Extraintestinal Manifestations OF IBD Inflammatory Bowel Disease : A complete overview

Extraintestinal Manifestations OF IBD Inflammtory Bowel Disease

Arthritis, Uveitis, Scleritis, Pyoderma gangrenosum, Hepatic involvement, Ulcers, thrombosis, amyloidosis, bone, gall stones, Ulcerative, Crohns

1. EXTRA INTESTINAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE Guide : Dr Chandrashekar K (Associate Professor) Student : Dr Chetan K G

2. INTRODUCTION CLINICAL FEATURES OF IBD RADIOLOGICAL SIGNS EXTRAINTESTINAL MANIFESTATIONS CASE SCENARIOS

3. IBD Clinically, inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestines that is marked by remission and relapses due to inappropriate mucosal immune response .

4. Types of IBD TYPICAL IBD : (2 Major Types): Ulcerative Colitis (Colitis Ulcerosa ) Crohn’s Disease (Regional Enteritis) ATYPICAL IBD: Lymphocytic Colitis Collagenous Colitis Ischaemic Colitis Diversion Colitis Indeterminate Colitis Bachet’s Disease

5. Symptoms suggestive of IBD include Watery stools, blood or mucus in the stool Diarrhoea - persisting for more than 4 weeks Crampy abdominal pain, Nocturnal defecation Fever. Weight loss is significant. Anal fissures, anal fistulae, frank bleeding per rectum Abdominal masses can occur Symptoms are generally recurrent.

6. Ulcerative Colitis with lead pipe colon.

7. Extra Intestinal manifestations (EIM) The pathogenesis of EIM in IBD is not well understood. Diseased gastrointestinal mucosa may trigger immune responses at the extraintestinal site due to shared epitopes . E.g.: intestinal bacteria and the synovia : bacteria that are translocated across the leaky intestinal barrier trigger an adaptive immune response that finally is unable to discriminate between bacterial epitopes and epitopes of joints or the skin.

8. Triggers of the autoimmune responses in certain organs seem to be influenced by genetic factors. EIM in patients with CD are more frequently observed in patients with HLA-A2, HLA-DR1, and HLA-DQw5 EIM in patients with UC are more likely to appear when the HLA-DR103 genotype is present.

9. HLA-B8/DR3 is associated with an increased risk of PSC in UC. HLA-DRB1-0103, HLA-B-27, and HLA-B-58 are associated with EIM of joints, the skin, and eyes, respectively, in patients with IBD. HLA-B*27 itself does not seem to be associated with IBD, but HLA-B*27 shows a strong association with the development of ankylosing spondylitis , as 50% to 90% of patients with IBD are positive for this marker.

10. EXTRA INTESTINAL MANIFESTATIONS

11. EIM

12. EIM

13. EIM

14. DERMATOLOGICAL MANIFESTATIONS - Erythema nodosum 15% in CD & 10% in UC Skin lesions develop after the onset of bowel symptoms Concomitant active peripheral arthritis EN are hot, red, tender nodules measuring 1–5 cm in diameter and are found on the anterior surface of the lower legs, ankles, calves, thighs, and arms

15. Pyoderma gangrenosum 1–12% of UC patients and less commonly in Crohn’s colitis May occur years before the onset of bowel symptoms Run a course independent of the bowel disease Respond poorly to colectomy Usually associated with severe disease

16. Lesion of PD Begins as a pustule and then spreads concentrically Lesions then ulcerate, with violaceous edges surrounded by a margin of erythema Centrally, they contain necrotic tissue with blood and exudates Lesions may be single or multiple and grow as large as 30 cm

17. Other dermatologic manifestations Pyoderma Vegetans Pyostomatitis Vegetans Sweet Syndrome Psoriasis Perianal Skin Tag Aphthous Stomatitis

18. RHEUMATOLOGIC - ARTHRITIS Arthritis Develops In 15–20% Of IBD Patients Common In CD > UC Worsens With Exacerbations Of Bowel Activity Asymmetric, Polyarticular , And Migratory And Most Often Affects Large Joints Of The Upper And Lower Extremities Colectomy frequently Cures The Arthritis

19. Ankylosing spondylitis 10% Of IBD patients Common in CD > UC 2/3 rd patients are HLA-B27 antigen positive Activity is not related to bowel activity

20. SACROILITIS Symmetrical (both joints) Occurs equally in UC and CD Does not correlate with bowel activity

21. Others are Hypertrophic Osteoarthropathy Pelvic/Femoral Osteomyelitis Relapsing Polychondritis

22. RELAPSING POLYCHONDRITIS

23. OCULAR Seen in 1-10% of cases Conjunctivitis Anterior uveitis Iritis Episcleritis (3-4% CD > UC) Uveitis : found during periods of remission and develop in patients following bowel resection.

24. HEPATOBILIARY Hepatic steatosis : 50% cases Hepatomegaly is found on examination Cholelithiasis is seen in 10-35% after ileal resection or ileitis Primary Sclerosing Cholangitis Gall bladder polyps

25. Primary sclerosing cholangitis Intrahepatic and extrahepatic bile duct inflammation and fibrosis Biliary cirrhosis and hepatic failure ~5% of patients with UC have PSC , UC > CD IBD and PSC are commonly p-ANCA positive Both ERCP and MRCP demonstrate multiple bile duct strictures alternating with relatively normal segments

26. Gallbladder polyps in patients with PSC have a high incidence of malignancy and cholecystectomy is recommended, even if a mass lesion is less than 1 cm in diameter Patients with symptomatic disease develop cirrhosis and liver failure over 5–10 years\ IBD and PSC are at increased risk of colon cancer and should be surveyed yearly by colonoscopy and biopsy

27. Biliary Lithiasis

28. UROLOGY Calculi Ureteral obstruction Ileal -bladder fistulas N ephrolithiasis (10–20%) occurs in patients with CD following small bowel resection Calcium oxalate stones develop secondary to hyperoxaluria , which results from increased absorption of dietary oxalate

29. In patients with ileal dysfunction, nonabsorbed fatty acids bind calcium and leave oxalate unbound. The unbound oxalate is then delivered to the colon, where it is readily absorbed, especially in the presence of inflammation

30. THROMBOEMBOLIC DISORDERS Increased risk of both venous and arterial thrombosis even if the disease is not active Abnormalities Of The Platelet-endothelial Interaction, Hyperhomocysteinemia , Alterations In The Coagulation Cascade, Impaired Fibrinolysis ,

31. Involvement Of Tissue Factor-bearing Microvesicles , Disruption Of The Normal Coagulation System By Autoantibodies Genetic Predisposition A spectrum of vasculitides involving small, medium, and large vessels has also been observed.

32. METABOLIC BONE DISORDERS Low bone mass occurs in 14–42% of IBD patients An increased incidence of hip, spine, wrist, and rib fractures has been noted: 36% in CD and 45% in UC (spine and hip are highest with age >60years)

33. Up to 20% of bone mass can be lost per year with chronic glucocorticoid use G lucocorticoids , methotrexate (MTX), and total parenteral nutrition (TPN) further increases the risk

34. Osteonecrosis is characterized by death of osteocytes and adipocytes and eventual bone collapse The pain is aggravated by motion and swelling of the joints. It affects the hips more often than knees and shoulders

35. Osteonecrosis diagnosis is made by bone scan or MRI Treatment consists of Pain Control Cord Decompression Osteotomy Joint Replacement.

36. CARDIOPULMONARY Endocarditis Myocarditis Pleuropericarditis Interstitial Lung Disease

37. OTHER MANIFESTATIONS Secondary or reactive amyloidosis causing diarrhea, constipation, and renal failure. The renal disease can be successfully treated with colchicine .

38. Pancreatitis is a rare extraintestinal manifestation of IBD It results from duodenal fistulas, ampullary CD, gallstones, PSC Drugs such as 6-mercaptopurine, azathioprine ,, 5-ASA agents can also lead to the pancreatitis Autoimmune pancreatitis

39. CASE SCENARIO CASE SERIES ON EXTRA INTESTINAL MANIFESTATION OF IBD

40. References Harrisons principles of internal medicine, 20 th Edition Bailey and Love’s short practice of surgery 27 th edition API text book of medicine, 9 th edition Sherlock’s disease of the liver and biliary system Beyond the Bowel: Extraintestinal Manifestations of Inflammatory Bowel Disease, Jeffery D et al., Multisystem radiology, May 26 2017, Volume 26, no4 Extraintestinal Manifestations of Inflammatory Bowel Disease, Stephan R. Vavricka et al., Inflamm Bowel Dis Volume 21, Number 8, August 2015