1. Case Presentation Ezana M. Azene

2. HPI – Day 1 35 y/o immigrant from Guatemala living in U.S. for past 3 years CC: 3 months burning left-sided abdominal pain radiating to epigastrium and back PresentAbsent Decreased appetite, 20 lb wt loss over 2-3 months Subjective fever, chills, night sweats, incarceration, tattoos, blood transfusions, IV drug use Watery diarrhea for 2 monthsSexual activity (Married and sexually abstinent since leaving Guatemala) Crowded living conditions (5 other immigrants) SOB, headache, dysuria, skin rash, myalgias, arthralgias 1-2 weeks cough, occasionally productiveHemoptysis

3. Physical Exam – Day 1 Febrile Abdomen soft with moderate TTP diffusely, mild guarding without rebound, normal bowel sounds, possible splenomegaly Remainder of exam normal

4. Relevant Initial Lab-work – Day 1 Hct: 26↓, WBCC: 3.3 ↓ (4% ↓ lymphocytes) Alb: 1.7 ↓, TP: 7.3 (gamma gap = 5.6↑) AlkPhos: 727 ↑ (with GGT ↑), AST 116 ↑, ALT 81 ↑ Lipase: normal

5. Initial CE CT – Day 1 2 cm MIP

6. Initial CE CT – Day 1

9. CT report – Day 1 “… very suggestive of mycobacterial … infection. Extensive fat stranding makes lymphoma or other malignancy less likely.”

10. Admitting Plan IV fluids HIV serology TB w/u (including sputum AFB and sputum/blood culture) Negative pressure isolation and droplet precautions

11. Abdominal U/S – Day 2 SpleenOmentum Increased omental echogenicity

12. U/S Report “Mass-like thickening of the omentum. Findings worrisome for TB peritonitis”

13. Hospital Course HIV positive (CD4 ~ 60) – Day 2 ID consult – Day 2 –DDx: Lymphoma > disseminated histoplasmosis > typhoid fever > TB > septic emboli –“Would continue off antimicrobial therapy” –Recommended tissue biopsy Hematology consult – Day 4 –DDx: Lymphoma > TB Sputum AFB negative Culture negative

14. Hospital Course Abdominal paracentesis – Day 5 –Reactive cells, no malignancy –AFB negative –Cultures pending Respiratory isolation stopped – Day 5 or 6 Bone marrow biopsy – Day 6 –Negative Echocardiogram – Day 10 –Normal Sputum AFB negative Culture negative

15. Hospital Course Unstable, ICU transfer – Day 10 –Non-con CT: calcified perihepatic lymph node (missed on CE CT) Liver core biopsy – Day 11 –Granuloma with rare filamentous AFB TB Rx started – Day 11 (I think…) Actinomyces? TB? Nocardia?

16. Hospital Course CT guided omental biopsy – Day 12 –Benign fibroadipose tissue with focal granuloma Patient rapidly improved and discharged home – Day 19

17. Post-Hospital Course Initial induced sputum cultures positive for TB 4 days after discharge Initial blood cultures positive for TB 1 day after discharge Liver biopsy culture positive for TB 4 days after discharge Omental biopsy culture positive for TB 6 days after discharge Ascites was never positive for TB or AFB

18. Current Patient Status Not fully compliant with D.O.T.S. and HAART –May need incarceration

19. TB Peritonitis History Mechanism of Spread Frequency Mortality Classic Types Diagnosis –Biochemical –Microbiological –Imaging Suggestive features Differential –Necrotic abdominal lymph nodes –Omental infiltration –Splenic hypodense nodules

20. Google Timeline “Tuberculous peritonitis” OR “Peritoneal tuberculosis” OR “abdominal tuberculosis” The earliest concrete evidence of the presence of abdominal tuberculosis was the autopsy report of Louis XIII in 1643 (although Hippocrates said, “Pthisical persons die if diarrhoea sets in”) -30 year war against Hapsburg Dynasty -Weak, petulant, vain ruler -Supporting role in Dumas’ “The Three Musketeers”

21. Google Timeline “Tuberculous peritonitis” OR “Peritoneal tuberculosis” OR “abdominal tuberculosis” 1882: Robert Koch describes his discovery of the Mycobacterium tuberculosis organism. "If the importance of a disease for mankind is measured by the number of fatalities it causes, then tuberculosis must be considered much more important than those most feared infectious diseases, plague, cholera and the like. One in seven of all human beings dies from tuberculosis. If one only considers the productive middle- age groups, tuberculosis carries away one-third, and often more." 1905 Nobel Prize

22. Google Timeline “Tuberculous peritonitis” OR “Peritoneal tuberculosis” OR “abdominal tuberculosis” 1932: Gastroenterologist Burrill Bernard Crohn, 1 st American to describe “Terminal ileitis: a new clinical entity”. Many cases of TB enteritis/peritonitis re-classified as Chron Disease. 1917: Mandatory milk pasteurization begins in United States WWII

23. Google Timeline “Tuberculous peritonitis” OR “Peritoneal tuberculosis” OR “abdominal tuberculosis” 1943: Albert Schatz and Selman Waksman discover Streptomycin at Rutgers University 1952 Nobel Prize

24. Google Timeline “Tuberculous peritonitis” OR “Peritoneal tuberculosis” OR “abdominal tuberculosis” 1980s: HIV/AIDS

25. We used to know this stuff! Treves, Frederick. “The treatment of tuberculous peritonitis”. Ann. Surg. 1894. -Sir Frederick Treves -Eminent Victorian surgeon -Physician to Joseph Merrick, The Elephant Man -Performed 1 st appendectomy (1888) in England (Savedlife of King Edward VII in 1901) -Founder of British Red Cross -Biographer of Blackbeard the Pirate

26. We used to know this stuff! Treves, F. “The treatment of tuberculous peritonitis”. Ann. Surg. 1894.

27. We used to know this stuff! Treves, F. “The treatment of tuberculous peritonitis”. Ann. Surg. 1894.

28. We used to know this stuff Treves, F. “The treatment of tuberculous peritonitis”. Ann. Surg. 1894.

29. Mechanism of Spread to Peritoneum, Omentum, and Mesentery Infection of GI mucosa by contaminated milk or swallowed sputum followed by transmural spread Direct hematogenous spread Lymphatic spread with direct extension –e.g. from ruptured necrotic lymph nodes Eur Radiol (2004) 14:E103–E115 The Internet Journal of Infectious Diseases. 2010 Volume 8 Number 2 Ascites Tiny peritoneal nodules (appear confluent on CT) Omental thickening Through the Laparoscope

30. Frequency of TBP TB peritonitis occurs in < 4% of TB patients However, in developing countries, up to … –30% of non-pulmonary TB involves TB peritonitis –20% of all ascites is due to TB peritonitis Increased risk with alcoholism, cirrhosis, renal failure, diabetes mellitus, malignancy, intravenous drug abuse, steroid therapy, and AIDS. Singapore Med J 2008; 49(6) : 488 Eur Radiol (2004) 14:E103–E115

31. Mortality of TBP 15-60% in post-antibiotic era –Higher when hepatic cirrhosis present “The high mortality for tuberculous peritonitis is explained, at least in part, by its highly variable and often nonspecific clinical presentation and the practical difficulties in establishing an early bacteriologic diagnosis.” EARLY INITIATION OF THERAPY REDUCES MORTALITY Chow et al. Clinical Infectious Diseases 2002; 35:409–13

32. Classic Types of TBP (basically useless) Wet type (90%) –Free or loculated ascites Fibrotic fixed type occurs (60%) –Omental masses and matted loops of bowel and mesentery Dry or plastic type (10%) –Caseous lymph nodes, fibrous peritoneal reaction, and dense adhesions Our case was Wet + Dry Journal of Clinical Imaging 28 (2004) 340–343

33. Fibrotic Fixed, “Abdominal Cocoon” Wet type Am. J. Trop. Med. Hyg., 84(1), 2011, pp. 1–2

34. Biochemical Diagnosis of TBP Adenosine Deaminase elevated in ascites –In one meta-analysis, ADA levels showed high sensitivity (100%) and specificity (97%) CA 125 may be elevated (mimicking ovarian CA) J Clin Gastroenterol Volume 40, Number 8, September 2006

35. Microbiological Diagnosis of TBP Ascites smear, PCR and culture have extremely low sensitivity (<5% in most studies) Lymphocytic exudate usually present Tissue biopsy usually needed –Omentum or lymph nodes –Granulomas (usually caseating) –Not always smear positive –High sensitivity with liquid culture J Clin Gastroenterol Volume 40, Number 8, September 2006

36. CT Appearance Suggestive of TBP Smooth, mild, non-nodular peritoneal thickening with pronounced enhancement “Smudged” appearance of omentum (extensive stranding) Presence of mesenteric macronodules (> 5 mm) Splenic hypodensities and splenomegaly Low density and/or calcified lymph nodes Ascites may be higher density than water Journal of Computer Assisted Tomography Volume 20(2), March/April 1996, pp 269-272 Eur Radiol (2004) 14:E103–E115 Singapore Med J 2008; 49(6) : 488

37. Ha et al. AJR. 167. 1996 TBP Journal of Computer Assisted Tomography Volume 20(2), March/April 1996, pp 269- 272

38. Journal of Computer Assisted Tomography Volume 20(2), March/April 1996, pp 269-272 Carcinomatosis

39. Ha et al. AJR. 167. 1996 Carcinomatosis

40. Singapore Med J 2008; 49(6) : 488 TBP: TypicalTBP: Atypical

41. Ha et al. AJR. 167. 1996 TBP Singapore Med J 2008; 49(6) : 488

42. Journal of Computer Assisted Tomography Volume 20(2), March/April 1996, pp 269-272 TBP

43. US Appearance of TBP Increased omental echogenicity Diffuse, hypoechoic peritoneal thickening (2-6 mm) Echogenic fibrous strands creating locculations of ascites Most useful for guiding biopsy

44. DDx Omental and peritoneal findings –Malignancy (carcinomatosis (esp. ovaian), mesothelioma, lymphoma) –Non-TB peritonitis Hypodense lymph nodes –Whipple disease –Typhoid fever –Celiac Disease –Burkitt/Burkitt-type lymphoma –Treated lymphoma and necrotic metastases Splenic Hypodensities –Lymphoma –Sarcoidosis –Non-TB microabscesses –Lymphatic malformations –Vascular anomalies

45. Summary TB peritonitis carries high mortality and requires rapid treatment Image-guided biopsy (omental, lymph node) is best chance for definitive diagnosis –Usually no need for surgical biopsy Imaging, especially CT, may be 1 st clue to diagnosis –If characteristic findings are present in appropriate epidemiological setting… TREAT, then stop treatment if you’re wrong

46. Summary Think of TB Peritonitis if 2 or more… –Extensive omental and mesenteric fat stranding –Hypodense abdominal lymph nodes –Splenic hypodensities –Higher than normal density ascites (not like blood, though) –Smooth peritoneal thickening –Moderate peritoneal enhancement