[00:29]
Hello, I’m Dr. Benjamin Cohen and welcome to IBDIQ, part of The IBD Project by Takeda, where we’re coming together to help enhance expertise in IBD care—right from the start.
Today, we’ll introduce you to inflammatory bowel disease, or IBD, its subtypes, and clinical implications. And by the end, you’ll be able to recognize key features of Crohn’s disease and ulcerative colitis, identify red flag symptoms, and distinguish conditions mimicking IBD. We will also explore the connection between extra-intestinal manifestations and disease activity, considering their impact on overall management of IBD. And finally, we’ll delve into understanding the impact of IBD on quality of life and how it shapes treatment strategies.
[01:09]
IBD is a worldwide healthcare issue with increasing prevalence in the United States and across the world.1
Recent findings from a US-based study using Medicare, Medicaid, and two commercial health insurance companies’ administrative claims data from 2007 to 2017, 1999 to 2012, 2006 to 2018, and 2000 to 2017, respectively, show that the incidence of IBD tends to peak in the third decade of life and then decreases to a level that is stable through the fourth to eighth decades of life.2
In the United States, the prevalence of IBD was 721 per 100,000 people, which when extrapolated to the 2020 US Census population is an estimated 2.4 to 2.7 million Americans with IBD.2
And while prevalence was greater among white Americans,2 studies have shown that minority patients are diagnosed at older ages, or present with complications or more advanced disease, indicating delayed diagnoses.3
[02:06]
IBD is comprised of two major forms, Crohn’s disease and ulcerative colitis, which are distinct relapsing inflammatory diseases of the bowel.4 While the pathogenesis of IBD remains unknown, it is likely that a combination of patient and environmental factors contribute to the abnormal immune response that drives disease progression in IBD.
Research has indicated a role for a patient’s genetics and gut microbiome in contributing to the underlying pathophysiology in IBD.4
Genetic research has identified up to 240 IBD-associated gene loci.5 Identified genes include genes that are involved in the regulation of autophagy, T-cell immune responses, and proinflammatory cytokines.4,5
The gut microbiome in patients with IBD is also thought to be a contributing factor, as patients with IBD show significantly reduced flora biodiversity compared to healthy controls.4
[02:57]
Looking outside of the patient, multiple environmental factors have been identified as risk factors for IBD such as smoking, diet, drugs, and stress.4 However, it’s important to note that not all environmental factors contribute the same risk for development of UC or Crohn’s disease. For example, smoking has a protective effect on the development of UC with a lower rate of relapse, but increases the risks of Crohn’s disease and is associated with higher rate of postoperative disease.4
Dysfunctions of innate and adaptive immunity combine to drive the aberrant intestinal inflammatory response that is characteristic of IBD.4,5
Early recognition of Crohn’s disease is critically important to optimize outcomes.6
A growing body of evidence has shown that treatment for Crohn’s disease in its early stages is more effective than treating the disease at a later point.6
[03:44]
We’ve come to recognize a window of opportunity after diagnosis where if we treat inflammation effectively, then we may be able to prevent long-term complications such as strictures, fistulas, abscesses, and the need for surgery in Crohn’s disease.6
Though there’s less evidence for this window of opportunity in patients with UC, it’s still considered a progressive disease.6 Several studies have demonstrated that uncontrolled UC is associated with impaired gastrointestinal functioning and structural damage.7 Introducing biologic therapies early in UC management could help patients achieve symptomatic remission and mucosal healing.7
Patients with UC typically present with rectal bleeding, frequent stools, and urgency.8
Patients with proctitis or rectal inflammation can present with tenesmus, which can be described as a sensation of incomplete evacuation where one must go to the bathroom, but little to no stool comes out.8 Approximately 30% to 60% of patients may present with proctitis alone.
[04:42]
16% to 45% of patients may present with left-sided colitis. Symptoms may mimic proctitis, with the addition of abdominal cramping and diarrhea during bowel movements.8
And 15% to 35% of diagnosed patients may present with extensive colitis involving most of the colon.8 Patients may experience additional constitutional symptoms, fatigue, and fever.
Guidelines recommend obtaining a colonoscopy and biopsies of affected and unaffected areas to confirm UC diagnosis and disease extent.9,10
Crohn’s disease can affect any part of the digestive tract from the mouth to the anus but most commonly involves the terminal ileum.11 Unlike UC, affected areas in Crohn’s disease can be discontinuous.
The diagnosis of Crohn’s disease is based on a combination of symptoms and endoscopic examination with histologic confirmation of disease.11 Cross-sectional imaging is then used to accurately stage the disease extent and phenotype.
[05:35]
The different phenotypes of Crohn’s disease include inflammatory, stricturing, and fistulizing.12 In addition to these phenotypes, patients can develop perianal disease.
A diagnosis of Crohn’s disease should be considered in any patient who presents with chronic diarrhea, abdominal pain or tenderness, or weight loss.11
Patients with inflammatory Crohn’s disease typically present with diarrhea, abdominal pain, weight loss, fatigue, and other constitutional symptoms.12
Patients with stricturing disease may have obstructive symptoms, including postprandial pain, bloating, nausea, and vomiting.11
Patients with penetrating disease can have similar symptoms to inflammatory and stricturing disease, but may also present with symptoms related to fistulas, such as stool or air in the urine, dyspareunia, fecal discharge from the vagina, or abdominal abscess.11
Cross-sectional imaging plays a pivotal role in identifying stricturing and penetrating complications in Crohn’s disease.11
[06:30]
UC and Crohn’s disease have characteristic features that help to differentiate them.8
UC only involves the colon and is characterized by rectal involvement with continuous inflammation extending proximally.8 UC is also characterized by damage to the mucosal barrier with diffuse ulceration, granularity, friability, and bleeding. In UC, no penetrating features like fistulas are observed, and granulomas are not found.8,11 Smoking tends to have a protective effect in UC.8
On the other hand, Crohn’s disease can affect any part of the digestive tract from the mouth to the anus.11 The rectum may be spared,13 and there can be patchy areas with non-contiguous involvement.11 Inflammation in Crohn’s disease is transmural, which is why penetrating features like fistulas and abscesses may develop.12 In Crohn’s disease, granulomas are pathognomonic, and ulcers tend to be more serpiginous with a cobblestone appearance.11 Unlike UC, smoking increases the risk of developing Crohn’s disease.
[07:27]
While I’ve described general patterns that can help differentiate UC and Crohn’s disease, there are important exceptions to the rules.13
While UC is classically considered to only affect the colon, patients can experience nonclassical presentations.13 For example, backwash ileitis is seen in some cases of UC.13 Patients with left-sided UC can have a discontinuous cecal or peri-appendiceal patch of inflammation.8,13 And pediatric patients can present with relative rectal sparing.13
Differentiating UC from Crohn’s disease becomes challenging when patients are already on medical therapy, since disease areas may have relative healing leading to a patchy presentation of UC.13
Additionally, very severe UC can present with deep ulcerations that look more like the transmural appearance of Crohn’s disease.13 Mild upper gastrointestinal tract inflammation can be present in patients with UC leading to confusion about whether the accurate diagnosis is Crohn’s disease.13
[08:21]
Finally, IBD in the setting of primary sclerosing cholangitis is a unique phenotype of IBD where patients can have relative rectal sparing, backwash ileitis, and different patterns of colonic distribution.14
Appropriately risk-stratifying prognosis in patients recently diagnosed with IBD is essential to inform the selection of the most appropriate treatment and monitoring strategies.15
Certain baseline clinical features are associated with a more aggressive disease course with a higher risk of progression and complications.15
Higher-risk patients require early control of inflammation with immune-modifying therapies.15 However, immunotherapy can be associated with significant healthcare costs and safety concerns. With that in mind, a risk/benefit analysis should be conducted for each patient to develop an individualized treatment plan. And this is something I typically make sure to discuss with my patients in a shared decision-making setting.
[09:11]
It’s important to differentiate between disease activity and severity in IBD.15 Disease activity pertains to the burden of inflammation at any point in time, while severity considers the disease phenotype and course, aiding in prognosis and complication prediction.
For example, a patient with low disease activity but high severity may require proactive and aggressive management despite minimal symptoms.15
In Crohn’s disease, clinical factors linked to a more severe course include more extensive disease, growth impairment in pediatric patients, young age at diagnosis, smoking, perianal disease, penetrating and stricturing phenotypes, long segments of ileal involvement, emergency presentations, the need for steroids, and serologic markers such as ASCA and the NOD2 mutation (though these are not routinely checked in practice).15
[10:02]
In UC, a more severe course is associated with extensive disease, young age at diagnosis, emergency presentations, need for steroids, and Clostridium difficile (also known as C. diff) or cytomegalovirus (also known as CMV) infection associated with it.15
As mentioned, disease activity refers to the degree of inflammation at any point in time.11,15 Disease activity scores are used to assess clinical needs and may inform therapy choices.11
Shown are examples of research tools, such as the Crohn’s Disease Activity Index (or CDAI) and the ACG Disease Activity Score for UC, which assess disease activity and help guide treatment decisions.9,15
[10:42]
For example, in Crohn’s disease we’ll want to ask about symptoms such as diarrhea, weight loss from baseline, abdominal pain or tenderness, nausea and vomiting, and presence of fever.15 In UC, we’ll want to assess stool frequency, degree of bleeding, and urgency in addition to assessing biomarkers and endoscopy.9
In UC, tools are designed to measure disease activity based on things like stool frequency, degree of bleeding, and urgency.9 In Crohn’s disease, disease activity tools are based on amount of weight loss, presence of abdominal pain or obstruction, and fever.15
It’s important to have open communication with patients to foster effective shared decision-making.15
The International Organization of Inflammatory Bowel Disease (or IO-IBD) has outlined Red Flag symptoms for Crohn’s disease that when present should prompt diagnostic workup for earlier identification.16
[11:33]
The items in the Red Flags Index include non-healing perianal fistula, nocturnal diarrhea, first-degree relative with IBD, significant weight loss (more than 5% of the body weight) in 3 months, chronic abdominal pain, low-grade fever, no abdominal pain 30 to 45 minutes after meals, predominantly after vegetables, and no rectal urgency.16
Combining the Red Flags symptom score with a fecal calprotectin assessment has been shown to have a high predictive value and significantly increase the sensitivity in screening for Crohn’s disease.17
While red flag symptoms and predictors of disease severity can heighten suspicion for IBD, it’s crucial to be aware of conditions that mimic IBD with similar presentations.18,19
The Crohn’s and Colitis Foundation put together a helpful visual abstract highlighting infectious and non-infectious IBD mimics.18
[12:21]
Examples of infectious mimics of IBD can include Yersinia, Tuberculosis, Amebiasis and Histoplasma.19
Additionally there are non-infectious mimics that should be ruled out such as small vessel vasculitis, Behcet's disease, segmental colitis associated with diverticulosis, and ischemic colitis.19
Additionally, certain medications—such as NSAIDs or immune checkpoint inhibitors—cause clinical symptoms and inflammation like that seen with IBD.19
When diagnosing and monitoring IBD, it’s important to assess for extra-intestinal manifestations, or EIMs, of the disease.20
EIMs are reported to occur in up to 50% of patients with IBD and may affect every system of the body.20
[13:06]
Classical EIMs encompass various manifestations, including eye-related conditions like uveitis, scleritis, and episcleritis, oral ulcerations, liver manifestations, such as primary sclerosing cholangitis and autoimmune hepatitis, rheumatologic manifestations, such as axial and non-axial spondyloarthropathy, and skin manifestations such as pyoderma gangrenosum, erythema nodosum, and Sweet’s syndrome.20
Other manifestations associated with IBD can include conditions like multiple sclerosis, interstitial lung disease, and myocarditis.20
Finally, there can be conditions that arise because of treatment or disease complications including psoriasiform reaction, pericarditis, pancreatitis, osteoporosis, and venous thromboembolism.20
[13:54]
EIMs can present at any time, but there is an increased likelihood with longer duration of disease.21
As shown in data from a prospective national Swiss IBD cohort study of 950 adult patients with a mean age at enrollment of 43 years, EIMs are common, affecting nearly 40% of patients with the most common EIMs being arthritis, uveitis, and aphthous stomatitis.22
EIMs can impact therapy selection for patients with IBD.21
We still have much to learn about EIMs, including why some parallel the IBD activity and others may be independent.21
For example, episcleritis and aphthous stomatitis are typically correlated with increased disease activity.21
On the other hand, ankylosing spondylitis and primary sclerosing cholangitis are independent of bowel inflammation.21
Others such as peripheral arthritis, pyoderma gangrenosum, and uveitis can be present either way.21
[14:48]
While not an EIM, IBD is linked with behavioral health comorbidities such as depression and anxiety.23
Studies have demonstrated alterations in the brain in both humans and animals experiencing gut inflammation.23 There is a potential biological mechanism linking gut inflammation to changes in mental health, including the role of vagal nerve signaling from the inflamed gut.
In patients with depression, various factors may contribute to the onset or exacerbation of IBD, including gut dysbiosis, impaired efferent signaling via the vagus nerve, and increasing levels of pro-inflammatory cytokines from peritoneal macrophages.23
[15:24]
IBD has an extensive impact on a patient’s quality of life due to EIMs like anemia and fatigue; fatigue, in particular, is strongly associated with poor health-related quality of life, depression, and absenteeism.20
A prospective study including patients aged 16 years or older diagnosed with IBD receiving ileocolonoscopy in the Canterbury or West Coast regions of New Zealand indicated disease severity is associated with psychological symptoms (such as stress, depression, and anxiety) and health-related quality of life.24
Patients with a higher disease severity index experienced increased stress levels, increased levels of depression and anxiety symptoms, worsened quality of life, and a more complicated disease course.24
The International Organization for the Study of IBD (or the IO-IBD) STRIDE-2 guidance, published in 2021, now formally recognizes the normalization of quality of life and the absence of disability as a long-term treatment target for patients with IBD.25
[16:23]
We’re fortunate to have had an explosion of IBD therapies over the last few years across several different drug classes.26-29 We now have TNF inhibitors, anti-cytokine therapies, anti-integrins, JAK inhibitors, and S1P receptor modulators. There are options within each drug class that are indicated for Crohn’s disease, UC, or both.27,28
My hope is that this brief overview of the diagnosis of IBD, conditions that serve as mimics and important EIMs will set the stage for the rest of this comprehensive program on IBD management.
The take home points I want to leave you with from this session are that incidence and prevalence of IBD are increasing and early diagnosis is critical to preventing downstream complications.1,6
Red flag symptoms should raise suspicion for IBD and trigger a diagnostic workup.16 However, clinical, pathologic, and radiologic assessment is needed to confirm diagnosis.30,31
Extra-intestinal manifestations of IBD are common and have implications for management, so it’s important to assess for these in the care of IBD patients.20,21
Lastly, treatment goals for IBD should include not just improvement in clinical symptoms and objective inflammation, but normalization of quality of life and disability.25
[17:32]
Thank you for your interest and for spending some time with IBDIQ today to help adapt to the evolving care needs of all IBD patients.
