Reflux Hypersensitivity

Some patients are more sensitive to reflux than others.

For instance, some people might have light reflux but severe symptoms. They might go to the doctor, who carries out 24-hour pH monitoring. The test might only show light reflux despite the fact they have significant heartburn.

This phenomenon is called esophageal hypersensitivity, or reflux hypersensitivity.

Based on feedback from Refluxgate followers, I know it can be tedious to find the right information, diagnosis, and treatments for esophageal hypersensitivity. 

I spoke to Professor Arjan Bredenoord to find out more.

Interview On Reflux Hypersensitivity

Gerrit Sonnabend: What is your professional background?

Prof. Arjan Bredenoord: I’m a gastroenterologist, and I work in an academic medical center in Amsterdam, Netherlands. It is a university hospital. I do patient care, but I also teach and do scientific research. My main focus lies in benign esophageal diseases like reflux, eosinophilic esophagitis, and achalasia.

I read that you also have a particular interest in neurogastroenterology and gastric motility. How does looking through those “lenses” change your perspective on reflux?

Thanks for the question. I am a professor of Neurogastroenterology and Motility at the University of Amsterdam. Essentially, that is the study of nerves, sensitivity, and movements of the gastrointestinal tract.

In reflux disease, I study the sensitivity of the esophagus. This is very important because some patients feel reflux clearly coming up while others do not. People’s sensitivity to reflux varies.

Many patients simply have a lot of reflux. In that case, it is obvious why they feel the symptoms. However, some patients have normal amounts of reflux. Yet they still have very intense or very frequent symptoms. You cannot explain it by the quantity of reflux alone. That type of patient seems to be more sensitive to reflux.

That brings us to the main topic that I wanted to talk with you about in this interview: Sensitivity to reflux. What is the medical term for that? Reflux hypersensitivity?

Reflux hypersensitivity is indeed the right term. It means patients do not have an abnormal quantity of reflux, but still have reflux symptoms.

Their esophagus is more sensitive to reflux.

I want to make sure people really understand the basics before we advance deeper into the topic. In a few simple sentences, can you explain what hypersensitivity is? How do you explain hypersensitivity to patients?

Patients who are hypersensitive experience painful sensations to normal stimuli that do not really damage the organs.

Let’s take the bowels as an example. It is normal that after people have eaten, the bowels start contracting to help with digestion.

Now, most people will never feel this. They have no clue that their bowels are moving and working. But there are patients with irritable bowel syndrome. They have hypersensitive bowels, and they constantly feel their bowels moving. Sometimes it is even a painful sensation. They feel cramping despite the fact their bowels are just working on their normal daily digestion work.

Do you have a similar example of how patients experience reflux hypersensitivity?

We did an experiment in which patients with reflux hypersensitivity were compared with subjects that did not have any symptoms of reflux disease. We placed a small catheter through the nose of these patients into their esophagus and slowly dripped an acidic solution into the esophagus. Not enough to cause any damage.

The healthy subjects never really felt this acid dripping into their esophagus. Or at most, they got mild sensations.

However, the patients with reflux hypersensitivity quickly felt acid in their esophagus. Sometimes it triggered very intense pain behind the breastbone. So, it seems that their nerves are easily triggered. That’s why they feel the reflux much quicker and more intensely.

So, essentially, being hypersensitive means that your reaction to reflux is much stronger than usual. You can experience symptoms even while just having very weak reflux.

Yes. They have symptoms due to reflux, but the volume of reflux that causes the symptom is much smaller than in other patients. So even small amounts of reflux can sometimes cause severe symptoms.

Why does somebody get esophageal hypersensitivity? What is the physiological mechanism behind it?

We don’t know exactly, but several hypotheses have been suggested.

One of the things happening is that the nerves are more easily triggered. It could be that they are activated even by small amounts of reflux.

Another reason could be that there are very small lesions in the wall of the esophagus that you cannot see with a normal endoscope, and that leads to easier diffusion of the acids to the nerves. Meaning, the reflux reaches the nerves more easily.

Some people have suggested that the nerves might be more superficial – closer to the surface.

Those could all be potential explanations for hypersensitivity.

Is esophageal hypersensitivity something that you are born with? Or does it develop over time? Can it improve?

Often, what you see is that it comes and goes.

There are some theories about hypersensitivity. When we talk about hypersensitivity in the bowels, it sometimes happens after bacterial or viral gastroenteritis. Patients have diarrhea for one or two weeks. The bacteria are attacked by the immune system and are killed. However, sometimes people keep having these symptoms, and they develop this hypersensitivity. Somehow, the inflammation has triggered the hypersensitivity.

The same might happen in the esophagus. Sometimes patients have a period where they have a lot of reflux. The reflux then goes back to normal, but then they still have this hypersensitivity.

Factors such as stress can play a role as well. I am not saying that stress is the cause of the symptom, but it can certainly aggravate things. We all know situations like that. A student might be stressed due to studying a lot for an upcoming exam and experience stomach pain. Children can have pain in their belly the day before their birthday. We know that our emotions sometimes play a role in abdominal sensations.

What about the diagnosis? What is the process to diagnose a patient with reflux hypersensitivity?

If a patient has reflux symptoms, most gastroenterologists will start with an upper endoscopy. Only a minority of reflux patients have visible abnormalities. So, the endoscopy is not so much done to diagnose reflux, but rather to exclude other diseases that might cause the patient’s symptoms.

When the endoscopy is negative, and you want to make sure that the patient’s symptoms are due to reflux, you will need to do reflux measurements. If the outcome is that there is a normal amount of reflux, but you can see that symptoms are clearly related to the reflux, then you are certain that there is reflux hypersensitivity.

If I understand correctly, the diagnosis is made by excluding other possible causes of the symptoms? If somebody has significant heartburn, but no unusual amount of reflux or other visible causes for the symptoms, it would be diagnosed as esophageal hypersensitivity?

Well, we like to study the symptoms that patients have during the 24-hour measurements and then see if reflux occurs immediately prior to the symptoms. If that happens, you have a very strong indication that the reflux and the symptoms are causally related.

The patients log the symptoms during the 24-hour test. They can write it in a diary with the exact time it happened, or they can press a data recorder. The computer software can then later calculate what happened two minutes before patients perceived their symptoms.

We talked before about those different possible causes of reflux hypersensitivity. What about treatments? Are there any treatments that specifically target those causes?

First off, reflux obviously plays a role here. If you can reduce reflux, it is likely that the symptoms will be reduced as well.

A simple solution is proton pump inhibitors — drugs like omeprazole and pantoprazole. Now, usually, patients with hypersensitivity have already tried these drugs. So, you need to try to reduce reflux in other ways.

Another thing you can do, if patients have a lot of nocturnal symptoms, is sleep position therapy.

If there is significant stress in a patient’s life, it’s also possible to approach that part of the problem. You could look into stress-reducing treatments.

Dietary habits can play a role in the provocation of reflux as well, so avoiding coffee, large high-fat dinners, orange juice, and smoking can be helpful as well.

Finally, there are also medications that make the nerves of the esophagus less sensitive, to reduce the pain.

Can you talk a little bit more about those medications for the pain?

Typically, medicines that are often used are citalopram, amitriptyline, or nortriptyline, in a low dose. They reduce hypersensitivity.

The drugs take a while before their effect kicks in. Many patients only notice a beneficial effect after months of usage.

There are also disadvantages. For example, amitriptyline can cause dizziness and dry mouth, particularly in the first few weeks.

People will first have side effects. The beneficial effect will only occur later. It is sometimes difficult for patients to persist and adhere to the medication, particularly when they have side effects but do not see any beneficial effects in the first few weeks.

You mentioned amitriptyline as an example, which is a tricyclic antidepressant. Do you essentially use the same types of medication for hypersensitivity as for neuropathic pain, meaning pain from nerve damage? I know that for neuropathic pain, tricyclic antidepressants, as well as antiepileptics like pregabalin, are typically used.

Yeah, pregabalin is often used, but in my country, we mainly use citalopram and amitriptyline. Pregabalin is often used, for example, in the UK and the US.

Do any of those medications work particularly well for esophageal hypersensitivity? Or does it come down to the treating physician’s preference?

It is a preference. Also, the drugs are not registered [off-label use] for this indication.

Understood. Let me try to sum things up. If you have symptoms due to reflux hypersensitivity, it means you still have reflux – and that you react to it with unusually strong symptoms. You still want to try to reduce the reflux with the usual reflux treatment methods.

If you want to do more against the pain, you can use specialized nerve pain medications. However, those might give you more side effects than normal reflux medications.

Yes, that is correct.

There is one thing I want to bring up, because I sometimes get emails that highlight a problem when it comes to communication between patient and doctor regarding reflux hypersensitivity. This is just anecdotal. I don’t know how common this problem is.

Followers sometimes tell me that they have seen their gastroenterologist, had all the testing done, and the doctor tells them: “You don’t really have reflux, this can’t explain your heartburn”, and prescribes them antidepressants. Now my reader tells me that apparently, their doctor thinks it is all in their head and that they are imagining things. I don’t know if that’s really how those readers’ doctors are explaining the issue to them, but it is how many patients seem to interpret the conversation.

How can you avoid patients thinking their physiological problem is not taken seriously, because their gastroenterologist prescribes them an antidepressant?

Yeah. I can imagine this can be an issue.

It is very important for patients to realize that if they have reflux hypersensitivity, the trigger starts in the esophagus, travels through the nerves and goes to the brain, and that makes people conscious of a symptom.

If people are prescribed these medicines, for example citalopram or amitriptyline, the aim of the medicine is not to change their mood, but to focus on the sensitivity of the nerve.

I agree that it is very important to explain that. Also, to explain that it is not just stress and not just all in their head. And I also think that it can even cause damage if you do not give a good explanation, because people may have the feeling that it’s all their fault, which is, of course, not the case.

End of Part #1 of the Interview

This was just the first part of the interview.

I also talked with Professor Bredenoord about the LEFT device, which promises to reduce nighttime reflux by conditioning users to avoid sleeping on their right side.

Gerrit Sonnabend
 

Gerrit is a German data scientist & medical publisher. His formal education is in qualitative research. He had severe reflux himself. Read more about him here.