Reflux oesophagitis - ulcers due to reflux

An area of ulceration at the junction between the oesophagus and the stomach

Reflux oesophagitis - ulcers due to reflux

Heartburn is the symptom of “burning discomfort” behind the “breastbone”.

• Heartburn results from acid in the oesophagus.
  • The stomach is designed to handle acid but the oesophagus has a different lining and is more sensitive to the effects of acid.
  • This sensitivity to acid varies significantly from person to person.
• The basic abnormality is weakness of the valve between the oesophagus and the stomach.
  • This "valve" is designed to allow food into the stomach but to prevent acid and food refluxing back into the oesophagus.
  • Weakness of the valve (sphincter) does not improve over time; in fact - it may tend to weaken further over the years.
  • This “valve” function is adversely affected by a hiatus hernia. A hiatus hernia is when the top part of the stomach is sitting up in the chest instead of being below the diaphragm. This causes the valve to be working at a disadvantage (not as effective for reasons that are not entirely clear).
    
    
• Reflux may be aggravated by
  • fatty foods; spicy foods
  • alcohol
  • smoking
  • chocolate
  • peppermint
  • caffeine
• Some drugs can aggravate reflux;
  • Asthma treatments.
  • Anti-inflammatory drugs.
  • Calcium channel antagonists - given for high blood pressure.
• Stress does not cause reflux but can make the symptoms more distressing.

From left to right increasing signs of reflux laryngitis. There remains doubt about how useful this change is in diagnosing throat symptoms that may be due to reflux

There can be a lot of redness and swelling in the larynx and surrounding areas - arytenoid folds. It is tempting to blame these changes on acid reflux but this appears not be the cause most of the time

Symptoms

• Acid reflux becomes more common after the age of 40 years.
  • This may be because of gradually weakening of the “valve”.
  • Weight gain is common in the middle years (particularly around the waist which may increase the pressure on the stomach).
  • Even modest weight gain can lead to new symptoms in susceptible people.
  • Once heartburn becomes a troublesome symptom for a given individual it may wax and wane in intensity but spontaneous remission is uncommon.

• Heartburn is very common.
  • 35% of the population have heartburn more once per month.
  • 7% have daily episodes.

• The typical symptoms are;
  • Heartburn - a burning sensation behind the breastbone. This commonly occurs 1-2 hours after a meal (particularly larger fatty meal).
  • Regurgitation- the easy flow of stomach contents (acid and food) into the back of the throat.  This is different from vomiting.  There may be a sour or bitter taste in the mouth
  • Belching.   Not all belching is associated with reflux - this can be due to air swallowing.  Excess belching can be due to excess fermentation in the small bowel - excess fibre should be avoided.

• Less common symptoms (not "typical")
  • Hoarseness, sore throat, repetitive throat clearing, cough, choking sensations.
  • These symptoms can be caused or aggravated by reflux but there are many other causes and review by an ENT specialist is usually required.
  • Acid reflux is often blamed for many throat problems but the response to acid lowering treatment is often disappointing.
  • If there are no symptoms of heartburn or acid regurgitation then it is unlikely that acid reducing treatment will have any effect. pH studies (see Tests) can often help sort out whether acid reflux is involved.
    
    
  • The symptom of "lump in the throat" sometimes given the name of "globus" is rarely due to reflux. All tests are generally normal. Sometimes oesophageal pH testing is required to prove that there is no acid reflux. This symptom may be related to stress.  It commonly follows a stressful life event, often lasting for several months , then settling without treatment.  There is no value in taking acid reducing medication such as omeprazole. 
  • Asthma. Reflux is common in asthmatics. However, the response to acid lowering treatment (in terms of improved asthma control) is usually modest.
  • Sometimes reflux is the underlying cause of chest pain. The term "chest pain" means a more generalised chest discomfort or pain rather than just a burning sensation behind the breastbone. Initial investigations may have focused on the heart.
  • If these tests are normal the term "non-cardiac chest pain" is used. In this setting acid reflux is the explanation for the pain about half the time. If there is no response to treatment to reduce acid then a drug called amitriptyline can work - the theory is there is hypersensitivity of some structures in the chest. Often oesophageal pH monitoring is required (see Tests).

• Any symptoms of difficulty swallowing, pain on swallowing or weight loss needs further assessment by gastroscopy without delay.

Probe and recorder for oesophageal pH monitoring

Probe and recorder for oesophageal pH monitoring

Probe inserted through the nose - connected to minirecording device

Investigation / tests

• Gastroscopy is the most important test.

  • Gastroscopy is best performed before starting treatment however, some value from the test at any stage during treatment.
  • The presence of ulceration at gastroscopy (called reflux oesophagitis) suggests more severe disease.
  • 50% of people with symptoms suggestive of reflux will have a normal endoscopy. Troublesome symptoms can occur even if the gastroscopy is normal. 
  • Larger hiatus hernias are associated with more severe disease.  Small hiatus hernias are of less importance.  The appearance can vary from one examination to another (a sliding hiatus hernia – variable size). 
  • If the gastroscopy is normal then a diagnosis of acid reflux can be made if there is a suggestive history of heartburn and a good response to treatment
  • An important potential finding at gastroscopy is Barretts oesophagus (see section on long-term problems).

• Oesophageal pH monitoring is an investigation that may help resolve some uncertainty about the diagnosis.
  • This test is a direct measure of the amount of exposure of the oesophagus to acid over a 24-hour period. 
  • It involves passing a thin catheter through the nose into the oesophagus. This is secured in place and connected to a recording device.
  • At the completion of the test the pH recordings are downloaded on to a computer and a graph of pH over the day is produced.
  • The procedure allows for the correlation of chest pain / heartburn or other symptom with oesophageal acid exposure.
  • This test requires an initial specialist consultation.
  • This test can be performed on or off treatment with omeprazole or similar drug.
  • Performing the test off treatment is the most helpful to exclude or prove reflux. pH monitoring on treatment is performed using combined impedance and pH testing which allows detection of reflux even when there is no acid in the material that is refluxed into the oesophagus
  • It is available at the Mercy Specialist Centre, Epsom, Auckland (09 6301838).

Non-medication options - diet, lifestyle changes, antacids

• Life-style changes are important.

  • This approach tends to be ignored now that we have very effective medications but I think this is a mistake.
  • The presence of heartburn is a sign that the body is not “enjoying” the current eating pattern or other aggravating factors.
  • Smoking should be stopped. Unfortunately, there is often weight gain after stopping smoking and this may aggravate reflux.
  • Weight reduction is crucial.
  • Elevation of head of the bed is not helpful (and not well tolerated) for most people.
  • Treatment of constipation can help reflux.



• Dietary changes.

  • Reduce intake of fatty foods and reduce the volume/size of meals.
  • Reduce alcohol, spicy foods, carbonated drinks, coffee, chocolate, peppermint.
  • Citrus juice, and spicy foods (chilli) directly stimulate nerve endings in the oesophagus. Coffee and Coke are  'sensitisers' for the oesophagus (and rest of gut!)
  • Alcohol, peppermint - relax the lower oesophageal sphincter. Fatty foods stimulate more acid secretion.  Curry stimulates acid secretion.
  • Avoid eating late at night or night-time / pre-bed snacks.
  • If excess belching - decrease increase of fibre.
    

• Antacids

  • Antacids are relatively weak compared to other medications.
  • They can briefly neutralise gastric acid. The effect may only last for 30 -60 ins.
  • Gaviscon and Mylanta are simple and convenient treatments and can be tried first for infrequent mild symptoms.

What next if the medication doesn’t work?

• About 1/3 rd of people with symptoms suggestive of reflux to do not respond to the usual dose of Losec or Somac.
  • This may be may be due to inadequate control of acid. An increased dose could be effective.  This must be take regularly 30mins before breakfast and 30mins before dinner.  Many people take treatment on an intermittent basis but this is a lot less effective in reducing gastric acid
  • Some people simply do not respond to a PPI at any dose. Sometimes a switch of PPI is successful. Omeprazole on a mg for mg basis is more potent than pantoprazole

• The symptoms could be due to another problem and not due to heartburn (from acid reflux).
  • The diagnosis may need to be reviewed and specialist advice is usually required.
  • The diagnosis may be an over-sensitive oesophagus or functional heartburn.  This means it sounds like reflux but acid is not involved..This is why suppressing acid even with effective drugs does not relieve symptoms.
  • The symptoms may be due to irritable bowel syndrome or a motility disorder or stress could be playing a major role.
  • A sensation of a "burning mouth" or a lump in the throat are not usually caused by acid reflux.
  • Some people have chest pain that is not due to heart problems or due to acid reflux. The reason for this type of pain may be unknown.
  • Some chest pain can be part of a generalised musculoskeletal sensitivity called "fibromyalgia" - characterised by multiple trigger points.

• Sometimes the symptoms are due to a “sensitive oesophagus”.
  • There is acid reflux but it is relatively mild. However, because of the sensitivity of the oesophagus, it doesn’t take much acid exposure to cause troublesome symptoms.
  • This can be a difficult problem to manage.
  • It has some overlap with irritable bowel syndrome.
  • Sometimes the addition of amitriptyline at night is helpful.
  • It is very important to stop coffee and all alcohol and spicy food - these will all sensitize the oesophagus. 
  • Sometimes upper abdominal discomfort and bloating is mistaken for acid reflux but is actually IBS.  Dietary restrictions as for IBS may be appropriate
  • Constipation should be treated as this can aggravate reflux
  •  Lack of sleep,  depression and/or anxiety are all potential aggravating factors

Tightening the valve by folding part of the stomach around the lower part of the oesphagus

Tightening the valve by folding part of the stomach around the lower part of the oesphagus

The appearance from into the stomach looking up to the "valve' - junction between stomach and oesophagus

What is the role of surgery?

• Anti-reflux surgery (laparoscopic fundoplication) is an option for the people who have symptoms well-controlled on a PPI such as omeprazole or pantoprazole who do not wish to take long-term medication.
  • If the reflux symptoms have not responded to a PPI then careful evaluation by a gastroenterologist is required before considering an operation.
  • It is usually a mistake to think that "resistance to medical treatment" means that an operation is needed.  Usually there needs to be a rethink of the diagnosis
  • Oesophageal pH monitoring is an important part of the investigations before an operation is considered.

• There are some potential problems with the operation.
  • The operation may aggravate bloating and flatulence and cause an inability to belch.
  • For most people this is a minor problem but for some (1/4) it is a significant disadvantage of this operation.
  • Problems with bloating are worse in women and particularly if there has been some problems prior to the operation.
  • Irritable bowel symptoms may also be a risk factor for having troublesome bloating after an operation for reflux.
  • Difficulty swallowing is common over first 3-6 months but resolves in majority. Perhaps 1-2% continue to have troublesome problems with swallowing and need to have the operation revised or completely reversed.
  • Diarrhoea is a rare side-effect.

• The outcome of surgery.
  • This rated as good for 85%, average for 10%.
  • 5% are concerned enough about the adverse effects to be unhappy or ambivalent about outcome.
• The proportion of people who come off treatment in the long-term is variable in different reports.
  • Overall it seems that at least 30% (maybe up to 50%) of people continue treatment with a PPI after the operation.
  • This means that there may be some disappointment if one of goals of surgery was to "come off the medications".
• Safety issues.
  • The operation is comparatively safe however any operation and anaesthetic has a risk.
  • Reports suggest 1 death in 500-1000 operations.
  • About 5% will have some complication during the recovery period.
  • 2-3% will need a re-operation.
  • The effect of the operation may reduce over time.  Some loss of effect after 10-15 years is common

Barrets oesophagus is a change in the lining of the oesophagus - now a darker orange colour - this is more unstable and there a small but definite risk of changing to cancer of the oesophagus

A stricture or narrowiing of the oeophagus from scar tissue. This can be the result of long-standing ulcers

Barium swallow of a stricture

Long term problems from reflux

Barrett’s oesophagus

• This is a change in the lining of the oesophagus which results from long-standing reflux.
  • This change can occur with relatively mild symptoms.
  • Barrett's oesophagus often reduces the sensitivity of the oesophagus to acid leading to less heartburn.
    
  • The important aspect of Barrett's oesophagus is an increased risk of oesophageal cancer.
  • Careful specialist follow-up is required.
  • Repeat gastroscopy at a regular interval will usually be recommended.
  • The risk is greater for men and if there are more extensive changes in the oesophagus.Being significantly overweight and smoking increases the risk. Smoking and heavy alcohol intake are also risk factors for getting cancer of the oesophagus.
  • Multiple biopsies are taken from the oesophagus to check for a change called dysplasia.
  • This finding implies some instability of the lining of the oesophagus and an increased likelihood of progressing to cancer of the oesophagus.
  • If the changes are called "high grade" then surgery may be recommended to prevent the possible progression to oesophageal cancer.
  • Other endoscopic techniques are being developed.  HALO is the most promising technique - now available in main centres in NZ
    
  • Long term treatment with Losec (or similar medication) will be recommended but this is not enough to prevent possible progression to cancer.
  • If you have any problems with swallowing then urgent gastroscopy is required.

Oesophageal stricture

• This is a narrowing in the oesophagus as the result of inflammation, ulceration and eventually scarring in the oesophagus – all due to acid reflux.


• This leads to difficulty swallowing.
  • Treatment with Losec (omeprazole) or Somac (pantoprazole) will improve the symptoms.
  • Often a dilatation of the oesophagus is required (performed at the same time as a gastroscopy).
  • Sometimes more than one dilatation is required.

Lump in the throat sensation

• Having a lump in the throat sensation is normal with an intense emotional experience.


• Having a persistent sensation of a lump is also common.
  • Up to 15% of people in survey stated that they had experienced this symptom in the last year
  • The medical term is "globus".


• The cause is unknown.
  • However, there is clearly an association with stressful life events.
  • No abnormality of the throat or oesophagus can be shown.
  • The "globus" is often better with swallowing. i.e this symptom is NOT related to blockage of the oesophagus
  • There is no treatment but it always settles (eventually!).
  • A gastroscopy examination will provide reassurance.

Medication

• H₂-antagonists such as ranitidine (Zantac) and famotidine (Pepcidine).

  • They are effective for mild symptoms.
  • They are often the best choice for “as required” treatment.
  • There is rapid onset of relief (within 30mins).
  • The effect tends to weaken with regular use therefore intermittent treatment "gets the best out the drug".
  • The dose available in “over-the-counter” preparations is relatively small therefore less effective than a prescription for the same medication.
  • Zantac has recently been withdrawn worldwide (2019) because of concerns with the manufacturing process.  It is not clear if this will be available again
  • Famotidine was withdrawn from the NZ market but will need to be reintroduced as the preferred medication in this class.

• Proton pump inhibitors.

  • Proton pump inhibitors (PPI) such as omeprazole, lansoprazole and pantoprazole are very effective in control of gastric acid secretion over the 24-hour period. They have become the mainstay of treatment of reflux.
  • There are other options in this class - the above are currently available in NZ. They are all generics - that is not the origin brand and manufacturer  - there is no evidence of any problem with this swapping process - the cost saving has been very significant.
  • There are some differences in potency of these PPIs  - the best is rabeprazole or eso-omeprazole (not available in NZ. Omeprazole is more potent than pantoprazole (mg for mg).
  • Switching from one PPI to another PPI is occasionally helpful  - dosing changes as below are the first option
  • A single morning dose is usually sufficient but 1/3 of people will need a second dose before the evening meal.
  • Remember that omeprazole and pantoprazole are most effective if given 30 mins prior to meals. This means that the optimal dosing is 30mins before breakfast and then 30mins before dinner. The commonest error is to take the evening dose last thing at night.
  • Absorption is not as good when taken with (or after) the meal.
  • It is more effective to split the dose (e.g omperazole 20mg twice daily) rather than to take 40mg in the morning. A small proportion of people (<20%) are able to get a good effect from lower doses. e.g omeprazole 10mg daily or 20mg every 2nd day.
  • These tablets should be taken long-term if significant oesophagitis (ulceration) was observed at endoscopy.
  • There is increasing confidence that omeprazole and pantoprazole are safe during pregnancy. A large number of pregnancies have been reviewed. There is no increase in risk of birth defects. Omperazole does cross the placenta more than pantoprazole.

What about the long-term view of treatment?

• If you have daily symptoms of heartburn then regular daily medication is required for adequate relief of symptoms.

• • If the symptoms are less frequent then many people can have intermittent treatment.
    • This may be using omeprazole, lansoprazole or pantoprazole.
    • Another option is to accept the less powerful treatment with H₂-antagonists (famotidne) and concentrate on lifestyle modifications. These tablets are best designed for "as required" use. They have the advantage of rapid onset of action.
    • The long-term goals should be to lose weight, eat a better diet with lower fat content, stop smoking and moderate alcohol consumption.
    • This must also be good for overall health and lead to reduced risk of heart disease.
    • If some success is achieved with above life-style changes then reduction in dose or stopping medication may be possible.
    • Otherwise it is usual to have the same symptoms again within a few days of stopping medication. Sometimes long-term treatment in younger people is accepted when more intermittent treatment might work.
    • There can be an apparent increase in symptoms during the first week after stopping regular medication. This may be due to an increase in sensitivity of the oesophagus while on effective treatment or perhaps a temporary rebound in acid secretion.
    • There has been a dramatic increase in the use of PPIs over the last 20 years. Some of this relates to appropriate use but many people are better to concentrate on life-style changes rather than to rely on medication.

Is long-term treatment safe?

• The main safety concerns with proton pump inhibitors have been the theoretical concerns about long-term reduction in acid secretion or put another way - why do we need acid?
• Several studies of long-term treatment (now over 35 years) have now been reassuring. However new questions are being now being asked about drug safety.  There is now a reluctance to take daily medication because of anxiety regarding PPI side-effects reported in popular press.
• Some issues can be predicted as possible consequences of longterm acid suppression.  Other issues are surprising and the possible biological mechanisms are debated.
• Many studies have been retrospective analysis of databases. There is difficulty in eliminating residual bias in observational studies because all confounding factors may not be recorded
• Biological plausibility should always be considered when looking at “new” findings of possible adverse effects
• Digestion is not affected by the suppression of normal acid secretion. Surprisingly acid is not essential for the normal digestion of food. There may be a marginally lower level of vitamin B12 - but this has been shown to be clinically relevant.
• There have been recent reports of increased risk of fracture.  There appears to be a smalll risk but no evidence of osteoporosis - thinning of bones. 

• Magnesium deficiency has been reported. This presents as extreme fatigue and muscle weakness. This is more likely if also dehydration from diarrhoea or with also taking diuretics (fluid loss tablets).

• A cohort of new users of PPI treatment followed for a median of 5.71 years showed that there was an association between PPI use and an increased risk of all-cause mortality (hazard ratio 1.25 (1.23–1.28)).⁷ This is a small effect with many potential confounders and there is no clear biological mechanism for this association
• Several retrospective studies have shown conflicting results for an association of PPI with dementia. A recently reported prospective population-based study clearly indicated that PPIs use was not associated with the dementia risk, even for people with high cumulative exposure
• Many of these safety concerns will be proven to be misleading once better studies are published however there is enough data to cause a careful review all prescribing to ask if long term treatment is really necessary.
• Drug interactions can occur with omeprazole - particularly with Warfarin.