Clinical GI – Intestinal Tract – Part 1 PDF

Clinical GI – Intestinal Tract – Part 1 Leonard Mankin, MD, FACP Associate Program Director Legacy Health, Portland, OR Associate Professor of Medicine Oregon Health & Science University Assistant Professor of Medicine Western COMP-NW...

Clinical GI – Intestinal Tract – Part 1 Leonard Mankin, MD, FACP Associate Program Director Legacy Health, Portland, OR Associate Professor of Medicine Oregon Health & Science University Assistant Professor of Medicine Western COMP-NW [email protected]  Objectives Understand the epidemiology, presenting symptoms, diagnostic features, complications and treatment of inflammatory bowel disease Outline key similarities and differences between Crohn’s disease and ulcerative colitis Identify the major causes of lower GI bleeding and the various clinical presentations and treatments of those entities  Outline IBD - Crohn’s disease - Ulcerative colitis Lower GI Bleeding - Diverticular disease - Ischemic colitis - Infectious colitis - Angiodysplasia - Hemorrhoids Inflammatory Bowel Disease Inflammatory Bowel Disease (IBD) Comprised of 2 major disorders – Crohn’s disease and ulcerative colitis Idiopathic inflammatory process with variable severity and course Affects 3.1 million in US (1.3%) Bimodal age distribution of onset (15-30 yrs and 50-80 yrs)  IBD Risk Factors - Genetics Strongly hereditary - first degree relative with 3-20 times increased risk of IBD 20% of people with IBD have another family member with IBD No distinct loci for susceptibility, appears to involve interactions amongst multiple genetic loci  Who gets IBD? Developed nations Jews > Non-Jews Whites > African American > Asian/Hispanic  Who gets IBD? Smoking - risk for Crohn’s, worse disease outcomes - risk for UC (protective!) Diet ( with high fats and low fruit/veg/fiber) Others less clear (stress, poor sleep, NSAIDs, OCPs, obesity, appendectomy) Crohn’s Disease  Crohn’s Disease - distribution Can involve any part of the GI tract, from mouth to anus Distribution is often non-contiguous, described as having “skip lesions”  Crohn’s Disease – distribution 80% with small bowel involvement (usually distal ileum) 50% have ileum and colonic disease (ileocolitis) 20% with disease limited to colon 33% with perianal disease 5-15% with involvement of upper GI tract  Crohn’s Disease - features Characterized by transmural inflammation, i.e., penetrates the muscularis mucosa Transmural involvement leads to serious complications of fibrosis, strictures, sinus tracts, fistulas, and perforations  Cobblestone appearance Normal colonic mucosa Crohn’s disease  Crohn’s – Clinical Presentation Pts often have non-specific sx over years prior to dx: - Crampy abdominal pains - Prolonged diarrhea episodes - Fatigue - Fevers - Weight loss - Lower GI bleeding (usually only in cases with significant colitis)  Crohn’s - Complications Partial small bowel obstruction – full thickness inflammation can lead to fibrosis, edema and narrowing of lumen Rx: bowel rest, IV fluids, nasogastric tube decompression, steroids Surgery for non-resolution (last resort) Avoid opioids and antidiarrheal agents! Dx? Small bowel obstruction in Crohn’s with multiple air-fluid levels CT scan showing SBO in Crohn’s with dilated loops of bowel  Crohn’s - Complications Peritonitis – Microperforations result in inflammation and infection, usually localized around bowels and mesentery Rx: bowel rest and IV antibiotics Surgery as last resort  Crohn’s – Complications Sinus tracts may end in a walled off area that is sterile (phlegmon) or infected (abscess) Sinus tracts that penetrate the serosa may form connections to other organs, called fistulas. Common fistula types include: - Intestine to bladder (enterovesical) - Intestine to skin (enterocutaneous) - Intestine to intestine (enteroenteric) - Intestine to vagina (enterovaginal) Rectovesicular fistula seen on barium enema Enterocutaneous fistulae  Crohn’s - Complications Colon cancer - Crohn’s disease pts with > 30% colonic involvement have risk Pts with colonic involvement should undergo initial screening colonoscopy beginning 8 years after dx Frequency of subsequent colonoscopy depends on disease activity, duration and % of colon involved  Crohn’s and Surgery Complications requiring surgery are exceedingly common! - 10-year risk of surgery is 50%!!! Surgery is not curative Surgery begets surgery! – reoperation rates: - 24% at 5 years - 35% at 10 years Gastroenterology 2013;145(5):996-1006 Ulcerative Colitis  Ulcerative Colitis (UC) Recurrent inflammatory state of the superficial layers of the colon Bloody diarrhea is the hallmark feature of the disease Like Crohn’s disease, many symptoms are non-specific (episodic diarrhea, abdominal pains, fatigue, fever)  UC – gross features Inflammation of the superficial mucosa of the colon results in edema, erythema, pseudopolyps and ulcerations Loss of colonic haustra results in a “lead pipe” appearance on imaging studies  UC – gross appearance A - Ulcerative changes of the superficial mucosa B & C – erythema, loss of vascular markings, and formation of pseudopolyps D – normal colon UpToDate accessed 12/30/2021 D  Normal Barium Enema Jhurads4anatomy.com  Lead Pipe Appearance in UC www.stepwards.com  UC - Distribution Almost always begins at the anorectal junction, with varying degree of contiguous proximal involvement up to the ileocecal valve No skip lesions! Rarely, can involve the terminal ileum, known as “backwash ileitis”  UC – Major Complications Severe bleeding in 10%, causing iron deficiency anemia, need for transfusions Fulminant colitis – severe inflammation with paralytic ileus Toxic megacolon – Colonic distention >6 cm with fever, pains,  WBC, and may result in perforation – extremely high mortality!  UC – Major Complications Colon cancer – increased risk after >8 years with disease. Higher risk with: - Long duration of disease (up to 30% at 30 years) - Very active disease - Pancolitis Screening colonoscopy recommended for UC starting at 8 years from time of diagnosis Am J Gastroenterol 2010;105:2405-2411 Extra-intestinal Manifestations of IBD Extraintestinal Manifestations of IBD IBD can affect multiple organ systems including the mouth, skin, eyes, joints and hepatobiliary system Unclear why? Direct genetic affect on other organs vs autoimmune reaction Affects ~ 25% of all people with IBD over course of their disease Crohn’s Disease – Oral lesions Aphthous ulcers Inflammation of lips Skin Manifestations of IBD  IBD and the Skin – E. nodosum Erythema nodosum – subcutaneous, tender erythematous nodules on the extensor surfaces (shins) Many causes of E nodosum, not just IBD! Most common derm manifestation of IBD Rash presence mimics IBD activity Erythema nodosum Skin Manifestations of IBD IBD and the Skin – P. gangrenosum Pyoderma gangrenosum – large, painful deep ulcers of the skin, usually on legs 2nd most common derm finding in IBD Rash activity is independent of IBD disease severity  Pyoderma gangrenosum N Eng J Med 2018;379:e7  IBD and the Eye Episcleritis and uveitis - inflammation of the eye layers underlying the conjunctiva The most common ocular manifestation of IBD, but not specific to IBD Does not threaten vision in any way Presence mimics IBD activity Episcleritis  IBD and the Joints Most frequent extraintestinal manifestation of IBD Nonspecific pains in large joints, worse during disease flares Considered a seronegative spondylo- arthropathy, often HLA-B27+, with manifestations similar to ankylosing spondylitis (spine, sacroiliac joint)  IBD and the Joints Normal sacroiliac joints Bilateral sacroiliitis  IBD and the Hepatobiliary System Primary sclerosing cholangitis (PSC) – inflammatory condition of bile ducts causing scarring and 20 hepatic injury No effective medical therapy, only cure is liver transplant! Median survival 10-21 yrs 5% of UC patients get PSC 90% of PSC patients have UC Primary Sclerosing Cholangitis  IBD and the hepatobiliary system Cholelithiasis – gallstones form in patients with terminal ileitis or after ileal resection Malabsorption of bile salts causes a reduction in the ratio of bile salts to cholesterol gallstones Only seen in Crohn’s disease, not UC Gallstones in Crohn’s disease Diagnosis of IBD  IBD – Dx Dx of IBD is not always straightforward Hx and Family Hx very important Must rule out other conditions, including infectious colitis Labs: CBC, ESR, CRP, fecal calprotectin or fecal lactoferrin, stool studies for infection IBD – Biomarkers of Disease Activity C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) – helpful measures of systemic inflammation, generally elevated in flares Elevations not specific for IBD, as many diseases can cause systemic inflammation Am J Gastro 2015;110:802-819 IBD – Biomarkers of Disease Activity Fecal Calprotectin (FC) and Stool Lactoferrin (SL) – proteins released into the intestinal lumen as a consequence of leukocyte activity More sensitive and specific for IBD Particularly helpful at following disease activity during treatment Am J Gastro 2015;110:802-819  IBD – Dx For pts with predominant diarrhea, colonoscopy with biopsy is gold standard For chronic abdominal pains and suspected small intestinal involvement, imaging studies (Upper GI barium study with SBFT, CT or MR enterography) Pattern of involvement helpful (presence of skip lesions), but still may be difficult to distinguish UC from Crohn’s  Antibody Testing in IBD Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) and anti- Saccharomyces cervisiae (ASCA) are also helpful at establishing a dx Antibody Sensitivity Specificity (%) (%) p-ANCA 50 95 ASCA 60 91 Am J Gastroenterol 2001;96-730  Distinguishing Crohn’s from UC p-ANCA + tends to point more toward UC, while ASCA+ suggests dx of Crohn’s Antibody Sensitivity Specificity (%) (%) p-ANCA+/ASCA-/UC+ 44 98 p-ANCA-/ASCA+/CD+ 56 92 Am J Gastroenterol 2001;96-730  Crohn’s vs UC - Histology www.stepwards.com Treatment of IBD  Treatment of IBD Initial goal is to achieve remission (induction therapy) Subsequent goal is to maintain quiescent phase for as long as possible with as little drug as possible (maintenance therapy) Treatment of UC  Rx for UC is by Disease Severity Mild to moderate disease - < 4-6 BM/day, little or no blood in stool, mild anemia, mild elevations in ESR, CRP and/or fecal calprotectin, absence of systemic toxicity Severe disease - > 6 BM/day, fevers, tachycardia, significant anemia requiring transfusion,  CRP/ESR/fecal calprotectin, weight loss UC Rx – Mild to Moderate Disease Majority achieve remission with use of anti-inflammatory agents: 1. 5-ASA derivatives - Mesalamine - Sulfasalazine 2. Glucocorticoids Distal disease – suppository or enema Proximal disease – oral therapy  Immunologics for Severe Disease 1. Anti-TNF agents (infliximab, adalimumab, golimumab) 2. Immunomodulators (6-mercaptopurine, azathioprine, methotrexate) 3. Anti-integrin agent (vedolizumab) 4. Anti-interleukin agent (ustekinumab)  Treatment of UC - Colectomy Colectomy is curative in UC (!), but will have loose stools/diarrhea for life Indications: - Failure to respond or intolerance to medical Rx - Fulminant colitis/toxic megacolon/perforation - Uncontrolled bleeding - Multifocal dysplasia or cancer Ileal Pouch Anal Anastamosis for UC Treatment of Crohn’s  Treatment of Crohn’s Disease Similar approach as UC with use of same medications More complicated due to wider distribution of disease and higher potential for systemic complications (e.g. abscesses, intestinal obstruction, peritonitis, malabsorption and weight loss)  Rx - mild Crohn’s Oral steroids are generally first-line for inducing remission 5-ASA drugs used secondarily Once remission is achieved, taper down/off steroids and monitor with every 6-month colonoscopy and inflammatory markers Rx - moderate to severe Crohn’s Start with biologic agents (usu. combo of TNF-alpha inhibitors + immunomodulator) ± glucocorticoids Maintenance of remission – taper off steroid, maintain on biologic monotherapy or combination therapy with ongoing surveillance (colonoscopy and disease markers)  Crohn’s disease - surgery A last resort for disease processes refractory to medical interventions: - Perforation/Abscess - Fistula - Hemorrhage - Severe stricture - neoplasm 10-year risk for surgery is about 50%! Gastroenterology 2013;145:996  UC vs Crohn’s Quick Summary  Feature Ulcerative Colitis Crohn’s Disease Location Colon, almost always in the Entire GI tract, almost rectum always in ileum Pattern Uniform disease Uneven, can have “skip involvement, from rectum lesions” proximally Histology Crypt abscesses Non-caseating granulomas Lesions Mucosal ulcers Transmural ulcers Fibrosis, perforations, No Yes fistulas Bowel wall Thin, loss of haustra causes Thickened, with “lead pipe” appearance of cobblestone appearance colon Cigarette smoking  disease severity Increases risk of disease development/flare Colorectal Cancer Risk ↑↑ ↑ if colon is affected  Feature Ulcerative Colitis Crohn’s Disease Hepatobiliary Primary sclerosing Cholelithiasis cholangitis GI Bleeding Bloody diarrhea common Usually microscopic, gross only with colitis Antibodies p-ANCA + ASCA + Toxic Megacolon Yes Rare Diarrhea +++ + (bloody) (bile salt malabsorption) Anemia +++ + (blood loss) (chronic inflammation, malabsorption) Malabsorption/(SIBO) No Yes Surgery can be curative Yes Never, often leads to more surgery! Lower GI Bleeding  Lower GI Bleeding Hematochezia = Bright red or maroon-colored blood from the rectum Hematochezia sources: - Colon (76%) - Small bowel (9%) - Above the ligament of Treitz (11%) - Unknown (6%)  Melena Digested blood from the upper GI tract will present as a black stool with a tar- like consistency and distinctive odor On rare occasion, melena can result from lower GI tract bleeding with very slow transit What else can give you dark stools? Lower GI Bleeding – Common Causes Diverticulosis – most common cause! Colitis (ischemic, infectious, inflammatory) Hemorrhoids Colon cancer or polyps Angiodysplasia N Eng J Med 2017;376:1054-1063 Diverticular Disease - definitions Diverticulum – a small pouch protruding from the intestinal wall, most common in sigmoid colon Diverticulosis – Presence of diverticuli, may be asymptomatic, or may cause bleeding or pain Diverticulitis – inflammation of a diverticulum, typically from infection www.singaporeclinic.com  Diverticular disease - risks Age (