During this 20-25 minute pre-recorded lecture, Dr. Louis J. Cohen discusses the topic of extraintestinal manifestations. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards. this section of the board review course will focus on extra intestinal manifestations and inflammatory bowel disease. Extra intestinal manifestations come in a lot of forms for each one that we go through will focus on key points that will be picked up on the board specifically the epidemiology of that extra test manifestation, the clinical manifestations of it and what are the general treatment paradigms? And we'll focus on the three major groups of extra intestinal manifestations that again, are typically covered, which are those involving the joints, the skin guys, so to provide a little overview, uh huh. We think it would expand to some manifestations obviously think about the skin, the joint in the eyes of being some problem. But in IBD you could argue that affects almost any word, right? And we see associations with a variety of diseases sclerosis, to thyroid itis, to autoimmune hepatitis. And you know when we think about this and to sort of just transport Gross for a 2nd. Um the reality is they come from the fact that inflammatory bowel disease is probably a heterogeneous group of diseases. And what we see here from a seminal paper published nature in 2012 is that there's a lot of overlap between inflammatory bowel disease as well, as well as other immune diseases. I'm including primary immune deficiencies. Um and it leads to this idea that you can have the correlation between IBD and other immune diseases and the question always becomes, is it a causation? Right. Does having IBD actually cause of these diseases? Or are they just part of a larger overlap syndrome. So, again, this and itself will not be covered on the boards. But I do think it's an important way to start to conceptualize why we see so many associations between IBD in other immune diseases. So again, to bring things back in Now for today's presentation and again, for the purpose of the board review, we're going to focus on the extra intestinal manifestations that affect the skin, the eyes and the joints specifically you? Ve itus spondylitis, arthritis, piau derma and everything person. So, in terms of all comers for extra tesla manifestations, 50% of IBD patients will experience at least one extra intestinal manifestations over the course of their disease. The number of patients increases over time in terms of time from diagnosis and once a patient has diagnosed the single extra intestinal manifestations, much more likely to get a diagnosis of a second. Extra intestinal manifestations are more common in Krems, specifically in chronic Crohn's disease and most gender equal. So this is actually important point from a border review because there's some that are not generally specifically movie this is more right and close in spondylitis and primary sclerosing cholangitis who more common in men. And what's interesting is that these are also the extra intestinal manifestations that don't associate with disease activity, says another boarder viewpoint, which we'll get to as we get to some of the individual extra intestinal manifestations but understanding which ones are going to parallel the disease course and which ones don't um is a frequent question and it's easy to remember because the ones that don't again, uveitis and close in spondylitis and PSC are also the ones that are not gender equal. So when we think again in general, the important concepts and diagnosis person foremost, you want to search for associated immune diseases. The second thing is the timing of the disease activity which we just touched upon. So there'll always be an important clue such as patient begins have onset of ballots symptoms and then it's followed by joint or something to that effect. Another important thing is you're getting you're working with the questions reviewing the medication history because oftentimes medications and themselves can be associated with these problems. It's not necessarily the inflammatory bowel disease such as anti TNF. We can see being associated with psoriasis arthritis, judges in some patients we questioned associations with vascular it's politis, skin and joint manifestations are associated with smoking. Again, this may be a clue that's provided in the question base. Other things to remember in Tv or vandalism app can treat extra intestinal manifestations that treats the ones that are related to the disease activity. There's also some reports extra intestinal manifestations can actually develop on interview, leading some people to sort of hypothesize that has to do with specificity and trivia to get harming my lymphocytes again, this is something that's still being worked out. Another important thing to remember is that the treatment of these extra intestinal manifestations will often focus on multidisciplinary teams, but an important thing report of you stand point is knowing the warning signs. That should lead you to say yes, we would refer the patient urgently. And for anybody interested in sort of reading more, I'd say the consensus statement from Echo is a fantastic resource to continue to brush up on that reference is provided below. So the first extra intestinal manifestation, which is one of the more common ones, but we'll get to is arthritis. So spawn below arthritis really is IBD associated. I'm arthritis and they can come in two forms come an axle or peripheral peripheral offer for axial and involves the n theses which I've highlighted here. I always joked that as a gastroenterologist, I seem to always need to brush up on all these old pictures that used to be second nature um other axial ones are secretly itis and enclosing spondylitis. The peripheral arthritis involves the joint. And the important thing to always remember is it's non destructive. So if they're leading you down a question line, when we talk about destruction of the joint, you should be thinking about something that is not a sponsor of right. It's not an IBD associated different this and peripheral arthritis and more common in crimes spawned. The lower arthritis is common to inflammatory bowel disease. However, also can be found in other diseases such as celiac disease, infectious colitis. We highlighted some the organism associated respond arthritis here Also we have Whipple's disease post gastric five passing Bichette's. So again think about other immune diseases or other diseases that may be in question line and it may not be always IBD as an answer. 70% of patients respond to arthritis has subclinical intestinal information. So this is an interesting thing from a practice standpoint which is that if a patient presents to you with a nondestructive arthritis suggests of its pondel arthritis And you look endoscopic Lee in these patients even if they feel well 70% of them will have an increase information and what are the mechanisms. Well certainly there's a genetic risk H. L. A. Between seven is something we always think about as being highly associated and close in spondylitis. An important thing to remember is that it's a little bit less associated in the I. V. D. Associated aren't being close in spondylitis. So it's not 100% diagnostic right? If they're actually be 27 negative it doesn't mean they can't have ankle isn't spondylitis especially in and again if we look at and close in spondylitis jeans. eight of the 11 ones that have been identified are also shared as risk close eye for the development Bowel disease highlighting what we sort of put up for. From that seminal nature paper that there's a lot more overlap in these diseases and probably the way that we're going to think about extra intestinal manifestations. My suspicion is will change over time. People have also hypothesized about the microbiome. We think that pathogen episodes lead to sort of this idea of molecular mimicry, right? That you get a campylobacter infection in that brightest and people have links changes in the microbiome potentially through certain pathways familiar to be petrol physiology. So the development of extra intestinal manifestations and this is thought to occur primarily through homing of mucosa associated Lucas sites, which is also why we can see the fact that yes, mm the use of antibiotics can actually treat that. Yeah, I am again the ones that tend to track with the disease activity. So 6-46% of patients with VD will develop an arthritis against more common in choline disease and in patients who had other action test of manifestations and peripheral arthritis. As we discussed more right In 2016 systematic review, 13% of patients at a peripheral arthritis followed by secretly itis and then find my ankles and spotlights. So again, the most common type of vision to some manifestation from arthritis standpoint is peripheral arthritis. We talked about peripheral apparatus. We talk about Type one versus type two. Type one of the patients. I think we all think about it. This is an acute onset policy articular less than six joints. It often affects the bigger joints such as knees can be asymmetric. It happens often times early in the bowel disease and it correlates very well with flares patients. Players improved, they improve in terms of writers, this is the red hot junk Take two which is less common. This is chronic, it's polly articular, it tends to affect the metacarpal Flandreau joints. It can be migratory. Oftentimes it's symmetric and it does not correlate with the ivy flares. This is one that I have a feeling that with we'll see it as being part more of an overlap syndrome For the purpose of the boards. This is the Type two. So again, type one correlates well with disease activity. The red hot large joint. Type two does not correlate well with disease activity can persist is the smaller joints secretly. I this and spondylitis Oftentimes the answer is before 40. The question leading that you're always gonna have to pick up on is its pain or stiffness in the morning or after rest. It's relieved by exercise. These patients if they have limited flexion and reduce chest expansion. We have to think very quickly. But ankle is in Spagna lists. It's unrelated to the IBD activity and often patients can be asymptomatic but still have radiographic findings as we see here. And Tacitus is a little bit less common effects. About 2-4% of patients. It's most common in the planter and achilles and then the finger which we call dr lights now in terms of the diagnosis of arthritis. We think with laboratory findings usually the inflammatory markets reflect bowel disease. We do not see a positive rheumatoid factor. And we talked about h. l. a. b. 27 but I also wanted to make sure that again an I. V. D. Associated s. It's not always as high as it is not associated. Mhm. If you were sampled the synovial fluid of that red hot joint which is an important thing to do because we want to rule out an infection. You can see a polymorphic nuclear leukocyte predominance and if you did a biopsy of the synovial which would be helpful in our a it would be non specific here. The radiographic findings again we see soft tissue swelling, jokester articular author osteoarthritis. But you should not see joint erosions. They talk about destructive changes. As you see here think about rheumatoid psoriatic or osteoarthritis. This is not IBD associated arthritis for axel arthritis. Against the gold standard we think about the X rays. C narrowing sclerosis. The joint space ankle Asus again, fusion and this will increase the time will be symmetric. However MRI really is going to be the most sensitive thing and you can have a symptomatic patients that still have them re inflammation. Now those Only 1-10% will actually progress to a close and small so we can see sort of a sake really. Itis In 20% of patients that doesn't often mean that there. Yes so your differential when we see a monitor arthritis and give them more aspirin to relax septic arthritis. Everything we know. Dozing or cellulitis that occurs over the joint can seem as though it's an arthritis by the joint swells. But when you try to aspirate something, nothing a vascular necrosis, we always want to be thinking about. Especially in patients with a history of steroid use in hypertrophic officer of rob return arthritis is symmetric. There's no anthrocytes and it's destructive. We can often have infections such as line as well as other inflammatory diseases such as gout or for peripheral arthritis. The answers for treatment is always to control the IBD for type one. Again, the red hot sauce. Similar treatment strategies, we see a DVD that have overlapped with other sort of our type treatments include things like selfish fallacy, methotrexate six MP or anti TNF. Some patients that have both of these things, especially if they have a type to referee itis. We may try to reach for these sort of overlap therapies, things that might be different than we used to treat. For instance, rheumatoid arthritis. But we do not use an IBD do these things like N sets. So it is important to understand that our patients can tolerate these in the short term and set. You can a map which is actually associated with the development. Yeah, outcomes more often determined by BD symptoms for the treatment of enclosing spondylitis. It's again, similar to the treatment of the peripheral, it's important to remember the anti TNF medications may prevent the progression to and close in spondylitis from inflammatory arthritis. So those patients with IBD maybe having a symptomatic inflammation of your sacred joints on MRI may want to consider starting TNF and their outcomes here are independent of the IBD activity. Mr kinda mad mechanistic we should help those treatment for is a little unclear. So after this our brightest section will transition to a question Sort of question # one your patient with newly diagnosed Crohn's gets an MRI pelvis to evaluate official and it demonstrates sacred really itis the patient is asymptomatic. The next step is start with the truck seat, repeat the MRI in a year. Starting footsie map reassure the patient. The answer is started flexing that and flex man may decrease the progression and close in spondylitis is indicated for official. Izing Crohn's disease. You're choosing this because the patient has Crohn's and it has the added benefit having been shown to decrease the progression. So to the next section we'll discuss in disease. So skin disease is associated with IBD in 15% of cases. The most common one is actually psoriasis. So 10% of millions of these patients have psoriasis often as a plaque psoriasis and can proceed the IBD, it's independent of the IBD activity. So again, when we think about that nature article, you overlap genetically between IBD and Soraya is actually quite great. The important thing to remember is this is one where you want to also look at the question base and anti TNF associated psoriasis was something that if you start to see it effect. Again, it's a typical distribution are benefiting the palms and sort but when we don't always think about psoriasis because we usually think about that as a separate disease. So for the purpose of the overview today we're really going to focus on Hiroshima no does um and powder McCain growth. But it's also important remember other skin diseases that are associated such as melanoma and non melanoma. Skin cancers and hydro tonight is super TBA some rare ones. We think about the neutral Felix skin diseases such as Sweet syndrome. These are patients you want to think about who have tender popular or plaques on the head and neck. Again, always be square. Itis. The fever is an important one and its associated active. IBD is exquisitely steroid responsible. There's also this aseptic abscess syndrome and now we're sort of in this weird territory where we see screen created skin abscesses, the neutrophils predominance relapsing was also bowel associated Potosi's arthritis proceeds. The skinner disruptions with postural and vesicles on the upper string here. We also see this idea of metastatic Crohn's disease. We have ulcer modules with granulomas, um patients, these are again very rare uncommon ones you're unlikely to see on the board. With the exception of taps Sweet syndrome. So focusing now in common ones, like everything, you know Dawson again, following our protocol, the epidemiology, you know, Dawson is associated with a wide variety of conditions beyond IBD. We can see it infections can see in patients on certain drugs such as over contraceptives, patients of pregnancy or there's malignancy. How often is a idiopathic The IBD associated for 7% of patients and the diagnosis for everything, you know, Dawson is essentially right that correlates with the IBD activity. They're tender, non ulcerated fixed modules, neuroscientists. Often they hit the shins or the equals thighs. They developed very rapidly and can have a program with fevers and anthropologists. Now, if you didn't feel comfortable with the diagnosis clinical, you could biopsy in general, we don't do this outside unless there is a typical distribution such as affecting the hands of face. And if you did it, you would see a particular virus which is initially in the pacific but then later Granules with neutrophils and you can sometimes have real it is you have to think about a differential diagnosis. Again, we talked about the fact that everything, you know, Dawson can be associated with other diseases and I would do this but persists greater than eight weeks. It's not involving the legs or there's ulceration and that can mean instead of Dawson which are actually looking at is either a vasculitis infection, malignancy or we see it in other conditions. Again, we have to think about other associated diseases. The treatment for everything. When Madison is usually itself resolves. You also want to treat the IBD. sometimes in patients we can use insets protesting i that has been looked at capstone or culture scene. Um but in general, the answer for the boards is usually treated. Pyro dermarr, gangrene, awesome. This is much more rare. Um let's see about 3 to 10 million. 3 to 10 per million. It often again affects women. So the gender distribution is not the same. It affects all the patients. 50% of patients who have power dark. No, it's from having associated disorder. So just like earthy megadose. Um, it's not always guaranteed that they have IBD but oftentimes they do 41% of patients with tara dermott do have IBD. We can also see it in patients who have arthritis malignancies or certain disorders. 2% of all sort of fighters patients, which is those higher than chronic disease. You can receive the IBD and again, it's not gender similar. So therefore it also doesn't parallel the course. There can be a genetic defect. So, we actually see in some patients with para derma they have genetic disorders and we think that these things may affect nutritional function. You also have a systemic information. Clinical manifestations of power. Derma has inflammatory capital not to our physical forms an ulcer. These are painful. Um, ambitions can often have fevers as well. Pathogen is documented 15- 30% of patients. So that is that these lesions occur at sites of skin trump. And if you were to send a patient to the operating room, the risk of them getting married. Irma at the operating site usually increases if they have hired Irma already at that the clinical manifestations. So all sort of kind of the classic when we think about it's often on the lower extremities and the expense peripherally in degenerates central. This is the violation edge that then becomes necrotic and patients and multiple lesions postural er tends to be the one that's the most associated with IBD. It's associated with the activity as opposed to the whole sort of the classic one. It develops very quickly in patients kind of fevers and anthropologists and I can also be on the oral mucosa. Then the more atypical ones such as bullets which can be offering more seen neurologic diseases vegetative. You get these sort of painful plaques and varicose lesions but often neck. Um and then they would lead us the diagnosis. So in this case for pyro derma, the biopsy of the ulcer edge can be helpful. Sometimes we can diagnose it clinically just based on how it looks and obviously being associated with certain conditions if you buy and see it into neutral filic biopsy so early is peri follicular information and you have internal abscesses and later on it can progress to frank necrosis. Mixed infiltrate as well as the pacific beside a plastic mask. Often paradigm was misdiagnosed and this can lead to problems. So a biopsy for the purpose of diagnosis and in itself is not going to cause significant issues but we do run into problems when people think this is actually wounded infection and so they begin to aggressively to breed it and then I can lead to much worsening of the road. Irma. Do too much worsening skin damp. Right? So this this path of consistent the differential when you see these you can think of a vascular inclusion, anti false Philip it in a stasis wagoners, infections, injury. And again we talked right treatment. Usually these delusions can prove very quickly it can take months for total. You want to avoid trauma again so you don't want to be reading these things be it's also think about the dressing changes. We just have a few superficial ulcers. Your treatment maybe just local corticosteroid, calcium inhibitors. The more extensive power derma. We think about it the same way we think about treating I? Ve right there's an induction phase you can use glucocorticoids or cyclosporin and then there's a maintenance phase we can use finally is tired Park city more recently though we've started to lean on inflicts map. We see good response rates and can be used both for induction activity again doesn't always really d and the outcomes are the same whether or not a patient has IBD with 50% healing although patients can develop scars and often times these can re occur. So now question #2 from the skin section, your patient has longstanding all sort of politis. Intermission on Adeline. The patient was recently campaign and presents your office with a painful lesion. Which of the following findings is most likely to accompany his pathologic diagnosis. Spira Keats, gram positive cox and clusters a lymphocytic particular itis or neutral filic inflammation with intradermal absence. The answer is the this is early piau derma. The lymphocytic colitis would be earthy menudo awesome which is not consistent with how the solution looks. So. And for the final section we'll talk about eye diseases and if you have to sort of review things when it comes to the joints for the eyes basically fairly hopeless in store for every board review. I have to go through the slide again a familiar I was myself, the Stelara, the anterior chamber where we call you via and this something starts to help you think about the problems. That's the most common one we see is that the school iritis to in effect to the 5% of patients you be at. This is the other one with the interior chamber common and this is where you can see where is the intermediary the posterior chamber we may not see. And so you have to have I'm a high clinical suspicion. The uncommon ones that happened in IBD are slower iritis vasculitis of the I. R. Keratitis. You should also be thinking about medications here just like psoriasis. Garentina associated just like a joint problems. We can have osteonecrosis, secondary of steroids. Sarah's here can also lead to sort of mimicking and patients can have block right clinical presentation. I think the biggest thing we want to think about are the warning signs here. Using the things are going to lead you to answer on the boards, which is effectively to send a patient very quickly for examination by ophthalmologists. So any time patient has a change in visual acuity which is associated with clarity, SUVs or coma. A severe foreign body sensation prevents from keeping an eye open. Right the score itis if the patient people is fixed or they have a headache with not sound of glaucoma, similar flesh which we see here. I'm also warrant a very urgent evaluation because this occurs in spare itis, hepatitis or blocked call. So in terms of symptoms for a peaceful arthritis, right? This is the most common one. Again, we see that the redness is not starting at the center of the eye near the rubio, goes after the site can be one or both eyes, irritation, itching, burning and pain to pal patient. You can have injection of vessels. You can even have small nodule pictured here, there's no impairment in vision. This one parallels disease activity and management is top there's no threat to the site here and you should treat the DVD Score Itis. This is severe one. It impairs vision. It's a constant pain that worsens at night. It relates to the face because the extra ocular muscles and surged into the square us when her patient moves their eyes. The pain worsens. This pain will often limit their activity. Can be anterior with widespread erythema or post through without our athena. So again pain with our movement impaired vision. Immediately should require a sentence. The ophthalmologist and sprays does not parallel you ve this 25-3% of patients it can perceive the diagnosis and it can be associated with arthritis where the female predominance and so therefore it does not parallel disease activity. An I. V. D. These patients can often have a posterior project. You have to have high clinical suspicion it can occur bilaterally contra lateral life. You see pain, you see redness maybe floaters visual loss and you have to think about that. Especially again post your retirement corneal clouding contract title injection again does not parallel disease activity. The answer always for diagnosis, referral to up though. This is that slit lamp exam. Yeah with a dilated conference the treatment is prompt steroid therapy and cyclo please chicks we have to worry about secondary glaucoma and blindness. If not treated rapidly. IBD patients are often factor So for the final question A 56 year old female of all sort of colitis walks into your office complaining of a foreign body sensation. She has been managed on Solomon compounds last year but recently began having diarrhea. She has no change in visual acuity with normal people. Every response based on this finding the correct plan is to or for urgently to opt in evaluate her diarrhea. Start our chairs begin systemic corticosteroids to treat her eye and a diarrhea start topical steroids, cyclops allegiance and refer to alpha. The answer is B, evaluate her diarrhea and start artificial cheers by the picture we can see very clearly. This is arthritis relating to a disease flare. So controlling that flare is going to be the most important thing to the treatment of the disease and this is not threatening eyesight and therefore is not requiring an urgent. But that will conclude this.