1. A 17- Year- Old Boy with Biliary Obstruction CC

2. HPI- 17 months prior to admission to MGH Symptoms: Bloody diarrhea admission to a hospital  what exams to do?

3. LAB • Serum aspartate aminotransferase level: 75 U/l • Test for Clostridium difficile: positive  had not taken antibiotics before!  management?

4. MANAGEMENT One month course of metronidazole  patient feels well

5. Several weeks prior to admission to MGH Symptoms: • constant crampy, nonradiatingpain in the epigastrium, right upper quadrant, periumbilical area, • pain exacerbates by eating, accompanied by nausea • intermittent loose stools without frequent or voluminous diarrhea • temp. rises intermittently to 38.3 °C

6. Five days prior to admission Symptoms: • leftsided pleuritic chest pain • dry cough admission to a hospital exams?

7. BLOOD CHEMICAL AND ENZYME VALUES Variable 5d. Before admission Protein (g/dl) Total Albumin 3.1 Globulin Bilirubin (mg/dl) Total 2 Conjugated 1 Alanine aminotransferase (U/l) 144 Aspartate aminotransferase (U/l) 74 Alkaline phosphatase (U/l) 601 LAB • Leucocytosis with a leftward shift

8. CXR Suggesting presence of pneumonia of the right lower lobe

9. Abdominal US No abnormalities

10. Progress of the patient Various pain medications are ineffective.  transfer to MGH  what to do?

11. PMH No informations

12. Immunizations His immunizations are up to date and include viral hepatitis B vaccination.

13. FH No family history of inflammatory bowel disease or rheumatic disorders

14. SH • 17- year- old student • No history of alcohol or illicit drugs

15. ROS • Constitutional: lost 3kg in weight during the preceding two weeks • GI:stools of normal color • GU:urine darker than usual

16. Physical Examination VS: Temp.: 37.8 °C Pulse : 85 BP : 120/55 mm Hg Resp. : 20

17. Physical Examination • Eyes: mild scleral icterus • Chest: supsternal pain • Lungs: clear • Abdomen: • soft with slight tenderness in the right upper quadrant • no hepatomegaly admission testings

18. LAB (1)

19. HEMATOLOGIC LABORATORY VALUES Variable On admission Hematocrit (%) 36.8 White-cell count (per mm3) 16,000 Differential count (%) Neutrophils 86 Lymphocytes 7 Monocytes 5 Eosinophils 2 Platelet count (per mm3) 504,000 Prothrombin time (sec) 12.9 Partial-thromboplastin time (sec) 35.3 LAB (2)

20. LAB (3)

21. Assessment The patient is a 17-year-old boy,who suffers from epigastrical pain and intermittently from diarrhea (even bloody in the past). Moreover there is evidence of biliary obstruction.

22. CXR Bilateral prominence of the interstitial markings

23. Adominal US • Liver of normal texture • Inrahepatic ducts and the common bile duct of normal diameter • Partially collapsed gallbladder • Normal pancreas

24. Stool • Stool specimen positive (+) for occult blood • Microscopical examination: • excessive number of undigested muscle fibers and abundant yeasts • no protozoa or helminthic ova • No C. difficile toxin • No enteric pathogens

25. Urine • Positive (++) for bile • Minimally positive for urobilinogen • Normal sediment  management?

26. Management Ranitidine, clarithromycin and acetaminophen are given

27. Progress of the patient Temp. rises to 39.7 °C

28. 2nd hospital day • Temp. does not exceed 39°C • Abdominal pain ceases exams?

29. Physical Examination Unchanged  additional testings

30. LAB

31. Abdominal US No abnormalities

32. CT CT of the abdomen and pelvis after oral and iv. administration of contrast material  no abnormalities

33. Intestinal disease-differential diagnosis • Infectious disease • Celiac sprue • Inflammatory bowel disease

34. Infectious disease The patient´s clinical course and the result of the limited testing that was performed make it very improbable that the illness has an infectious cause.

35. Celiac sprue • Unlikely diagnosis in this case because the illness generally developes in adults or in children younger than this patient. • An acute onset of marked upper gastrointestinal symptoms is atypical of celiac disease.

36. Inflammatory bowel disease • The initial signs, symptoms and laboratory findings that suggest inflammatory bowel disease include diarrhea, fever, weight loss, leukocytosis, thrombocytosis and occult blood in the stool. • Upper gastrointestinal involvement is more common in children with this disease than in adults.

37. Liver disease-differential diagnosis • Primary sclerosing cholangitis • Autoimmune hepatitis

38. Liver disease-differential diagnosis • Primary sclerosing cholangitis: can involve the extrahepatic ducts, the intrahepatic or both • Autoimmune hepatitis: characteristically involves the hepatic parenchyma =>both are common in inflammatory bowel disease

39. Exams • Evaluation of autoimmune markers • Liver biopsy • Endoscopic retrograde cholangiopancreatography

40. Autoimmune markers

41. Liver biopsy The expanded portal tract (arrows) contains a duct surrounded by edema (arrowheads)

42. Liver biopsy The pericuctal edema (arrow) results in an onionskin appearance. There is no inflammation at the interfaces of the portal tracts and hepatic lobules.

43. Pathological discussion • Preservation of the hepatic architecture • Expansion of the portal tracts, which are rounded and edematous • Within the portal tracts almost all the interlobular bile ducts are acutely inflamed • No inflammation at the interfaces of the portal tracts and hepatic lobules • A singel so-called bile infarct

44. ERCP Specimen of the Gastric Fundus. There is a granulomatous reaction around a damaged gastric gland (arrows).

45. ERCP Specimen of the Duodenum. The central duct is acutely inflamed and ruptured and is surrounded by acute and chronic inflammation.

46. Pathological discussion • No evidence of extrahepatic bile-duct obstruction • Severe inflammation and an epithelioid granuloma in the gastric wall • Patchy, superficial inflammation and deep acute and chronic inflammation

47. Diagnosis Primary sclerosing cholangitis associated with Crohn`s disease.

48. Treatment • Treatment with prednisone and ursodiol.Later on p. is replaced with mesalamine. • Patient get`s introduced to the idea that he might be a candidate for liver transplantation (p.s.c.:risk for bile-duct-cancer).

49. Addendum • 36 months later the aminotransferase levels are still slightly and the y-glutamyltransferase level is moderately elevated. • A ERCP showes no change in the degree of narrowing of the intrahepatic ducts.