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Lin Chang, MD: Hello. I'm Dr Lin Chang. Welcome to Medscape's InDiscussion series on irritable bowel syndrome (IBS). Today we'll be discussing overlapping conditions with IBS with Dr Magnus Simrén. Dr Simrén is a professor of gastroenterology at the Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, at the University of Gothenburg. Welcome to InDiscussion, Magnus. It's so great to have you join us today. You're so knowledgeable in the field and one of the leaders in our field. I first want to start off by asking you, how did you become interested in IBS?
Magnus Simrén, MD, PhD: First of all, thank you for having me on the discussion. It is a pleasure to discuss this with you, Lin. Why did I become interested in IBS? It's a bit of a coincidence, actually. I started off as internal medicine doctor, and then I decided that I wanted to be a gastroenterologist and started doing research. By coincidence, they asked me to start a project on IBS, and there it was — that's how it started. I met the right people who steered me in the right direction. I don't regret it at all. It's been a wonderful area to work in.
Chang: And now many people are following in your footsteps. You've been a great mentor to many people. I'm going to start by talking about IBS in particular and its overlap with other conditions. We know that IBS can coexist with gastrointestinal conditions and it can also coexist with nongastrointestinal conditions, where patients have what we call extraintestinal symptoms. I first want to ask you about the coexistence of IBS and other gastrointestinal disorders like GERD (gastroesophageal reflux disease), which is very common, inflammatory bowel disease (IBD), and celiac disease. Can you tell us about the overlap with these types of conditions?
Simrén: Yes. There is this overlap between what we call organic gastrointestinal disorders within functional gastrointestinal disorders or disorders of gut-brain interaction (DGBI), as we prefer to call them today, among which IBS is one of the most common. This overlap is very common for all these conditions. If I start off with IBD, I'll see colitis or Crohn's disease. If you look at those patients when they are in remission, when there are no active signs of inflammation, still a considerable proportion of the patients report gastrointestinal symptoms compatible with IBS. Up to a third of these patients report ongoing symptoms compatible with IBS, despite no sign of active inflammation. This is a very common clinical problem. If you look at celiac disease, the story is the same there. If you look at celiac disease patients where the mucosa is healed after they started off with their gluten-free diet, roughly a third also report gastrointestinal symptoms. It's quite frequent that this is compatible with IBS but also with other disorders of gut-brain interaction. What is common for both the overlap between IBD, IBD and IBS, and celiac disease and IBS, is that there is an overlap with psychological comorbidity there as well. It seems to be an important factor in driving the symptoms, the link with psychological comorbidity. When it comes to reflux disease, the overlap is also common. It's been reported that there is a 30%-40% overlap between the two. Within these organic conditions, having IBS-like symptoms is very common.
Chang: It seems like there are two steps in managing a patient. When they first come in, you have to determine whether they have IBS, IBD, or celiac. When you establish that they have IBD or celiac, then the other issue is, could they have the overlap? Like you said, the IBD or celiac could be in remission and they could still have IBS. How do you think that occurs?
Simrén: We don't really know, but there are some theories that having inflammation can increase the sensitivity in your gut and create some kind of memory in the gut, so that what's happened before is there all the time. The brain can be involved as well. You can have brain-gut interactions playing a role in the symptom generation of having more chronic symptoms despite the fact that the inflammation is not active right now. We don't know the exact mechanism, but the inflammation probably plays a role.
Chang: You mentioned psychological symptoms playing a role in having these comorbid or coexisting conditions. How do you think that plays a role in predisposing someone to get IBS? Or do they get these conditions and they get some symptom-related anxiety or other symptoms? How do you see that?
Simrén: I think it can be both. I think we know now that there is a bidirectional interaction. We've known for a long time, but it's more appreciated now that there is a bidirectional interaction between the brain and the gut. I guess it goes both ways. Psychological factors can predispose you to these conditions or this overlap, but also the other way around. Having chronic gastrointestinal symptoms may predispose you to develop psychological symptoms. The important thing, from a clinical point of view, is that there is this overlap, so you need to address both when you treat the patients.
Chang: For IBD, I've seen this even in people who are close to remission or have just microscopic inflammation, and they keep getting treated with different IBD types of agents. Acknowledging or recognizing that they could have IBS as an overlap, would you consider treating them differently?
Simrén: I think so. If you don't see any inflammation, we should not treat for inflammation aggressively because there are a lot of side effects. We should probably then move more toward what we can call IBS-like treatments or IBS-type treatments, even though there are very few formal studies supporting this. This is more logical than to treat visceral hypersensitivity, brain-gut interactions, and so forth. That's more logical when we're in that stage.
Chang: Because you couldn't continue the IBD treatment — for example, the gluten-free diet for celiac — if you think the symptoms are due to more like an IBS or DGBI than the whole organic disease. I want to touch on GERD and IBS because GERD is in the esophagus, but many patients have lower GI symptoms. It's potentially not the same pathophysiology as IBD or celiac; it's just that these two conditions are very common. Is that why you may see it in one individual?
Simrén: Part of the overlap is probably due to being two very common disorders. But again, if you look at the literature, there is some support for this overlap being more than just two common disorders. The brain-gut interactions might play a role, the same type of mechanisms, underlying symptom reporting, symptom perception, etc. So maybe a more sensitive gut is processing central nervous system information from the gut differently than in other individuals.
Chang: That's a great point. Patients' perception of their symptoms may be somewhat amplified; there's more attention to them and they're more bothersome. There's also an overlap of IBS and other disorders of gut-brain interaction. Moving away from these "organic conditions" but looking at the overlap of IBS and functional dyspepsia or functional heartburn or other conditions, how does the presence of overlapping disorders affect symptom severity and quality of life? How do you treat these patients?
Simrén: This overlap — what we call the DGBI family, with conditions in different parts of the gastrointestinal tract or different regions of the gastrointestinal tract — has been studied more and more in recent years. We have learned that having a DGBI in several different regions is clearly associated with a more severe phenotype, more severe gastrointestinal symptoms, but also more severe nongastrointestinal symptoms; as well as more severe psychological distress, reduced quality of life, and also higher healthcare utilization. It predicts more severe disease phenotype, if you put it like that, and clearly affects the outcome for the patient. For us as doctors, these are more [complicated] patients.
Chang: Yes, they generally have more severe symptoms and they're going to use healthcare much more often. There's more healthcare utilization, more visits — not to just the gastroenterologist or primary care physician but to other specialists as well.
Simrén: And even more surgeries, which is interesting.
Chang: More surgeries, yes. Do you think that some of these surgeries may not need to have been done?
Simrén: That's what I think.
Chang: Are there certain types of patients who are more predisposed to having overlapping conditions? For example, women may be more likely to have it, or are there other factors that are involved?
Simrén: There is this overlap with psychological comorbidity and also having symptoms outside the gastrointestinal tract. It's not clearly related to females vs males. It's more clearly related to these other comorbid conditions outside of the gastrointestinal tract. That's more important than this overlap.
Chang: I'm thinking about the healthcare providers who are seeing these patients, and many times IBS is diagnosed not necessarily by the Rome criteria but just by knowing that they have recurrent abdominal pain, diarrhea, constipation. Now knowing that these patients may present with esophageal symptoms or upper abdominal symptoms, what do you feel is the best approach for healthcare providers when they're seeing these patients and trying to delineate what diagnosis they have and how they are going to treat these patients? What advice would you give?
Simrén: First of all, the clinical history is key, of course, to address the different symptoms and try to pinpoint which of these symptoms are the most bothersome for the patients. Sometimes there are symptoms that you should address more carefully when you treat patients, so a holistic approach is very important. Address symptoms outside the gastrointestinal tract and try to get insight into the entire clinical picture. You put all of this together when you decide on treatment options. If there are more targeted symptoms for the specific part of the GI tract, then you can use more targeted therapies. If you have a more generalized symptom pattern in different parts of the gastrointestinal tract, then you need to think more broadly. If you're thinking more about brain-gut interactions, maybe use treatment options such as neuromodulators and behavioral therapies to address the entire clinical picture.
Chang: That's a good point, because if they have symptoms of upper lower gut or esophageal symptoms, you can think about treatments that can hit all these targets. It's important to recognize when you're making the diagnosis that they don't just have IBS; they could have functional heartburn, for example, or functional dyspepsia. You can treat them with over-the-counter remedies also, along with these systemic-type treatments, whether they're behavioral or neuromodulators. It sounds like you believe that you need some centrally acting treatment when you're trying to treat multiple conditions.
Simrén: For most of the patients, that's the case. Of course, sometimes one or two symptoms really predominate the picture and then you can target that symptom. You need to tell the patient that you are giving this therapy for that symptom. You don't give the patient, let's say, a proton pump inhibitor if they think that the reflux symptoms are the worst. And if you're saying, "Hey, here is something for your symptoms," and then they think they should have everything solved, they will be dissatisfied.
Chang: That is such an important point. I spend a lot of time with patients, but they'll come back sometimes and say, "I thought this medication or this treatment was for this symptom." And I thought I had explained it well, but maybe I had not explained it well. It is really important to tell a patient why you're giving them a treatment, what the treatment is, and what symptom you're actually looking to improve, and the time frame. I think many times patients feel like these treatments should work pretty quickly and they don't, especially for behavioral therapy or for neuromodulators. They take a while.
Simrén: That's a very important point. For neuromodulators, it takes up to a month before you can actually feel something positive. What is also important is that the side effects of neuromodulators often kick in immediately. If you haven't told the patient that when you prescribe the medication, he or she will throw it away, of course, if they come home having side effects the first couple of days and no positive effects.
Chang: That's why often I'll use a lower dose, but I'll tell them I'm using a lower dose because I just want to make sure they tolerate it. But then we need to increase it to the usual dose to treat the symptoms, because a patient could think about getting off the medication or the treatment earlier because they're expecting to see a response. Realistic expectations are really important to review with the patient.
Chang: IBS can also coexist with nongastrointestinal conditions such as fibromyalgia, migraine headaches, and interstitial cystitis. What do you think the factors are that are contributing to these overlapping disorders, which are gastrointestinal tract but also outside of the GI tract?
Simrén: Here again, we're talking about interactions between what happens in the body and then what happens in our central nervous system (CNS). Factors such as central sensitization, abnormal CNS processing of signals, and neural signals from the body play a role here. We can call it brain-gut or brain-body interactions that are abnormal or failing these patients. There are also some genetic risk factors for this overlap between different, non-GI functional syndromes such as fibromyalgia, chronic fatigue syndrome, etc. There was, for instance, a Swedish study where they looked at genetic risk factors in fibromyalgia patients and demonstrated that there were some shared genetic risk factors with IBS and chronic fatigue syndrome. Again, we have a mixed pathophysiology with genes playing a role, upregulation of CNS processing of all the signals of this from the body, and an overlap with psychological comorbidities, which is also very common in these patients.
Chang: People often wonder which one comes first. Do you get IBS first and then it's followed by fibromyalgia and migraines, or [vice versa]? What is your review of the literature and your experience with this?
Simrén: I think it can be in both directions, and that's also the same for psychological factors and IBS. There are long-term follow-up studies looking at psychological factors and IBS. IBS can come first and then psychological factors and vice versa, supporting this bidirectional communication between the brain and the gut. When it comes to non-GI somatic comorbidities, the same holds true there. Fibromyalgia comes first sometimes and IBS comes first sometimes. It differs between patients and there is no clear pattern.
Chang: You mentioned psychological factors as playing an important role in these comorbidities. We'll also be talking to Laurie Keefer, who is a well-known GI health psychologist, about that. But I want to ask you this question: Many times you could be in a situation where you're thinking, Well, they have symptom-related psychological symptoms like anxiety, which is completely understandable if you have these unpredictable, hard-to-control symptoms; they could develop some of these worries or concerns. Do you think that treating the symptoms of the gastrointestinal symptoms will lower the psychological symptoms if they're driven by the gastrointestinal symptoms? Or do you think it's always important to treat the psychological symptoms at the same time or even sometimes first, depending on which one you think is really important? How do you approach that?
Simrén: This is a very good comment because sometimes you have a patient with, let's say, severe diarrhea and they get anxious because of it. Then it's sufficient to just treat their diarrhea, and maybe the psychological factors will heal from treating their diarrhea. You need to address not only central factors but also the peripheral factors and symptoms, because symptom-related anxiety or symptom-related fear is very important. Many times you can actually combine peripheral treatments with central treatments if that's needed as well.
Chang: That's a good point. Sometimes we have to personalize the approach depending on the patient. What are other general recommendations that you would advise in managing overlapping disorders in patients with IBS in clinical practice? Is there anything that we didn't talk about that you think is important to mention?
Simrén: I would like to mention again the holistic view and the need to not only focus on symptoms that fit with your specialty as a doctor. For us, it's to think about gastroenterology outside the GI tract and try to see the whole patient that we have in front of us. Ideally for patients with more severe symptoms, we should have an integrated care approach, where we collaborate with different healthcare providers, such as gastroenterologists, pain specialists, dietitians, behavioral therapists, etc. We need to work together, especially for patients with the most severe symptoms.
Chang: When I see a patient, for example a woman with lower abdominal symptoms, it is hard to determine what the comorbidity of a pelvic pain disorder is because there are a lot of pelvic pain disorders. That region is sometimes hard to differentiate in terms of a gastrointestinal condition vs a pelvic pain condition because there are so many of them. I often refer to a gynecologist that I work with who is a pelvic pain expert. Do you find that challenging?
Simrén: Sometimes it is very challenging to dissect these symptoms, and I share that view of collaborating with different specialties. And gynecologists are one of the specialties that I collaborate with, so that's a very good point.
Chang: In fact, the comorbidity often could just be what they call cross-sensitization of the visceral nerves, or the afferent nerves. In human studies they've shown that if you irritate one of the organs, like the bladder, you could have increased clonic motor activity or vice versa. There also could be a more localized shared overlap in the pelvic region.
Simrén: Yes, and then you can target that overreactivity with combined treatment — the newer modulators, for instance.
Chang: I want to close by asking you, what are the key messages regarding IBS and overlapping disorders that are good to convey to our audience, and what do you see for the future?
Simrén: I think the most important thing is recognizing that this overlap exists and you need to address it in taking your clinical history, and also in your therapeutic approach to the patient. We need to think holistically when we see these patients. For the future, what we need is more treatment trials focusing on multiple symptoms. All of the current treatment trials that we have are focusing on a very narrow symptom range and symptom pattern. We need treatment trials that focus on the more broad symptom coexistence, to see if we can treat these symptoms in different parts of the body with a common treatment option, and have support from randomized clinical trials with that.
Chang: I can see that that's important, but it's probably challenging.
Simrén: Challenging. But we need it.
Chang: We could potentially focus on one condition that's predominant but also ask about the other symptoms. That's the first step. We often don't ask about other symptoms outside the gastrointestinal tract, and that would be something to do. Well, thank you so much, Magnus. This was interesting information and very real in clinical practice. It's something we see all the time, particularly in patients with more moderate to severe symptoms. Today we had Dr Simrén discussing IBS and overlapping disorders — not just of the GI tract but also outside of the GI tract, like fibromyalgia and migraine headaches. It was wonderful to speak to Dr Simrén. Thank you so much for joining us. This is Dr Lin Chang for InDiscussion.
A Distinctive Profile of Family Genetic Risk Scores in a Swedish National Sample of Cases of Fibromyalgia, Irritable Bowel Syndrome, and Chronic Fatigue Syndrome Compared to Rheumatoid Arthritis and Major Depression
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Cite this: How Do You Treat IBS With Overlapping Disorders? - Medscape - Aug 17, 2023.