The Basics of Inflammatory Bowel Disease

In this episode of PodMD, consultant gastroenterologist and hepatologist Dr Gokul Tamilarasan will be discussing the topic of inflammatory bowel disease (IBD), including what IBD is, how a patient would typically present, the treatment options, when to refer and more.

  • Transcript
    Please note this is a machine generated transcription and may contain some errors.
    *As always, all in this PODMD podcast is intended for health professionals and the comments are of a general nature. Information given is not intended as specific medical advice pertaining to any given patient. If you have a clinical issue with one of your patients please seek appropriate advice from a colleague with expertise in the area.

    Today I’d like to welcome to the PodMD studio Dr Gokul Tamilarasan

    Dr Tamilarasan is a consultant gastroenterologist and hepatologist. He trained as a junior medical officer and physician trainee at Royal Prince Alfred Hospital (RPAH), before completing his Gastroenterology training at RPAH and Concord Repatriation General Hospital (CRGH). Gokul also has a keen interest in teaching and currently holds a Clinical Associate Lecturer title with the University of Sydney.

    Today, we’ll be discussing the topic of the basics of Inflammatory Bowel Disease.

    *We do hope you enjoy this podcast but please remember that the advice here is of a general nature and is not intended as specific advice about a given patient. The views and opinions expressed in this podcast are those of the doctor, not PodMD.
    If you do have a patient on whom you require specific advice, then please seek advice from a colleague with appropriate expertise in that area.

    Gokul, thanks for talking with us on Pod MD today.

    Gokul: Thank you for having me.

    Question 1
    The topic of today’s discussion is the basics of inflammatory bowel disease. To begin, can you please describe for our listeners what IBD is?

    Gokul: Absolutely so. Inflammatory bowel disease is a chronic idiopathic inflammatory disorder of the gastrointestinal tract, and it has a range of intestinal and extraintestinal manifestations. The umbrella term of of inflammatory bowel disease then gets divided into Crohn’s disease and ulcerative colitis. But this is fairly artificial subdivision, and there is a group of patients that can’t always be easily put into one bucket or the other, and these patients are said to have indeterminate colitis. And just speaking about UC and Crohn’s disease separately.

    Most GP’s I think would be familiar with the fact that ulcerated colitis tends to be limited to the large bowel and primarily confined to the mucosa, so it’s a more superficial disease, whereas on the on the other hand Crohn’s disease is a pan, intestinal or pan enteric condition that is transmural deep. Ulcers can cause fistulization disease or or stricturing disease and abscesses as well, so that’s the main differences between the two and they both generally tend to have a bimodal age of onset so you get a lot of patients diagnosed in their teens or twenties and then you also get a smaller peak of patients getting diagnosed sort of in their 50s and 60s.

    Question 2
    How would a patient with IBD typically present?

    Gokul: It’s very variable is probably the best summary for that question, but the symptoms really depend on whether the patient has Crohn’s disease or ulcerated colitis. An really also depends on heir disease duration at duration. Sorry, but the typical symptoms would include some of either bloody diarrhoea or watery diarrhoea with mucus. Nocturnal diarrhoea is always pathological and needs investigation. Rectal symptoms in patients that have either perianal disease or proctitis could include rectal bleeding, tenesmus, or urgency, occasionally leading to faecal incontinence.

    And then more vague symptoms, which could be any number of diagnosis. But warrants further investigation would include abdominal pain or an abdominal mass fever or systemic symptoms mouth ulcers. And then fiscal officially, particularly around the anus or perianal abscesses, can also be a diagnostic feature of Crohn’s disease. And then finally the non intestinal or what we call extraintestinal manifestations can include things like inflammatory arthritism, pyoderma gangrenosum or erythema nodosam or ocular manifestations. So these, these are all a you know, a broad range of symptoms that don’t always present, but can be diagnostic of inflammatory bowel disease and need to be looked into, particularly if the less common ones are what you’re seeing for the first time.

    Question 3
    What is the diagnostic work up for IBD?

    Gokul: So I think like any presentation we generally start with simple tests and work our way up to the more sort of diagnostic or more invasive tests. So I think the basics in terms of what needs to be done at a GP level. I’d suggest that basic blood work and stool tests are probably the mainstay. This would include the routine you know, full blood count and looking for anaemia and raised inflammatory markers so raised white cell count CR, P or ESR are particularly common in Crohn’s disease. They can occur definitely in ulcerative colitis as well, but you shouldn’t be completely surprised if these markers are closer to normal because the fact is that given ulcerative colitis is confined to the boundary koser alone. You don’t always get systemic inflammation, which means that you don’t always get that reflected in your blood tests. We mentioned anaemia, anaemia of chronic disease can present quite commonly or even iron deficiency. Anaemia can be at the first sign of inflammatory bowel disease, particularly if you have small bowel disease, impairing iron absorption.

    We do need to exclude other diagnosis, so things like celiac disease needs to be excluded, so sending off a celiac serologies really helpful and relevant, particularly if the patient has comorbid thyroid disease, diabetes, or iron deficiency. Basic stool tests that are helpful in diagnosis would include excluding infective causes, so microscopy culture and sensitivity over cysts and parasite screen, or it would be very relevant as well as excluding Clostridium difficile, particularly in those patients that have had recent antibiotic exposures. The other test that has just made it onto the PBS late last year is the faecal Calprotectin. This is a really excellent test to essentially rule out any functional causes for intestinal symptoms, because if it’s a normal result the faecal calprotectin basically tells you that at that point in time there’s no active intestinal inflammation occurring and you can start to think about more functional causes such as irritable bowel syndrome for example.

    And the only other tests that might be helpful at the general practice setting might be a simple abdominal X ray, but I don’t usually advocate for abdominal X rays for every presentation, because a lot of the features on X rays aren’t always very obvious, particularly in subtle disease and. And patients that do have a diagnosis of inflammatory bowel disease will end up having a lot of radiology if we get X rays for every time that they come in. So we do try to minimise their radiation exposure wherever possible. And then the other tests which start to become a bit more specialised would include MRI scans, CT scans, intestinal ultrasounds and then endoscopic assessments such as gastroscopy and colonoscopy which all generally would warrant specialist referral and review.

    Question 4
    What are the treatment options?

    Gokul: I mean, this is a really broad question, so I’ll keep it summarised and keep it focused on what GPS really need to know about. I think the treatment options are improving all the time. 20-30 years ago the options might have been, you know, Mesalazine Psy appearing such as azathioprine or steroids. But you know, since the turn of the century, we’ve sort of seen the rise of the anti TNF medication such as infliximab or adalimumab, and then a whole plethora of other biologics, such as vedolizumab, ustekinumab. In small molecule agents, including tofacitinib, which is just come on to the PBS for ulcerated colitis this year. So sticking to the milder end of the disease spectrum.

    5 ASA drugs are really, really great drugs for mild to moderate ulcerated colitis and work really well usually in combination of both an oral 5 ASA and a rectal ASA. So that could include either an enema or suppository. Usually for left sided ulcerated colitis we recommend enema therapy as it’s probably the most efficacious in terms of reaching where the medication needs to get to the most effectively. Commonly we will also add in oral therapy because dual therapy has been shown to be to have an additive benefit, but we try and workout What is the most effective strategy and try and keep them on monotherapy if at all possible.

    Beyond the splenic flexure, so if you have diseases involving the ascending colon, the transverse colon enemas have a bit less of a role, and you start looking at more of the oral therapies in the rectum for ulcerated colitis We generally use suppositories because enemies tend to go above the rectum and not coat the rectum as well as a Suppository might.

    Sticking with 5-ASAs, these are not that useful in Crohn’s disease, and their use is not really at all supported by the literature, so I tend to avoid 5-ASAs in Crohn’s disease. The only exemption to that might be really mild Crohn’s disease, where you’re not Really reaching the benchmark to step up to thiopurines in which case you may use five ASA therapies. Spit, particularly ones that have Ailill release, such as Pentasa, but again the evidence to support this is very limited and in effect. Budesonide might have a better role in these patients anyway, and then there’s the next step up.

    The immunomodulators and immunomodulators include azathioprine, mercaptopurine or methotrexate and these are typically the next step in the algorithm for either Crohn’s disease an, and or ulcerated colitis. They have good evidence for both. And these should really be initiated in liaison with the gastroenterologist, but they can easily be monitored and maintained once the patient is in remission by the General practitioner and will talk a bit more about what role the GP plays in monitoring these patients

    Question 5
    What role does the GP play in the treatment of the condition?

    Gokul: So just following on from that last point. I think the main role GP’s play would be Assessing patients that are presenting for the first time and having a degree of suspicion as to which patients need further investigation in which patients may simply just need reassurance that they have you know, irritable bowel syndrome or some other non Or less concerning pathology.

    And then I think the other role that JPS plays monitoring diagnosed patients, particularly those patients who are biologic naive and are on the mild end of the spectrum in terms of therapy such as 5 ASAs or thiopurine therapy, some GPS just really need to be aware of. What to lookout for? How to monitor these kinds of patients? So starting with 5 ASAs that the side effect profile is fairly minor and usually patients tolerate these drugs really well, but occasionally patients can experience a rebound of worsening diarrhoea very rarely, but there are case reports report, you know, suggesting that acute kidney injury or pericarditis has been reported with these drugs and one thing to be aware of in the young male population is that reversible azoospermia so Essentially, irreversible infertility is a known side effect from these medications.

    The slightly bigger class of drug that page that patients need, slightly tighter monitoring for other thiopurines. So for azathioprine and Mercaptopurine the side is that profile Again, these are fairly safe drugs, but they do need close monitoring, so the side effect profile in the first sort of three month period can include abdominal pain, flu like illnesses, myalgias and not every patient will experience these, but it’s important to know that this can be very normal. And often wears off after about four to six weeks’ time if patients can get through that period.

    One tip that I have for GPS is splitting the dose so instead of taking say 100 milligrammes of azathioprine in the morning, if patients take 50 milligrammes BD, that actually can help patients because it allows the body’s enzymes to metabolise the drug a little slower and avoids overwhelming the enzymes to result in these side effects. The other side effect from azathioprine, Mercaptopurine is pancreatitis. This is pretty rare, occurs about 3% of the time, but it’s a sign that these patients really should not be on these therapies and there’s no way of sort of jollying them along splitting the dose, reducing the dose, and that kind of thing. You just need to take them off the drug and find something else to do Use. and then the other things to look for in blood tests Leukopenia so patients can get a leukopenia or neutropenia, and LFT arrangements are somewhat common but very reversible.

    So really, these patients should be having blood tests every three months. Um patients, another category of drug that GPS will see quite commonly and be pretty well versed in, so I won’t dwell on it will be methotrexate. So just to reinforce the messaging around lung fibrosis potentially, as well as hepatic injury and to avoid this drug in young female patients particularly but also young male patients who are planning to have a family soon. GP’s will also be pretty well versed in the side effects of long term steroid use. And I’ll just make a point here to say that IBD is not a condition where we expect patients to be on Steroids long term, even low doses of five or seven or ten milligrammes. That’s not something we aim for with the amount of drugs available. Patients should really be weaned off steroids completely And that’s something that needs to be Discussed with the gastroenterologist if a patient has come to you and said, oh, I’ve been on you know 7 or 10 milligrams of Prednisone for IBD my whole life, that’s quite concerning and really we should be looking at ways to improve that situation.

    Question 6
    What is the likelihood of recurrence of the condition?

    Gokul: So the natural disease course of Crohn’s and an ultra colitis is typically one of relapse episodes and then remission periods and the goal is to get patients into remission as quickly as possible and for as long as possible.

    We know from Crohn’s disease data, overtime, repeated episodes of inflammation and flare leads to worsening and progressive structural damage, and this can lead to worsening Quality of life’s increasing hospitalisation costs surgical therapy. You know an just worsening disease progression overtime so we really need to try and prevent recurrence as much as possible and then treat it as quickly and aggressively as possible. If it does occur. GPS are often the first port of call for patients who are flaring, so it’s really important to remember That whilst you will see flairs quite commonly that you do still need to exclude other causes, so going through your other differentials like we talked about earlier is still really important But patients are pretty good at knowing when they’re actually flaring versus having something a little different, so I think these patients do need to be reassessed Potentially MRI or colonoscopy.

    To work out how severe the flare is and make decisions about whether you know. Time has sort of run its course with the current therapy, and they need switching to another therapy and therapy has really changed in the last 10 or 20 years such that. We don’t try to dwell on therapies, you know. Too long we do really want to get the most out of each drug, but we don’t want to essentially flog a dead horse If patients are starting to get worsening aggressive disease, so we really need to be aware of the balance between you know, not burning through too many drugs, but also not letting the disease progress and get away from us before switching therapy. So that’s quite a fine balance. An patients that are flaring frequently more than once or twice a year really need really prompt reassessment and consideration of switching therapies.

    Question 7
    When should a GP refer?

    Gokul: So I think we covered a lot of when patients should be referred, so I’ll just raise some of the red flags and this is. These are common red flags for most gastrointestinal conditions. I think essentially iron deficiency anaemia, unintentional weight loss, or unexpected weight loss, rectal bleeding, or bloody diarrhoea, nocturnal symptoms or bowel movements are always abnormal & need referral set assembly history of bell cancer and signs or symptoms suggestive of Bell junction or impending bowel obstruction All need urgent referral and then other reasons for referral in the absence of red flags would probably include raised inflammatory markers without an alternative, ’cause that’s a pretty obvious one. And then a raised faecal calprotectin.

    So, just briefly, on calprotectin levels, the normal level or the reference range is is anything below 50. Then there’s a bit of a grey zone between 50 to 100, and these patients really could have a repeat calprotectin in two weeks time and that’s what the PBS criteria would suggest, is that any patients under 50 years old with symptoms that have persisted more than six weeks suggestive of inflammatory or functional bowel disease can have an initial calprotectin under the PBS and then at a repeat, calprotectin can be ordered in that Gray zone of 50 to 100. And sometimes these patients may have had temporary inflammation from perhaps a gastroenteritis episode or even have some perianal pathologies such as hemorrhoids which may give them an elevated calprotectin.

    But they don’t have any long-term pathology needing further intervention, so a repeat test may have dropped below 50, in which case they’re they’re better off being managed as a functional disorder on. On the other hand, if you have someone that has a calprotectin well above 100 or certainly if it’s above 150 to 200, then these patients would most likely have active inflammation and needs further investigation, likely with the colonoscopy, because even if they do backdrop back to normal, that level of inflammation is a little bit more concerning, and we’d want to follow that up, but that’s a rough framework for people that are Ordering calprotectins, which now thankfully can be initiated in the general practice setting.

    Question 8
    Have there been any developments in treatment in the last years or are there any in trials or development now?

    Gokul: There’s probably too many to name an outline for the purposes of this podcast, but and quite actually to be honest, the number of trials available is quite difficult to keep on top of, even for the general gastroenterologist, so I mean, that’s really good news for patients. It just means that there are lots and lots of different drug trials in the pipeline, and lots of available drugs becoming, you know, coming onto the market for patients with IBD, so it’s. Exciting time to be working in this field and we do have availabilities or options for patients to be enrolled in these trials in some of the tertiary centres across major cities in Australia. So I think that’s something that’s another reason for patients to be referred. If they’ve reached the end of their sort of treatment algorithm. Really look for other options, because trials can be a way forward for patients.

    Concluding Question
    Thank you for your time here today in the PodMD studio. To sum up for us, could you please identify the three key take home messages from today’s podcast on the basics of IBD?

    Gokul: Yeah, absolutely. So I think my main messaging would be one inflammatory inflammatory bowel disease. It’s really very common and should always be considered in the work up of any patient with diarrhoea, even if it’s non bloody diarrhoea.

    The second point is nocturnal diarrhoea or blood in the stool are never normal and they really warrant further investigation. Referral by to a gastroenterologist.

    And then thirdly, Prednisone is not a long term therapy for inflammatory bowel disease. It’s really best used as an agent to induce remission, but then you really want to aim for you know other steroid sparing agents to maintain that remission?

    Thanks for your time and the insights you’ve provided.

    Gokul: Thank you for having me

*As always, all in this PODMD podcast is intended for health professionals and the comments are of a general nature. Information given is not intended as specific medical advice pertaining to any given patient. If you have a clinical issue with one of your patients please seek appropriate advice from a colleague with expertise in the area.