In this update on inflammatory bowel disease, gastroenterologist Kendall Beck, MD, notes contributing causes, explains which tests have value, gives keys to distinguishing ulcerative colitis and Crohn’s (as well as the many conditions that mimic IBD), and delineates the benefits of early detection and aggressive intervention. Included is a rundown of pharmaceutical options, including biologic agents, with important notes regarding safety, along with general screening recommendations for IBD patients, who have a higher risk of numerous other conditions – from certain cancers to cardiovascular disease to depression.
sure thanks for having me. Um So my name is Kendall Beck. I am an assistant professor at U. C. S. F. And the G. I. Division and I'm the ambulatory medical director there and I also see patients at the SAn mateo clinic and you know I'm happy to talk to you about kind of IBD management and primary care today. This can be a very kind of open discussion. Hopefully hopefully folks have some questions and it can hopefully answer them. So let's see here have no financial disclosures um kind of give a quick overview of I. V. D. With epidemiology, ideology, thoughts on ideology. Anyway um diagnosis, current treatments and then we'll try to spend most of our time on general medicine um considerations in the IBD patient. First I thought it would just give an overview of the UCSF kind of colitis and Crohn's Disease Center. Um so that you can put faces to names if you do in fact send your patients to us. There's one doctor who's not pictured because she just recently started her name is chug. And so she will be seeing a lot of our IBD patients as well. Not everyone goes to the SAn mateo clinic. However um Dr Turtleman is our chief of our gastroenterology division. He he is not seeing patients at the SAN mateO clinics but he is uh you know sees patients from all over the area in California Dr Mahadevan is our director of the colitis and Chrome Center as well. And doctors. Elna chef Dr Lewin and Dr Rudra Patna. They are also in our IBD group. They neither of them goes to the peninsula to see patients, but they certainly also see patients from all over dr kota here. He's an MD PhD. He has an active research career but also sees um IBD patients. And he has a clinical focus in um really patients, young patients that are transitioning from the pediatric Gi world to the adult Gi world. So if you ever have any patients that are kind of just transitioning from pediatrics to G. I. And have IBD, he's our go to and um he does see patients within the SAn mateo clinic and then myself, I also see patients within our san mateo clinic. And so our physical address um is, you know, 1100 park place. You may already know this from referring patients there before. Um Like I said, just dr kota and myself see patients there. We have about between us two half days per month of IBD focused patient clinic. Um We can see uh follow up patients that are on the, you know, that live on the peninsula that don't have IBD. Um but are following up but all the new patients should really be IBD based if they're being referred to SAn mateo clinic that all being said right now, we're actually still doing all of our visits as virtual visits um for the SAn mateo clinic in particular. And so um you know, the experience would be the same for the patients at this point. So just kind of a quick overview of IBD itself. Um So there are greater than uh two million people in the country living with IBD. Um The the two most common forms of course are ulcer colitis on the left and disease on the right. We do have a certain small percentage of patients that we kind of consider indeterminate colitis. They may have features of both. Um but most of the time we're able to pin it down um with ulcer of colitis, it's mostly distributed through either just rectal involvement, prostatitis left sided disease, which is about 25%. And then the majority of our patients have pan colitis close to 50%. So involving the whole colon with Crohn's, we also like to denote the distribution with um whether patients have just really itis or I would actually say, you know, small bowel Crohn's disease And then whether they have small bell and colon involved, which is our most common, 45% and then colitis 32%. Um those that have only colitis of course with Crohn's, as you all might know already, uh the one of the major differences besides the fact that it involve anywhere in this in the intestinal gastrointestinal tract versus also colitis which only involves the colon uh patients also can develop fistulas and strictures and abscesses and that's due to the trans mural inflammation throughout the bowel. Um And so that is one of the other major differences between the two conditions, mm hmm. So we don't know. We still don't know exactly why patients develop IBD but the current hypothesis, you know, is of course that it's multifactorial and the diagnosis or the development of IBD exists when the right kind of genetic predisposition interacts with alterations in the immune system and environmental triggers. Um These environmental triggers may have something to do with factors with early childhood diet, early childhood infections or antibiotic exposures um which may alter the microbiome but but unfortunately don't have great causal links yet on any of these issues, we do know that uh smoking uh certainly um significantly increases the risk of developing of Crohn's disease. However, um we actually don't know for sure whether smoking whether smoking technically increases the risk for Crohn's or whether it's kind of a mitigating factor in that it actually can er sorry, excuse me, exacerbating factor in that it can exacerbate disease. And that's because um just if smoking was a causal factor, then it would not explain why some countries in the world that have the lowest incidence of smoking also have one of the higher incidences of IBD such as Canada and Sweden and the converse is also true that um many countries with a high rate of smoking have lowest rates of IBD. And so it's probably more likely that smoking is maybe not a causal factor but more modulating factor. Um We do know that uh smoking can increase the risk of kind of um more severe Crohn's disease at the very least or or developing postoperative recurrence or kind of minimizing the response to our medical therapies. There is data that shows that actually having had an appendectomy is protective for the development of all sort of colitis. Though I will say the relationship is less clear for Crohn's disease. Uh antibiotic use as I alluded to before has been implicated. There was there were some studies in the last couple of years that showed that greater than three dispensations of antibiotics in patients increased the risk of Crohn's and UC. And of course the broad spectrum, the broader the spectrum of antibiotic uh the higher the risk of developing IBD. There was also a recent study that showed that actually stat news. So patients who were on statins had a lower risk for heart disease. And then one thing just to note because this is kind of an old wives tale of it or or a theory from many years ago is that vaccines and ice right now are not associated with the IBD development. Whereas um you know many several of our patients have come to us asking about that. Unfortunately they're all just causal studies and I'm sorry Associates association studies and not do not establish causal links. Um There have been other studies looking at diet particularly recently. This is becoming a hotter topic. Um at R. D. D. W. Conferences and in this study basically showed that um patients that had a higher consumption of sugar sweetened beverages had a somewhat increased risk um of disease, although it was not as statistically significant. In a separate study, they showed that a pro inflammatory diet, which is kind of defined as a diet that's high in red meat, refined grains and sugar sweetened beverages, did increase the risk of chronic disease by a bit, with a hazard ratio of 1.06-1.99 but did not find a difference for you see in patients that uh took this type of diet. A separate study looked at this again and showed that artificially sweetened or natural juices um In terms, sorry, did not increase the risk for chrome's or all sort of colitis. However, um they did show that sugar sweetened beverages uh greater than one unit per day, did increase the hazards ratio of developing chrome or I guess developing IBD in general. However, this p value is not statistically significant, but when you broke it down into and you see, they again, saw this relationship of rosso patients, uh drinking beverages that are high that are highly sugar sweetened, um We're more likely to develop along the way. And that's shown here, this is patients who drink more than one drink away, sorry one drink a day um did increase the IBD risk, move on to talking about the diagnosis of IBD signs and symptoms are very similar between the two either can present with bloody diarrhea, 10 Asmus abdominal cramping and weight loss. Um In addition to extra intestinal manifestations such as UV itis, joint joint pains or inflammatory arthropod. These other conditions like skin conditions, marathi, Mendoza, german, gangrene, osa Crohn's disease may be more likely to have two for patients to experience weight loss. Um Along with it also, they are going to be more likely to have periodontal disease. Um and in Children, failure of normal growth can be the presenting sign of really either of these. It's important to always remember that there are ministers of IBD. So that includes infections, especially fungal infections. There's a chronic variable immune deficiency can also present with small bowel inflammation that can mimic Crohn's um. Other infections that kind of like the terminal ilium and sacrum area include tuberculosis, histoplasmosis, salmonella, rumah to logic disorder called the sheds disease can also look very similar and be tough to distinguish from Crohn's within the colon. Of course, other infections um can present similarly as well as diverticulitis or scan. So that's segmental colitis associated with diverticular assis, so that patients who have a little bit of inflammation uh kind of in the area of diverticular Asus and sometimes this can be hard to distinguish between that scan and IBD um patients that have cancer in our own immune checkpoint inhibitors, they can develop an IBD like phenomenon um within their intestine and on occasion we have seen patients who develop this and it's thought to be immune checkpoint inhibitor. And once the immune checkpoint inhibitor is withdrawn continue to have inflammation. And we actually end up diagnosing them with or you see occasionally colorectal cancer, ischemic colitis and Kaposi's sarcoma can mimic these diseases but hopefully should be distinguishable on biopsy. This is just a picture of scad where we see inflammation in areas of ticks. Um This is actually uh posey. This is a patient of mine who actually had Kaposi's sarcoma and we initially thought it was crones disease and lastly other conditions and said uh sarcoidosis is vasculitis, radiation entry empathy, lymphoma and amyloidosis. All of these have um can present like inflammatory bowel disease. And I've seen several of them. Um This is the end said. So this is the icy valve here in the sequel area and the colon and it's hard to probably distinguish with their little ulcers here. And this actually ended up being an NSAID antipathy rather than us. But especially because kind of like the terminal ilium and the icy valve area, we sometimes get confused. So what kind of testing are we doing for patients when they present with these symptoms. Of course colonoscopy is kind of the mainstay of diagnostic testing and I. V. D. All other tests are are even colonoscopy too. But all the tests are supportive of the diagnosis and not necessarily diagnostic. Those include crp fecal call protecting uh in capsule endoscopy which we typically reserve just in cases where we have not made the diagnosis based on colonoscopy yet. Um There was a 2015 systematic review that looked at the utility of CR PES are ethical cow protected to kind of distinguish between patients with I. V. S. I. V. D. And healthy controls. None of the biomarkers um distinguished between I. B. S. And healthy control. However uh they showed that patients had a less than 1% chance of having IBD if their crp was less than 10.5 or the production was less than 40. And so these are very good tests to help rule out IBD when patients present with kind of concerning symptoms like diarrhea, abdominal pain, that sort of thing. This is just a couple of pictures of inflammatory bowel disease. On colonoscopy. This is a you see patient, this is a corona patient with these deep linear ulcers. Um Most important thing is we like to document the severity of inflammation and the distribution where in the ballot it's located. And then what we're looking for on biopsy is a chronic active colitis or chronic active daily itis. Um really it's having both the chronic and the active inflammation that are that are key kind of for making a diagnosis Interestingly enough, we're all kind of taught that granulomas are found in disease and not you see. And that is true. However, I would say that we actually see granulomas pretty infrequently on biopsies. Even in our established patients, um probably 20% or less of them actually have granulomas on their biopsy. So I just want to talk a little bit about our our kind of goals in treatment. And um so what we're going for for patients for treating when we're treating their IBD. So one goal can be clinical response. Um And uh when patients have a clinical response and that just means that their symptoms improve, that can be associated of course with improved symptoms and improve quality of life if we're looking at clinical remission, meaning that symptoms are completely resolved, no symptoms that actually has shown to be associated with decreased hospitalizations. Um The and then the kind of the, I guess goal that we're all striving for is deep remission. And that means that they're endoscopy is normal, not just their symptoms are normal, but the endoscopy is normal and potentially even their biopsy is normal. And this has been shown to correlate with the avoidance of surgery and minimal to no disability for our patients. And so this is why this is really our goal for every patient is to reach a deep sustained remission and um so that we can do our best to avoid surgery and disability for our folks. How do we do this traditionally treatment styles kind of started with the mildest lowest risk medications. However, there is data to support that improve that there are improved outcomes with early aggressive treatment and achievement of remission early. The study showed that patients who went on biologics early had similar hospitalizations and er visits to those with actually just mild disease. And that the use of biologic was associated with declining resection rates for both you see. And crows and so are 2020 A. G. A. U. C. Guidelines suggest using biologic agents early rather than a gradual step up in therapy. So what are the clinical predictors of severe disease? Um And and subsequently patients that are at risk for surgery patients who are younger when they're diagnosed. Those that are non smokers at least for um You this is for you see actually uh disease duration. So having had the disease for a long time delay in treatment. So patients that achieved healing of their mucosa at one year after diagnosis had to five times lower risk of collecting me disease severity of course. So moderate to severe disease versus mild had a three times risk of collecting me. Having had a history of hospitalization And for sorry for you see particular having pan colitis. So having um all of their colon involved led to a 20-40% risk of collect me versus a 2 to 14% risk of collecting me if they only had left side disease with you see having deep ulcers, high C. R. P. S. And a history of Cd for C. M. V. Infection specifically for additionally having penetrating or structuring disease and periodontal disease. So the big the biggest ones though here are young age at diagnosis, pan colitis, deep ulcers, history of hospitalization and steroid dependence, high cRP s history of CD for CMB infection. And then for peri anal official izing disease. Those are the patients that are at highest risk of requiring surgery. Talk a little bit about our meds here. Um so broke these down. I'm actually just actually two fastest onset and and then we'll talk about the safest ones. So fastest onset is going to be the anti TNS. Um For the most part we do have multiple options. Uh summer ivy some are subcutaneous. We have the most data for these drugs because they've been around the longest. They do have high immunogenicity which means they are high risk for developing antibodies to these drugs that can neutralize the drug and make it ineffective but they are very good for systemic involvement. They are systemic immune suppressants and they're really good for other conditions associated with IBD skin conditions. Joint conditions sorts of things. There is a risk for infection. Very very low lymphoma risk but not zero and risk for skin cancers including melanoma. We have our some of our newer drugs that jak inhibitors. So janus kinase inhibitors. These are oral which is a huge benefit for our patients and not technically a biologic they're they're small molecules and they come in pill form. They have can have can have a rapid onset. We have seen patients respond as early as three days after starting. Um They're they're good for patients who have joint involvement but there are some safety concerns as well. There's increased risk of shingles, non melanoma, skin cancers and actually um thrombosis symbolic disease. In fact there's a black box warning for increased risk of thermal metabolic disease. Uh for older patients that are on a high dose of the jak inhibitor and also have a high risk of have cardiovascular risk factors. Basically both of these are basically essentially contraindicated in pregnancy. Um That we though we would want the patient to speak with us before stopping them if they became pregnant. Um On the bottom I've included the drugs that have the best safety profile. So our anti integration is vandalism. Um This is the I. V. Medication they are testing sub Q. That we did not update improved yet. Um This has the slowest sorry. Slowest onset of action up to six months. It might take to see an improvement in symptoms. Very low risk for developing antibodies. It is gut selective which means it's not um suppressing the immune system's systemically. It's it's acting at the level of the gut and therefore has a very good safety profile. But it's not great for patients that have other extra intestinal conditions. Mhm. And then lastly we have been risen which is approved for only um These drugs are both given with an ivy induction dozing and then they're given subcutaneous lee. They do probably have a little slower onset than anti TNF but maybe don't take as long as brutalism. Am they have been shown to be better for anti tina failure patients versus vandalism. Um They have low risk for developing antibodies and have a good safety profile and they work really well with the skin. They're they're really good. For example, psoriasis medications. And so these are good for skin involvement. It was kind of a summary of um I call this our safety pyramid of IBD medications. I think the most important thing to realize is that the least safe thing is inadequate treatment let patients keep kind of languishing away with their IBD. So we do our best to get patients on the most adequate treatment for them. I would say that systemic corticosteroids are again the uh have have a high risk for safety concerns. Um Our thigh appearing drugs plus our anti TNF combos are probably the next least safe and that's mostly due to the thigh appearing next would be appearing to and sofa, sofa sitting. Um Then our anti TNF is alone and then our safest drugs I would consider brutalism is to kind of Okay, so I just want to spend a little bit of time going through some of the data on primary care or general medicine issues for IBD patients. Uh Several studies have shown that patients with IBD actually may receive less preventive health services than general primary care patients. And part of that may be because many IBD patients actually do not have a primary care doctor. Uh they tend to be younger and often do not have co morbidity illnesses and often just see their gastro neurologist as their only physician and often don't understand why we're asking them to see a primary care doctor as well. Um So it's it's really crucial to clarify with the patient the limits of specialist care and also when they do have a primary care doctor to communicate their needs to the primary care clinician more specifically, patients with IBD haven't shown to be under vaccinated in several studies. Um They are at an increased risk for flu pneumococcal pneumonia shingles. Um In this one study of 169 patients, 86% reported current or past immuno suppression use, only 28% received regular flu shots, 28% had had to have the vaccine and almost half basically cited just a lack of awareness of needing these vaccines um and being at high risk as the most common reason they did not receive. So what are our vaccine recommendations recommendations? Um all IBD patients, patients, sorry, should receive non live vaccines that are in accordance with national published guidelines. Some exceptions would be for kind of earlier vaccines. So for patients that are immuno suppressed, they should get the Numa Vax um or pneumococcal vaccinations at any time when they're immuno suppressed and the shingles vaccine we usually recommend at age 50 or older or if they're on top a synonym or sell jams, this is not necessarily a formal recommendation, but it's kind of expert consensus. Live vaccines are contraindicated in patients that are on immuno suppression and that includes any of these drugs. Anti TNF sticking. Um averse to laura, predniSONE greater than 20 mg a day. Uh Six more capture, appearing greater than this dose and then methotrexate as well um at a higher dose. And we would want to wait three months after stopping those drugs before giving a live vaccine. One exception is there is a version of the monkey pox vaccine that's technically live but it's considered non replicating. And that one is okay, we've talked to our infectious disease doctors about that. There's no increased risk of flares with vaccines and um any potential for kind of a reduced response to the vaccine should not discourage vaccination. Um if a patient is not yet immuno suppressed but will be soon. Um then we do encourage vaccinating before immuno suppression if possible. So what cancers are patients at high risk for that have IBD. So colon cancer of course um patients are at high risk for colon cancer and we do screen with colonoscopy every 1 to 2 years after they've had a colonic disease for eight years. The one exception is or one of the exceptions is that we screen immediately. Um not waiting eight years for patients that are as soon as they're diagnosed with concomitant PSC. And they get a colonoscopy every year strictly um annually because the risk for colon cancer is much higher. In this group, patients are at higher risk for skin cancers as well. Non melanoma, skin cancers are increased with Kyprianou's melanoma may be increased with anti tina. And there have been some studies that showed a slight increased risk in melanoma in all IBD patients, regardless of anti tina use. And so we always recommend our patients see a dermatologist once a year for skin checks and of course use sunscreen. Um, IBD patients are at a maybe at a higher risk of cervical cancer and there is data that suggests that they patients are immuno suppressed, might actually be getting screamed less less frequently for cervical cancer. And so we recommend that those that are immuno suppressed, especially if they're on a thigh appearing because that does seem to increase the risk of cervical cancer that they get an annual pass. Some patients or many of our patients ask about osteoporosis. There is a high rate of osteoporosis in the IBD population um probably significantly contributed by, you know, past steroid use having chronic inflammation, possibly low body mass index. And of course patients that are smoking. We generally recommend exa for kind of national guidelines and then also in patients with particular risk factors. So men that are have IBD and greater than 70 postmenopausal. Women with IBD at age 65. And all all patients that have risk factors including prolonged steroid use history of a low trauma fracture and consider it in chronic smokers. I think this would be this is probably obvious, but we do of course encourage tobacco cessation. Um as I mentioned before, active smoking is a risk factor for more severe crones and reduces response to medications um and may increase to sorry, may contribute to an increased risk of blood clots, which they already are at risk for. Um We do recognize that active smoking has been shown to actually benefit, you see, but of course we don't recommend it. We still believe patients should um be canceled to quit. And offered medical therapy to do so if needed. Um Our patients with IBD have increased risk of cardiovascular disease. They are, there was a large retrospective review in the last few years that showed heart attack was higher in IBD patients as well as heart failure. It actually showed that getting getting therapy with biologic. So, being on therapy for the IBD reduced the cardiovascular incidence rate in this population. So by hazard ratio of .7 and that being on steroids was associated with increased overall mortality over an anti TNF drug. And so um cardiovascular disease and hip fracture work contributed most to this. Increased mortality in patients on steroids. So just another reason we want to get our patients off steroids. Similarly patients are at higher risk of stroke as well. The risk of stroke was uh 3% in our crones disease with the odds are issue of 1.54 and 3.4% in you see with an odds ratio of 1.7 as compared to patients with no IBD. And similarly to cardiovascular disease being on an anti TNF reduced the risk .53 odds ratio in .44 of having a stroke. So treating the inflammation, reduced the risk of cardiovascular and cerebrovascular complications. And just to note, we get this question a lot too. Using a daily aspirin did not impact the clinical outcomes in IBD population in the sense that it did not worsen IBD or cause IBD flares. And so we are strongly, we strongly encourage daily aspirin use for patients that are at high risk for um vascular problems, something that's becoming uh the hotter topic. And then people are becoming interested in researching now is the risk for non alcoholic fatty liver disease. And the IBD population um that we do have data that shows that nah field is higher or sorry, more common in the IBD population. Uh And so the blue they're light blue is the general population and it's actually the highest in cartoons versus you see this is snaffled in general. This is actual nash. So actual Seattle hepatitis numbers are small but still a little bit higher and this is um related cirrhosis. So risk factors for nah filled in. And IBD population include older age, higher B. M. I. Longer disease duration. And actually those who have a history of surgical resection had a higher risk for an apple, which is interesting last two slides. Uh So patients with IBD do have higher rates of anxiety and depression. They may have um this and this is associated with increased bowel symptoms, clinical recurrence of IBD, poor response to medical therapy of IBD, poor quality of life and reduced social support. Um there was a study that showed that increased depression, there was increased depression, anxiety and patients had a crp greater than five And that um there was in patients with an active site co morbidity and IBD that resulted in 10 excess clinic visits and 3.1 excess hospital days per year. Early recognition and treatment can improve a patient's quality of life. And so we recommend that all IBD patients should be screened and treated for depression, anxiety. And the last thing uh fatigue is another factor that's quite prominent in our IBD patients. This european city looked at fatigue and its association with work productivity loss of 1500 almost 1600 patients that were surveyed. Uh It's about 780 returns their surveys, 53 or half of the patients reported some degree of work productivity loss and fatigue here at the top. This was the most common um symptoms cited as work productivity loss. Um Other conditions that kind of predicted fatigue included patients that also had our theologies and active inflammation. So, our recommendations for IBD patients that that kind of complain of fatigue are to screen for nutritional deficiencies. Iron panels, B 12 vitamin D. Often I'll add like a zinc as well, screened for thyroid disorders, screen for sleep disorders and a mental health screen as well. And then our kind of recommendations for treatment if all of these things kind of come out normal is graded exercise program, improving sleep hygiene, um kind of mental health interventions like cognitive behavioral apps, those sort of things. This is our summary. Just that I? Ve patients do have important general health care needs. We kind of expect the gastroenterologist to perform of course appropriate laboratory TB testing for their biologic drugs perform the colon cancer surveillance. They perform drug monitoring. But at least at UCSF, we really encourage patients and their PCP to work on vaccines, tobacco cessation, other screenings and other cancers and depression anxiety. You can find health care maintenance checklist for your IBD patients at the core of the colitis Foundation website. So thank you and happy to ask any or sorry, answer any questions anybody had
