real but modest

Hypomagnesaemia, B12 and iron malabsorption
Enteric infection and C. difficile
Fundic gland polyps; interstitial nephritis; fracture risk
Association, largely not causation - but a reason to use the lowest effective dose and review the indication annually

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