30 Inflammatory Bowel Disease 2024 (1).pptx

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Inflammatory Diseases of the Bowel Department of Medicine and Pathology  LEARNING OUTCOMES 1. Define IBD (inflammatory bowel disease...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Inflammatory Diseases of the Bowel Department of Medicine and Pathology  LEARNING OUTCOMES 1. Define IBD (inflammatory bowel disease) - Pathology 2. Explain the pathophysiology of IBD – Pathology 3. State the risk factors associated with ulcerative colitis and Crohn’s disease - medicine 4. List the cardinal symptoms and signs of IBD - Medicine 5. Explain how each symptom and sign is caused in IBD - Medicine 6. Develop a differential diagnosis for IBD - medicine 7. Outline overarching principles of investigation and management of IBD – medicine 8. Describe the gross and microscopic appearance of ulcerative colitis and Crohn’s disease - Pathology 9. State the complications of IBD - Pathology WHAT IS THE DIFFERENTIAL DIAGNOSIS OF COLITIS? ANSWER – QUESTION 1 Differential diagnosis of Colitis: Idiopathic Inflammatory Bowel Disease  Ulcerative Colitis  Crohn’s Disease Infection  Viruses, bacterial, protozoan  Antibiotic associated colitis (clostridium) Ischaemia  Occlusive: Thrombi / embolism  Non occlusive: cardiac failure / vasculitis / shock / radiation  ANSWER – QUESTION 1  Diverticular disease  Malignancy (e.g. adenocarcinoma)  Drugs (e.g. NSAIDs)  Irritable bowel syndrome, lymphocytic colitis In this age group, with this presentation, the most likely diagnoses are Idiopathic IBD Acute infectious colitis  Drugs (e.g. NSAIDs) WHAT ARE THE MICROSCOPIC CHANGES YOU WOULD EXPECT TO FIND IN CROHN'S DISEASE? POINT SOLUTIONS - ANSWER 2 Transmural inflammation, patchy (skip lesions), tip of tongue to tip of anus Ulceration Acute inflammation  Cryptitis  Crypt abscesses Granulomas (40-60% of cases) Fibrosis LEARNING OUTCOME 1 Define inflammatory bowel disease IDIOPATHIC INFLAMMATORY BOWEL DISEASE DEFINITION Definition: Chronic, relapsing inflammatory intestinal disorders of unknown cause  Crohn’s disease  Ulcerative colitis Incidence of both Crohn’s and ulcerative colitis is rising Possible factors in their development:  Genetic susceptibility  Intestinal flora  Abnormal T-cell response  Other factors - emotional stress, diet? LEARNING OUTCOME 2 Explore the pathophysiology of IBD  IDIOPATHIC INFLAMMATORY BOWEL DISEASE - PATHOPHYSIOLOGY Alteration of bacterial flora, increase in E.coli adherence to ileal epithelial cells “Leaky” epithelium, more luminal antigens entering, causing inappropriate immune response Final common pathway is inflammation  Impaired integrity of mucosa/mucosal destruction  Loss of absorptive function  Increased secretory function LEARNING OUTCOME 3 State the risk factors associated with ulcerative colitis and Crohn’s disease RISK FACTORS Family History – Influential but not the only consideration – Multiple susceptibility loci for both disorders – environmental and epigenetic interactions are key Recent smoking cessation (UC) Western/developed countries Jewish ethnicity: Ashkenazi Bimodal distribution, predominantly 2nd and 3rd decades of life, smaller second peak later in life ~60s LEARNING OUTCOME 4 & 5 List the cardinal symptoms and signs of IBD Explain how each symptom and sign is caused in IBD Crohn's Disease Ulcerative Colitis​ Any part of GIT: Gum to Bum Large intestine only​ Discontinuous Continuous inflammation (rectum patchy inflammation (skip first working backwards)​ lesion) Mucosa and submucosa layers Cobblestone only Terminal ileum most commonly effected section of bowel Transmural (full thickness of bowel wall) Fistulae Abscesses Perianal disease Strictures CARDINAL SYMPTOMS Diarrhoea: (Mucosal Damage, increased secretion) – More than 30 days, range of severity – Bloody (UC >CD). Bloody diarrhoea is the classical presenting symptom of UC – Urgency, frequency, tenesmus, pain relieved by defaecation (where inflammation affects mostly the rectum and sigmoid colon). – Mucous Weight loss (CD>UC) (Catabolism, malabsorption) Fever Abdominal Pain (CD>UC) Perianal pain and abscess (CD) Extraintestinal features Fatigue Delayed puberty These symptoms can be common to both CD and UC, but there are certain features which will aid distinction. SYMPTOMS: ULCERATIVE COLITIS INFLAMMATION OF THE INNER LINING OF BOWEL Bloody diarrhoea is the classical presenting symptom of ulcerative colitis, although a small number of patients have constipation. Other less frequent symptoms include fever, cramping abdominal pain, weight loss and general malaise. Where inflammation affects mainly the rectum and sigmoid colon, patients may complain of frequency, urgency, tenesmus, and pain, which is relieved by defecation.  SYMPTOMS: CROHN’S DISEASE INFLAMMATION OF THE WHOLE BOWEL WALL Patients with Crohn’s disease affecting the colon only may have symptoms similar to those of ulcerative colitis, such as diarrhoea, but when the small intestine is affected a number of differences are observed. Abdominal pain is common, usually occurring in the right lower quadrant (site of terminal ileum). Patients may also present with signs of intestinal obstruction (due to inflammation and stricturing). In addition, there may be severe bleeding, marked pyrexia, weight loss and general malaise. Fistulae can occur in other segments of bowel, various internal organs, or the skin. Perianal disease (fistulae, abscesses and skin tags) is often a presenting symptom SIGNS Sign Pathophysiology Low BMI Malabsorption due to small bowel involvement Clubbing Unclear, ?PDGF Pallor of palmar Anaemia: iron deficiency due to blood loss, creases/ malabsorption, B12 deficiency: terminal ileum conjunctivae inflammation leads to malabsorption of B12 Koilynchia Iron deficiency anaemia Scleritis/ 2-5% patients with IBD, burning/itching eyes or Episcleritis asymptomatic, injection of ciliary vessels, inflammation of episcleral tissues. Thought to be secondary to inflammatory process, antibodies against shared antigens/ molecular mimicry Uveitis Less common than episcleritis, 0.5-3%. More severe, frequently bilateral, posterior to the lens, insidious in onset, chronic in duration, F>M Cataracts Long term glucocorticoids SIGNS Signs Pathophysiology Mouth ulcers Inflammatory process, antibodies against shared antigens, molecular mimicry, also malnutrition and drug side effects. CD>UC Cirrhosis PSC: Primary sclerosing cholangitis, strong association with UC. Jaundice, hepatomegaly, splenomegaly may be evident. Inflammation, fibrosis, and stricturing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree Erythema raised, tender, red or violet subcutaneous nodules, Nodosum most often on extensor surfaces of lower limbs. Usually occurs with intestinal disease flares. Inflammatory process, antibodies against shared antigens, molecular mimicry, Pyoderma single or multiple erythematous papules or Gangrenosum pustules that are often preceded by trauma to the skin, tends not to parallel disease activity. Clubbing PSC Episcleritis Aphthous ulcers Aphthous ulcers Pyoderma Gangrenosum Erythema Nodosum LEARNING OUTCOME 6 Develop a differential diagnosis for IBD DIFFERENTIAL DIAGNOSIS: COLITIS What is the differential diagnosis of colitis? The “I’s” What are causes of inflammation? Infection Ischaemia Immune Irritants (Toxins) Idiopathic DIFFERENTIAL DIAGNOSIS OF COLITIS 1. Idiopathic Inflammatory Bowel Disease Ulcerative Colitis Crohn’s Disease 2. Infective colitis – usually acute onset and short history Bacterial – e.g. yersinia, E Coli, salmonella, Staph aureus, Campylobacter Viral – e.g. rotavirus, norovirus Protozoan – e.g. entamoeba histolytica Infectious colitis can mimic or precipitate an acute onset of idiopathic Chronic IBD. Pseudomembranous colitis – history of systemic antibiotic use – Clostridium difficile overgrowth DIFFERENTIAL DIAGNOSIS: COLITIS 3. Ischaemic colitis Usually older patients, cardiac history, sudden pain & bloody diarrhoea Occlusive: Thrombosis, embolism Vasculitis: Systemic vasculitis can also cause ischaemia by leading to arterial thrombosis eg. Polyarteritis nodosa, SLE Non-occlusive: cardiac failure, shock, radiation etc. Most common cause is a thrombus or embolus in the mesenteric artery 4. Diverticular Disease Left side colon/sigmoid, age usually >50yrs, Inflammatory changes may cause abscess, fibrosis and strictures mimicking malignant stricture 5. Malignancy 6. Drugs LEARNING OUTCOME 7 Outline overarching principles of investigation and management of IBD INVESTIGATIONS? WHAT ARE YOU LOOKING FOR AND WHY? Bloods: FBC, U&E CRP (inflammatory marker) Folate, B12 (malabsorption) Iron studies (which ones), (blood loss), Calcium, Mg LFTs Albumin (low in severe disease) INVESTIGATIONS Stool Samples: Faecal occult blood Stool culture for microorganisms (including Cl. difficile) Faecal calprotectin: protein found in neutrophils, indicates neutrophilic migration into intestinal tissue ie. inflammation Radiology/Direct Visualisation: Endoscopy + Bx (lower +/- upper), gold standard – Colonoscopy: Large bowel, can also access terminal ileum – OGD: If any upper GI symptoms SBFT – (Small Bowel Barium Follow Through) CT colonography if endoscopy difficult +/- CT scan Ultrasound – disease in ileum and colon Capsule endoscopy Colonoscopy: patchy areas of inflammation, biopsies taken for histology COLONOSCOPY OF COLITIS ULCERATIVE COLITIS: loss of vascular markings, erythema, petechiae, exudates, edema, erosions, touch friability, and spontaneous bleeding may be present. More severe cases may be associated with macro ulcerations, profuse bleeding, and copious exudates. Continuous. Mayo Score ISCHAEMIC COLITIS: Single Stripe Sign, scattered erythema, petechiae, erosion, ulceration, dark or dusky mucosa particularly in watershed areas. ENDOSCOPY FEATURES CROHN’S DISEASE Ulceration: – Deep, transmural – Aphthous Cobblestone mucosa – Ulcerated areas form the crevices and the normal tissue between them resembles cobblestones. Skip lesions (discontinuous) Normal appearing rectal mucosa Inflammation of terminal ileum (in the absence of colonic inflammation ie. can get back wash ileitis with UC) Aphthous ulcers COLON BIOPSY FINDINGS IN CROHN’S DISEASE Loss of architecture Cryptitis Crypt abscess Granulomas Acute AND Chronic changes LEARNING OUTCOME 7 Outline overarching principles of investigation and management of IBD Conservative Smoking Nutrition 5- ASA (Aminosalicyclic Acids) Mesalazine, Sulphasalazine. Induce and maintain remission in 30-35% patients with UC. Limited if any role in CD SE: Azoospermia, lymphopenia, BOOP, renal toxicity. Generally a relatively safe drug. Antibiotics Metronidazole Ciprofloxacin Steroids Oral, IV, PR. Used in short courses. Due to potential side effects, need to limit use with steroid sparing agents below. Consider bone protection. Immunosuppressants Azathioprine (Thiopurine) can maintain steroid free remission in 35-40% SE: myelosuppression, pancreatitis, erythema nodosum, infection, lymphoma. Methotrexate: Inhibition of dihydrofolate reductase, inhibiting nucleotide synthesis. Chemotherapy agent. SE: Neural tube defects, nausea, myelosuppression Cyclosporin: Inhibits T lymphocyte response. Biologics Anti-TNF (infliximab, adalimumab, golimumab). SE: Infection, reactivation of latent TB, lymphoma, skin cancers, psoriasis. Vedolizumab: a4B7 integrin inhibitor Ustekinumab: Anti IL 12, IL 23 Tofacitinib: JAK inhibitor Surgery  TREATMENT PYRAMID Severe Surgery Severe STEP UP TOP DOWN APPROACH Biologic APPROACH For low-risk patients with mild For high-risk patients with disease therapy severe disease, will treat Less potent medications with more potent with fewer side effects as first therapies at the risk of tier, progressing to more Immunosuppres more serious side potent medications with more effects, then scale back side effects sant therapy Steroids Mild Mild 5-ASA Antibiotics Crohn's Vs Site of Severity of Patient Goals of Ulcerative Disease Disease Factors treatment Colitis ACUTE SEVERE ULCERATIVE COLITIS **Truelove and Witt Criteria**: Severity Assessment Tool Medical Rescue Therapy SURGERY Avoided where possible, minimal resections Surgical treatment of IBD is reserved for serious cases which are non-responsive to medical treatment. Surgery is potentially curative for UC, and an estimated 20–25% of patients with ulcerative colitis will require colectomy. Ulcerative colitis may require surgery in the case of severe life-threatening complications of an acute attack, (such as perforation, toxic dilatation or massive haemorrhage), or in the case of chronic ill- health or risk of cancer. The high likelihood of recurrence makes surgery less attractive for Crohn’s disease although it may be necessary in patients with severe complications. Surgery does not cure Crohn’s disease, and it is estimated that the disease will recur within 5 years of surgery in 50% of patients, and after 10 years in 70–80% of patients. In some situations, such as localised symptomatic ileocaecal disease, surgery can be considered as a potential alternative to medical management. Specific indications for surgery include abscesses, complex perianal or internal fistulas that are unresponsive or insufficiently responsive to medical therapy, fibrostenotic strictures with symptoms of partial or complete bowel obstruction, high grade dysplasia, and cancer.  1 2 3 4 5 6 7 8 3 PLANNING MANAGEMENT  1 2 3 4 5 6 7 8 3 PLANNING MANAGEMENT 10 YEARS LATER THE ABOVE PATIENT PRESENTS WITH SEVERE CRAMPY ABDOMINAL PAIN – RIGHT SIDED On examination Distended abdomen Bowel sounds – initially ↑ now ↓ No flatus passed in 24 hours Abdomen soft INTESTINAL OBSTRUCTION Differential: Benign stricture Vs malignant neoplasm  WHY DO YOU GET STRICTURE IN CROHN’S DISEASE? Crohn’s disease causes transmural inflammation This heals by  Fibrosis – scarring of the bowel narrowing  Stricture – causes obstruction PARTIAL COLECTOMY, RIGHT SIDE COMPLICATIONS OF PARTIAL COLECTOMY Acute: Anastamotic leak Watery stool– lack of fluid absorption, high output stoma, dehydration, electrolyte disturbances. Ileocaecal valve important role in reducing transit time. Recurrence of disease at sites of anastomosis Terminal ileum resection – B12 deficiency – Bile Salts, steatorrhoea TYPES OF ANAEMIA - CROHN’S DISEASE B12 deficiency Folate deficiency Iron deficiency Due to Inadequate intake / insufficient absorption Or blood loss INVESTIGATIONS FOR ANAEMIA Anaemia is diagnosed on an FBC  Red blood cell size / Mean corpuscular volume (MCV) Microcytic Normocytic Macrocytic Iron deficiency B12/Folate deficiency RBC count, Hb, MCHC (mean corpuscular Hb conc.)  MCHC is reduced (‘hypochromic’) in microcytic anaemia and normochromic in macrocytic anaemia Blood film Diagnosis: B12 deficiency due to Terminal Ileitis LEARNING OUTCOME 8 & 9 State the complications of IBD Describe the gross and microscopic appearance of ulcerative colitis and Crohn’s disease - Pathology  COMPLICATIONS OF CROHN'S DISEASE Intestinal complications of Crohn's disease: Strictures Fistulas, sinus tracts Abscesses Perforation Toxic megacolon The cause for the obstruction in this patient may be a stricture related to fibrosis from chronic IBD COMPLICATIONS OF CROHN'S DISEASE (CONTINUED) Extra intestinal manifestations of Crohn's disease Eyes Skin  Uveitis  Erythema nodosum  Episcleritis  Pyoderma gangrenosum Mouth  Stomatitis Joints  Aphthous ulcers  Spondylitis Liver / biliary tract  Sacroiliitis  Steatosis  Peripheral arthritis  Sclerosing cholangitis Anaemias Kidneys  Fe, B12, Folate  Stones  Hydronephrosis  Fistulae  Infections CHARACTERISTICS DIFFERENTIATING CROHN’S DISEASE AND ULCERATIVE COLITIS CROHN'S DISEASE ULCERATIVE COLITIS ADDITIONAL COMPLICATIONS Ulcerative Colitis Crohn's Sclerosing cholangitis Fe, B12, folate Iron deficiency anaemia deficiency Erythema nodosum Dysplasia Eye symptoms Dysplasia in UC Erythema nodosum COLORECTAL DYSPLASIA IN ULCERATIVE COLITIS Colorectal dysplasia in ulcerative colitis Patient with severe colitis more than 10 years  PLEASE POST ANY QUESTIONS YOU MAY HAVE ON THE DISCUSSION FORUM ON MOODLE THANK YOU REFERENCES/ FURTHER RESOURCES https://www.uptodate.com/contents/dermatologic-and-ocular-manifestations-of-inflammatory-bowel-disease?searc h=episcleritis%20IBD&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-arthritis-associated-with-inflammatory- bowel-disease-and-other-gastrointestinal-diseases?search=sacroiliits%20in %20ibd&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-prognosis-of-ulcerative-colitis-in-adults?s earch=ibd&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802492/