Thursday, March 15, 2018

Resident Journal Review: Inflammatory Bowel Disease

Authors: Erica Bates, MD and Adeolu Ogunbodede, MD
Editors: Michael Bond, MD FAAEM and Kelly Maurelus, MD FAAEM
Originally Published: Common Sense March/April 2018

Inflammatory bowel disease (IBD), which includes both Crohn’s disease (CD) and ulcerative colitis (UC), is a potentially debilitating chronic inflammatory condition of the digestive tract that affects over one million Americans.[1] Individuals with IBD are at risk for a number of potentially serious complications which emergency physicians must be able to recognize and manage. Here we review several articles relevant to the care of this patient population.
Jung, Yoon Suk, Dong Il Park, Sung Noh Hong, Eun Ran Kim, Young Ho Kim, Jae Hee Cheon, Chang Soo Eun et al. "Predictors of urgent findings on abdominopelvic CT in patients with Crohn’s disease presenting to the emergency department." Digestive diseases and sciences 60, no. 4 (2015): 929-935.

Abdominal CT is a mainstay of emergency department (ED) evaluation for patients with known CD who present with gastrointestinal symptoms, but repeated CT scans expose these individuals to significant radiation over time. In this multicenter retrospective trial, the authors examined visits by patients with CD who underwent a CT abdomen/pelvis in 11 university EDs in Korea from 2002-2013. Their goal was to identify predictors of urgent CT findings that change management in this patient population.

Patients were excluded if the ED CT represented a new diagnosis of CD, if they did not present with a GI related complaint, or if there was insufficient data recorded. They identified 266 visits with a CT abdomen/pelvis for 155 patients with CD. The primary outcome was a composite of several outcomes, either related to the CD or not, requiring urgent or emergent intervention. These included new or worsening obstruction, abscess, perforation, or other diagnoses requiring intervention (such as appendicitis). One hundred and three of the 266 CTs had urgent or emergency findings (38.7%), with the most common diagnosis being abscess, followed by obstruction and perforation. Thirty-four (31.6%) CTs demonstrated evidence of worsening CD, such as inflammation, stricture, or fistula, but only 10 (3.8%) of these CTs caused a change in actual management, such as intravenous steroids. Seventy-eight (29%) of the CTs showed no change or improvement compared to prior imaging.

Statistically significant predictors of urgent or emergent findings on CT were history of stricturing/penetrating disease, heart rate >100, WBC >10,000, and CRP >2.5. Use of biologic agents was associated with reduced risk of urgent findings. Disease distribution, history of prior abscess, obstruction, or perforation, history of prior Crohn’s related surgery, a prior CT abdomen/pelvis in the previous 1 or 3 months, and degree of symptoms at the time of the ED visit were not predictive of urgent CT findings.

This study did not include results for patients who underwent CT after admission. Another limitation is the lack of data on CD patients who presented to the ED with gastrointestinal symptoms but did not undergo CT. Furthermore, certain data points, such as CRP, were not available for all patients. The study also took place in Korea, which may limit generalization of the results to a US population with different baseline characteristics. Overall, the results showed that a fairly high proportion of CD patients (42%) who undergo CT in the ED have urgent findings that change management in some way, and more information is needed to allow emergency providers to reliably identify which patients with CD and gastrointestinal complaints may be able to safely forgo CT.

Fumery, Mathurin, Cao Xiaocang, Luc Dauchet, Corinne Gower-Rousseau, Laurent Peyrin-Biroulet, and Jean-Frédéric Colombel. "Thromboembolic events and cardiovascular mortality in inflammatory bowel diseases: A meta-analysis of observational studies." Journal of Crohn's and Colitis 8, no. 6 (2014): 469-479.

Inflammatory bowel disease is associated with an increased risk of venous thromboembolism (VTE), which is thought to be a result of the inflammation itself. In this article, Fumery et al performed a meta-analysis of existing studies to examine the relative risk of VTE as well as arterial thromboembolism and cardiovascular mortality for patients with IBD compared to the general population.

The authors performed a literature search and identified peer-reviewed observational controlled studies of adult patients with IBD (CD or UC) which reported risk of thrombotic events expressed as odds ratios, relative risk or a Standardized Mortality Ratio for cardiovascular disease. Thirty-three eligible studies were included, with a total of 207,814 IBD patients and 5,774,898 control patients. Weighted pooled relative risk was then calculated for each outcome.

A total of 10 studies examined the relative risk of VTE in a total of 72,205 IBD patients vs 891,840 controls. IBD patients had a greater risk of VTE (RR 1.96, 95% CI 1.67-2.3). There was no significant difference between CD vs UC patients. IBD patients showed increased risk of both deep venous thrombosis (DVT) (RR 2.42, 95% CI 1.78-3.3) and pulmonary embolism (PE) (RR 2.53, CI 1.95-3.28). Nine studies showed no increased risk of arterial thromboses (RR 1.15, 95% CI 0.91-1.45). The studies reviewed demonstrated no increased risk of stroke, peripheral artery disease, ischemic heart disease, or cardiovascular mortality when compared with controls. There were no significant differences between CD and UC subgroups. Two studies did show an increased risk of mesenteric ischemia in IBD patients (RR 3.46, 95% CI 1.78-6.71).

The authors did identify certain limitations to this review. Statistical analysis of the pooled data revealed significant heterogeneity among the studies. Certain outcomes, such as mesenteric ischemia, were supported by a relatively small number of studies and patients. The studies included also included a multitude of different clinical settings, including hospitalized and ambulatory patients, and some had relatively short follow up periods. Importantly, the data was not sufficient to examine the effect of IBD medications on the primary outcomes, and further studies are needed. Nonetheless, this review does demonstrate an increased risk of VTE in IBD patients, which emergency providers should keep in mind when evaluating these patients for possible DVT/PE.

Vavricka, Stephan R., Alain Schoepfer, Michael Scharl, Peter L. Lakatos, Alexander Navarini, and Gerhard Rogler. "Extraintestinal manifestations of inflammatory bowel disease." Inflammatory bowel diseases 21, no. 8 (2015): 1982-1992.

IBD can be complicated by a number of extraintestinal manifestations involving multiple organ systems. In this review article, Vavricko et al highlighted common extraintestinal complications that may occur in addition to the primary intestinal disease activity. Up to 50% of patients experience at least one extraintestinal manifestation at some point, and a quarter occur before the diagnosis of IBD is established. High clinical suspicion is necessary not only for prompt diagnosis and treatment of these accompanying conditions, but also to evaluate for underlying IBD when appropriate.

Peripheral arthritis is seen in 5-10% of patients with UC and 10-20% of patients with CD. It is usually seronegative and may be pauciarticular (less than 5 large joints) or polyarticular (5 or more small joints, typically including the metacarpophalangeal joints). Pauciarticular arthritis is usually associated with IBD activity and self-limited in a matter of weeks, while polyarticular disease is not related to degree of intestinal disease activity and may persist for years. Treatments include steroid injections. Systemic NSAIDs should be avoided due to the associated risk of IBD exacerbation. Rarely, patients may also develop ankylosing spondylitis and sacroilitis. Unlike the peripheral arthritis, which is typically nondestructive, axial arthritis can cause permanent skeletal damage and limited spinal flexion. These patients may require referral to a rheumatologist for treatment with systemic immunosuppression independent of treatment of their underlying IBD.

Up to 15% of IBD patients experience cutaneous manifestations of their disease. Erythema nodosum, characterized by tender red or purple nodules usually found on the anterior lower extremities, is associated with IBD flares and is more common in women and in CD. It usually resolves with treatment of the underlying disease and can often be treated supportively with elevation, analgesia, and compression hose. In contrast, pyoderma gangrenosum is a rare and more serious skin condition seen more frequently in UC. It usually starts as a nodule or pustule that progresses to a deep ulcer with irregular edges. The ulcers may contain sterile purulent material. Biopsy is not required, but shows neutrophilic infiltration and dermolysis. It can be treated with topical or intralesional injected steroids, treatment of the underlying IBD, and moist dressings. More serious cases may require systemic treatment such as dapsone, steroids, or immunosuppression with azothiaprine, methotrexate, tacrolimus, etc. Surgical debridement may worsen pyoderma gangrenosum. Acute febrile neutrophilic dermatosis, Sweet’s Syndrome, is a rare condition characterized by a tender papular rash, leukocytosis, fever, arthritis, and neutrophilic infiltration on biopsy. It is usually treated with topical or systemic steroids.

Ocular complications occur in 2-5% of IBD patients. Episcleritis is an inflammation of the tissue between the sclera and conjunctiva. It is a benign condition which causes redness of the conjunctiva and does not require therapy beyond treatment of the underlying IBD. In contrast, scleritis is a painful inflammation of deeper layers of the eye which can lead to retinal detachment or vision loss. Patients should be referred to an ophthalmologist and often receive topical steroids in addition to treatment of the underlying disease. Uveitis, an inflammation of the middle chambers of the eye, is another vision-threatening ocular manifestation. It can be unilateral or bilateral and usually presents with eye pain, blurry vision, light sensitivity, and “cell and flare” in the anterior chamber on slit lamp exam in anterior uveitis. Treatment includes topical and systemic steroids as well as urgent ophthalmology referral.

Half of patients with IBD experience some form of hepatobiliary involvement, which can include fatty liver disease, hepatitis, cholestasis, gallstones, and autoimmune pancreatic disease. A feared biliary complication is primary sclerosing cholangitis, an inflammation of the biliary ducts which leads to irreversible fibrosis and stricturing with cholestasis and ultimately cirrhosis. It is more common in UC (2.4-7.5%) then CD. It is treated with ursodeoxycholic acid, but this has not been shown to alter the overall disease course. The ultimate treatment is liver transplant.

Tang, Ying M., and Christian D. Stone. "Clostridium difficile infection in inflammatory bowel disease: challenges in diagnosis and treatment." Clinical journal of gastroenterology 10, no. 2 (2017): 112-123.

Clostridium difficile Infection (CDI) is a gastrointestinal infection of growing prevalence in the United States. It is caused by a gram-positive spore-forming anaerobic bacillus which causes a disruption of the micro and macroscopic gut wall-interface leading to watery diarrhea. This diarrhea, and the associated inflammatory response, can cause marked fever, leukocytosis, sepsis, shock and even death in severe cases. CDI is recognized as the leading cause of gastrointestinal death today.

CDI is not only growing in prevalence amongst healthy individuals in the community, but is increasingly affecting the vulnerable population of individuals with inflammatory bowel disease. Those with diseases such as UC and CD are at much greater risk due to multiple factors including disruption of the gut flora, antibiotic use, repeated hospitalization, systemic immunosuppressants, and chronic inflammation which hinders the gut’s ability to fight off infective processes.

Diagnosis of c.difficile infection in a patient with IBD poses a complex diagnostic challenge, requiring a high index of clinical suspicion and correct testing modalities of stool. The authors stress the importance of performing PCR analysis of unformed stool due to its higher specificity (>95%) and sensitivity (>90%) versus older modalities of testing, such as enzyme immunoassay (EIA) and nucleic acid amplification tests (NAATs). Clinical suspicion trumps test results due to the increasing prevalence of positive PCR testing for presence of c.difficile toxin colonization without the presence of active infection. This is especially true in individuals with IBD due to higher colonization rates.

Tang et al then propose a practical algorithm for the diagnosis and treatment of individuals with IBD and diarrhea based on updated infectious disease guidelines and recent gastroenterology literature. The authors note important signs, symptoms and laboratory data required to classify a CDI as severe. These can include fever, hypotension, abdominal distension, lactic acidosis, leukocytosis or leukopenia, mental status changes or otherwise meeting admission criteria for the ICU. It is recommended that mild to moderate CDI be treated with metronidazole on first or second occurrence, and with oral vancomycin for severe disease. Severe complicated disease, which includes signs of intestinal obstruction, should be treated with oral and rectal vancomycin as well as intravenous metronidazole. Surgical consultation should be obtained early in patients with complex disease in event that colonic resection is warranted. For a third episode of recurrent CDI, a 24-day regimen of oral vancomycin is recommended. Fecal transplantation as well as fidaxomicin should be discussed in consultation with gastroenterology and infectious disease for patients with four or more occurrences.

Patients with IBD and c.difficile infection require a multidisciplinary approach to diagnosis and treatment. The authors note that high quality evidence is lacking to guide the use of antibiotics in patients who are often on chronic immunosuppressive therapy. They also caution the practitioner to consider treating an IBD patient with induction therapy if they are not improving in the face of treatment. Finally, the authors stress that continued diarrhea in a patient with underlying IBD does not necessarily signal treatment failure, and to be wary of the possibility of false positive tests in this challenging patient population.

Kucharzik, Torsten, Klaus Kannengiesser, and Frauke Petersen. "The use of ultrasound in inflammatory bowel disease." Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology 30, no. 2 (2017): 135.

One long term risk of IBD is the high cumulative doses of radiation these patients experience over the course of their lifetime due to repeated CT scans. MRI can provide a potential alternative without the risk of ionizing radiation, but its use is sometimes limited by cost and availability. In this article, the authors review the potential role of intestinal ultrasonography (US) in the management of CD and UC.

Intestinal bowel wall thickness on ultrasonography can be used as a proxy for inflammatory activity. Bowel wall thickness greater than 2mm of the small intestine or 3-4 for large bowel is generally considered abnormal. A thickness of 3mm for large bowel has a sensitivity of 88% and specificity of 93%; increasing this to 4mm reduces sensitivity to 75% but increases specificity to 97%. Loss of clear bowel wall layers on ultrasound can also indicate inflammation. In flares of CD, fibrofatty proliferation can also be seen on US as a hyperechoic area around actively inflamed bowel. Bedside color doppler US can be used to detect increased vascularity of the thickened bowel, which is also associated with active inflammation.

Intestinal US can be useful in detecting certain common complications of IBD, such as intestinal abscesses and fistula. Ultrasound has a sensitivity of 84% (95% CI 79-88%) and specificity of 93% (95% CI 89-95%) for abscess in CD, while it has a sensitivity of 67-87% and specificity ranging from 90-100% for fistulas. US can additionally be used to guide sampling of a suspected abscess. For perirectal fistulas, MRI and transrectal ultrasound have similar sensitivity.

There are several limitations to the use of intestinal US for IBD. Uniform standards do not exist for interpreting characteristics such as bowel vascularity, nor are there standards for the number and locations of views that should be obtained. Significant interobserver variation has been noted. Patient characteristics, such as body habitus and degree of bowel gas, may also limit US evaluation. Intestinal US is not a standard part of emergency bedside US training for many emergency providers in the US, who may not feel comfortable relying on these findings to assess for complications, and it is not universally available as a standard radiology exam. Nonetheless, intestinal US is a promising modality for the evaluation of IBD, and more study is needed on potential applications.

Patients with IBD are at risk for a number of potentially serious issues, from abscesses or c.difficile infections to thrombotic events and structural complications. Although CT scans frequently change management while assessing these patients, the risks of high cumulative lifetime radiation have prompted increased interest in intestinal ultrasound as a promising new modality to assess for inflammation and certain complications. Emergency providers must be familiar with the many possible presentations of this challenging condition.


1. Kappelman, Michael D., Kristen R. Moore, Jeffery K. Allen, and Suzanne F. Cook. "Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population." Digestive diseases and sciences 58, no. 2 (2013): 519-525.

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