Complications and Management Approaches

[00:30]

Hello, I’m Dr. Katie Falloon, 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.

In this video, we’ll cover 3 main areas to help you better understand extraintestinal manifestations, or EIMs, in patients with inflammatory bowel disease, or IBD. First, we’ll define what EIMs are and discuss how they occur. Next, we’ll look at how frequently EIMs happen and why they matter for patient care. Finally, we’ll review management considerations for common types of EIMs.

[01:05]

Now that we’ve set the stage, let’s begin by discussing what EIMs are and why they matter for patients with IBD.

EIMs in IBD represent an expanding area of research, gaining increased attention due to their impact on patients’ health as well as many remaining knowledge gaps.^1,2

EIMs are inflammatory manifestations that arise in tissues outside the gut in patients with IBD.³ EIMs are a relevant topic since they may significantly reduce a patient’s overall health and health-related quality of life.^1,4

EIMs can affect nearly any organ system beyond the gut.³ However, important manifestations to be aware of include those involving the musculoskeletal, ocular, cutaneous, and hepatobiliary systems—or the joints, eyes, skin, and liver and bile ducts.^3,5

EIMs may also impact other areas of the body, such as the cardiovascular system, lungs, and pancreas.^3,5 These manifestations may be challenging to diagnose as they may not always be readily clinically apparent.^3,6

While the underlying cause of EIMs is not fully understood, there are 2 common hypotheses that may explain how IBD leads to inflammation in other parts of the body.^3,5,6

[02:16]

The first is that EIMs may result from an extension of the immune response from the gastrointestinal tract.⁵ Here, the immune system may begin targeting proteins at extra-intestinal sites that are similar to those found in the gut.

The second thought is that EIMs may result from independent inflammatory events sharing common genetic or environmental risk factors with IBD.⁵ For instance, IBD inflammation and its risk factors (such as genetic predisposition or environmental exposures) may make a person more prone to inflammation elsewhere. This may be caused by IBD-related changes with systemic effects (such as alterations in microbial populations as well as immune cell populations and activity), which may then affect immune function at non-intestinal sites.

[03:04]

Let’s turn now to 2 studies that show how frequent EIMs may be in patients with IBD.

One of the studies is the US Study of Prospective Adult Research Cohort with IBD, or SPARC IBD for short.⁷ This retrospective analysis assessed the frequency of 5 EIMs using data from roughly 1,200 patients with IBD in the US who were enrolled from 2016 to 2021.

The SPARC IBD analysis showed that at least one of the 5 EIMs of interest occurred in approximately 30% of patients with Crohn’s disease (or CD) and 23% of patients with ulcerative colitis (or UC), which are the 2 main forms of IBD.⁷

The other study, known as the Swiss Inflammatory Bowel Disease Cohort Study, or Swiss IBD Cohort Study for short, collected EIM data from approximately 1,200 patients with IBD from 2006 to 2010 across multiple centers in Switzerland.⁸

[04:01]

It reported similar results on EIM frequency, as about 34% of patients with Crohn’s and 22% of patients with UC experienced at least 1 of the 8 EIMs assessed.⁸

The Swiss IBD Cohort study additionally documented the number of patients who experienced multiple EIMs.⁸

Among those with EIMs, approximately 28% of patients with Crohn’s disease and 25% of patients with UC experienced 2 EIMs.⁸ Approximately 11% of patients with Crohn’s disease and 9% of patients with UC experienced 3 to 5 EIMs.

The Swiss IBD Cohort study further examined when patients experienced EIMs.⁸ Of all the EIMs the study assessed, some arose in patients before their IBD diagnosis, while most arose years after their diagnosis. This potential for EIM occurrence at almost any timepoint highlights the importance of healthcare provider preparedness to identify and manage EIMs.^8,9

[05:05]

If a patient with IBD develops an EIM, their quality of life may be impacted.⁴ This was assessed in a German study, which surveyed the quality of life in 595 patients with IBD and compared the outcomes for those with active EIMs to those without.

The survey instrument used to assess quality of life, known as the Short Inflammatory Bowel Disease Questionnaire (or SIBDQ), measures the physical, social, and emotional impact of IBD.^4,10 Total SIBDQ scores range from 10 to 70, with lower scores indicating greater patient impairment. This study defined a score of 60 or higher as a normal quality of life.  

Analysis showed that among patients with IBD, those with active EIMs had a lower quality of life versus those without, as the median SIBDQ score in patients with active EIMs was lower.⁴ This suggests that EIMs may have a significant negative impact on quality of life in patients already struggling with IBD.^1,4

[06:10]

The informed use of EIM management approaches may help patients regain quality of life.^4,6 In my clinical practice, I collaborate with other specialists to support EIM diagnosis and management approaches, based on the patient's specific EIM type.^1,6

As mentioned, EIMs can affect various organ systems, so a collaborative approach can be beneficial.¹ A dermatologist may assist in identifying the cause of a skin nodule or lesion, an ophthalmologist may help to identify certain ocular manifestations via the use of a slit lamp examination, and a rheumatologist may provide expertise in diagnosing musculoskeletal conditions.^1,6 If a hepatic EIM occurs, consultation with a hepatologist may be needed as well.⁶ Thus, while gastroenterologists may become familiar with EIMs in IBD, specialist involvement can improve not only diagnostic accuracy but also subsequent management.¹ 

[07:11]

The US Expert Consensus Panel was established by myself and colleagues in 2021 to develop a standardized, collaborative approach to guide clinicians in addressing 5 major EIMs.¹ This panel brought together expert gastroenterologists, rheumatologists, ophthalmologists, dermatologists, and patient representatives to establish consensus regarding definitions and treatment targets for these EIMs of interest.

Despite the development of this consensus, there are no formal guidelines for EIM treatment in the United States.¹ However, recently published guidelines by the European Crohn’s and Colitis Organization (or ECCO) provide further clarity when discussing management recommendations.⁶ 

Let’s begin by reviewing the diagnosis and monitoring recommendations for common EIMs, identified by ECCO guidelines and the US Expert Consensus Panel, examining each organ system individually.

[08:11]

Axial spondyloarthritis and peripheral spondyloarthritis are two common EIMs which impact the musculoskeletal system.^6,8 

Patients with IBD who develop axial spondyloarthritis may present with back pain and spinal morning stiffness due to the inflammation in the sacroiliac joints and spine associated with this EIM type.^6,11 This inflammation, which may be visualized via magnetic resonance imaging (or MRI) or sometimes even via radiograph, may lead to subchondral bone marrow edema and bone formation on vertebrae, particularly in later stages of the disease if left untreated.^6,11-15

Those with peripheral spondyloarthritis typically present with joint inflammatory symptoms, which may occur in the upper or lower limbs or both .⁶ Commonly identified sites of involvement include the knees and hands, where signs of inflammation, such as fluid effusion, may be identified via MRI and other imaging methods.^3,6,11,16,17

[09:11]

For both axial and peripheral spondyloarthritis, the US Expert Consensus Panel and ECCO guidelines acknowledge diagnosis is based upon a combination of clinical signs and symptoms, classification criteria, and imaging results.^1,6,18 Rheumatology assessment can also be valuable in both establishing the diagnosis and monitoring disease activity over time, and is essential for axial spondylorarthritis.^1,18

Let’s now shift the discussion to EIMs which affect the skin.⁸ Commonly recognized EIMs in this category include erythema nodosum (or EN) and pyoderma gangrenosum (or PG). 

EN is characterized by erythematous, painful skin lesions or nodules of 1-5 centimeters in size.⁶ As shown by the images, lesions may appear more reddish or purplish to dark brown based on skin tone.^19,20

[10:06]

Patients with PG may present with tender lesions or papules that develop into deep ulcers, or open sores, of 2 to 20 centimeters that may produce pus.^{6, 21-24} PG ulcers may have a reddish or purple-brown border depending on the patient’s skin tone. 

Thus, awareness of visual differences in cutaneous EIMs can aid in timely diagnosis across patients with various skin tones.^21,25 

According to the ECCO guidelines and US Expert Consensus panel statements, cutaneous EIMs may initially be recognized by clinical examination^1,6. A dermatologist may also be involved, particularly for the more challenging diagnosis of PG. Monitoring may similarly be carried out through gastroenterologist or dermatologist visits depending on the type and severity of the EIM. 

Now, let’s discuss some common ocular EIMs—specifically uveitis, scleritis, and episcleritis.⁵ 

[11:04]

Uveitis involves painful inflammation of the middle layer of the eye, known as the uvea.^6,26 Uveitis may lead to blurry vision and cause the eye to appear red, with hazy white markings from inflammation.^26-29 

Scleritis, on the other hand, involves inflammation of the white part of the eye, or sclera.²⁶ Patients may experience eye redness and pain from this inflammation and the sclera may thicken.^26,30 

Lastly, episcleritis causes inflammation in the eye’s outer layer and may make the eye appear red or pink.^6,26,30 Episcleritis is considered to be a milder condition than uveitis and scleritis, which are associated with a risk of pain and vision loss.^5,6,30 

Statements from the US Expert Consensus panel and ECCO guidelines recommend ophthalmologist involvement in the diagnosis and monitoring of ocular conditions such as uveitis and scleritis.^1,6 While regular ophthalmology visits are not standard for all patients with IBD, recognition and rapid referral by the managing provider are encouraged as these conditions may be vision-threatening. 

[12:10]

Now, let’s turn to the final EIM type we’ll cover today—hepatobiliary EIMs—which includes a disease called primary sclerosing cholangitis (or PSC).^7,8 

PSC is a condition characterized by inflammation and fibrosis of bile ducts, which may lead to liver failure.^6,31

The importance of diagnosing PSC, even in asymptomatic patients, was suggested by a prospective national healthcare registry study in England, which examined over 280,000 patients with IBD.^6,32 This analysis showed patients with IBD and PSC had an approximately 3 times greater mortality rate than patients with IBD without PSC.³² 

The US Expert Consensus panel does not explore topics regarding PSC; however, according to ECCO guidelines, PSC diagnosis often begins with repeat blood tests which may reveal persistently elevated cholestatic liver enzymes, suggesting cholestasis.^1,6,33 From there, specialized imaging such as magnetic resonance cholangiopancreatography, along with other imaging and tissue sample tests, may be used to confirm PSC.^6,33

[13:21]

Hepatology evaluation and regular follow-up visits are recommended to facilitate diagnosis and determine the appropriate course of management, including if and when liver transplantation may be necessary.⁶ 

When considering management approaches, it is important to note that some EIMs can parallel IBD activity, such that symptoms generally resolve when IBD is controlled. Some EIMs can be independent of IBD activity, while others may or may not parallel IBD activity.^6,9,34-36 Recognizing these relationships may help guide treatment selection for these types of EIMs.⁶ 

Management depends on the type and severity of EIM.⁶ According to ECCO guidelines, some EIMs may be directly treated with specific medications for the EIM itself. However, for EIMs that parallel IBD activity, treating the underlying IBD may be the primary focus.

[14:17]

Supportive measures and medications for pain management may also be considered, depending on the EIM.⁶

The US Expert Consensus panel does not include medication recommendations for EIMs.¹

Healthcare professionals should consult individual product labels and consider patient-specific needs when developing a management recommendation.⁶

Since EIM research is continually evolving, upcoming trials may further reveal impact of various therapies on these complications.^2,37 Please refer to newly published guidelines and product labels for the most up-to-date treatment recommendations.

Now that we’ve explored what EIMs are, why they matter for patient care, and how these manifestations may be managed, let’s summarize what we learned.

[15:04]

EIMs are inflammatory conditions that occur outside the gut in patients with IBD and may reduce quality of life.^1,3,4 EIMs are common and may occur in patients before and years after IBD diagnosis.^7,8 Collaborative partnership between gastroenterologists and other specialists may aid in the diagnosis and management of different EIMs.¹ And lastly, current guidelines may provide insight on management options for different EIMs.^1,6 

Given the profound impact of EIMs on the lives of patients, I hope this overview can motivate improved identification and management of these conditions.

Thank you for your interest and for spending some time with IBDIQ today to help adapt to the evolving care needs of all patients with IBD.