GI Grand Rounds Johanna Chan, PGY-5 Fellow Baylor College of Medicine 6/5/2014 Mentors: Dr. Kalpesh Patel Dr. Prasun Jalal

GI Grand Rounds

Johanna Chan, PGY-5 FellowBaylor College of Medicine6/5/2014

Mentors: Dr. Kalpesh Patel Dr. Prasun Jalal

No conflicts of interestNo financial disclosures

HPI• Reason for consult: jaundice, abdominal pain• 33yo healthy woman with hypothyroidism,

admitted with 1 week of subacute RUQ abdominal pain, N/V, jaundice, dark urine, and acholic stools

• Similar episode 2005, resolved spontaneously• Worse with food• Subjective fever, no chills, rigors, weight loss

PMHx:– Hypothyroid– No known prior liver

disease

Medications:

− Synthroid 75 mcg

PSHx: None

FamHx:– Mother: alive/well– Father: alive/well– No liver disease or

autoimmune disease

Allergies: NKDA

SocHx– No EtOH, IVDA, nasal

cocaine, blood transfusions, tattoos

– Never smoker– Physician, originally from

Bolivia– No recent needle

exposures, antibiotics, unusual food exposures

– Travel to California 1/2014, Bolivia 2012, Europe 2008

– One household cat

Physical Exam

T 98.2, BP 112/67, HR 78, RR 12, O2 sat 98% RAGen: NAD, AAOx4, well-appearingHEENT: +slight scleral icterus, PERRL, EOMI, MMM, OP clearCV: RRR no m/r/gChest: CTAB no wheezes, slight crackles at basesAbd: soft, nondistended, nontender, NABS, no organomegalyExt: WWP, no clubbing, cyanosis, or edemaNeuro: oriented x4, conversational

Labs on admission

MCV 8747% PMNs37% lymphs

140

3.6 27

107 12

0.6382 5.6

33.2

11.1263

INR 1.0LDH 139

Total prot 8.4Albumin 4.7Total bili 1.4Direct bili 1.0Alk phos 401ALT 330AST 172

Imaging

• CXR “normal” three years ago (exposed to TB previously as a medical student)

• RUQ U/S– Normal liver size 12.4 cm, normal echogenicity,

smooth contour– Normal spleen size 9 cm– Gallbladder sludge– No gallbladder wall thickening nor pericholecystic

fluid– CBD 9 mm, CHD 7 mm

Clinical course

• ERCP: smooth biliary stricture, CBD stent– Brushing: rare atypical cells; interpretation limited by

poor cellular preservation and low cellularity• EUS/biopsy of porta hepatis mass:– Extensively fragmented tissue containing granulomas

with focal necrosis– No diagnostic dysplasia or malignancy– Stains negative for bacterial or fungal organisms– Ziehl Neelsen stain negative for acid fast organisms

Next diagnostic steps?

Clinical course• Diagnostic laparoscopy, laparoscopic

cholecystectomy, and robotic periportal lymph node dissection and lymphadenectomy

• Evidence of chronic cholecystitis• Posterior to CBD, well-formed and

encapsulated periportal lymph node with granulomatous features

• No evidence of miliary TB nor other intra-abdominal pathology

Pathology• Periportal lymph node, biopsy• Benign lymph node with noncaseating

granulomas• AFB stain negative for mycobacteria• GMS stain negative for fungal organisms

Additional labsCA 19-9 21CA 125 9CEA <0.5AFP 4

IgG 1197IgG4 4.1IgM 140Anti-smooth muscle Ab <20Alpha 1 AT 190Ceruloplasmin 43

HIV (−)Quantiferon TB (+)PPD (+)Blood cultures (−)Urine culture (−)

Surgically biopsied lymph node:<1+ WBCsNo organismsAFB smear negativeAFB culture negative at 42 daysFungal smear negativeFungal culture negative at 28 days

Obstructive jaundice secondary to extrinsic biliary compression

Working diagnosis:Intra-abdominal tuberculosis in the immunocompetent patient

Clinical questions

• What are clinical features of abdominal tuberculosis (ATB)?

• What are diagnostic modalities and yield for abdominal tuberculosis?

• What are mechanisms for obstructive jaundice in abdominal tuberculosis?

Clinical questions




Clinical features of ATB

• 1985 to 1992 showed a resurgence of TB in the U.S., coincident with AIDS epidemic

• TB incidence in U.S. declining since 1992• Global prevalence of TB estimated at 32%;

WHO estimates > 2 billion people• Percentage of U.S. cases occurring in foreign-

born persons is increasing (53% in 2003)Centers for Disease Control and Prevention. Trends in tuberculosis – United States, 1998-2003. MMWR Morb Mortal Wkly Rep 2004; 53:2009-14.Dye C et al. WHO Global Surveillance and Monitoring Project. JAMA 1999; 282: 677-86.


• Extrapulmonary TB accounts for 15-20% of cases in low-HIV prevalence areas

• Of these, abdominal tuberculosis accounts for 11% - 16% in non-HIV patients, or 1-3% of the total TB

• Much higher frequency of extrapulmonary disease in HIV patients – up to 50-70%

International standards for tuberculosis care (WHO). 2006 Jan.Uygur-Bayramicli O et al. 2003 May; 9(5):1098-101.Wang HS et al. Int J Tuberc Lung Dis 1998; 2: 569-574.


• Primary infection from reactivation of a dormant focus acquired somewhere in the past

• Secondary disease: spread via swallowed sputum, ingestion of unpasteurized milk, or spread hematogenously or from an adjacent organ


• Prior to routine pasteurization of milk, abdominal tuberculosis was not uncommon in the UK.

• Between 1912 and 1937 some 65,000 people died of tuberculosis contracted from consuming milk in England and Wales alone.

Wilson, GS (1943), British Medical Journal 1 (4286): 261.

Author Year Country No. of patients

Mamo JP et al. 2013 UK 17

Tan KK et al. 2009 Singapore 57

Chen HL et al. 2009 Taiwan 21

Ramesh J et al. 2008 UK 86

Akinkuollie AA et al.

2008 Nigeria 47

Tarcoveanu E et al. 2007 Romania 22

Khan R et al. 2006 Pakistan 209

Bolukbas C et al. 2005 Turkey 88

Uzunkoy A et al. 2004 Turkey 11

Uygur-Bayramicli O et al.

2003 Turkey 31

Rai S et al. 2003 UK 36

Muneef et al. 2001 Saudi Arabia 46

Clinical features of ATB• Enteric, peritoneal, nodal, or solid visceral (liver, spleen,

pancreas, kidney)• Intestinal involvement (colon, TI) most common, ranges

from 40 – 75% of abdominal TB– Abdominal pain, bleeding, change in bowel habit, weight loss– Ulcerative or hypertrophic lesions, nodules, circumferential

thickening on colonoscopy• Tuberculous peritonitis– Greater risk in patients with HIV or cirrhosis– Ascites, abdominal pain, fever– SAAG < 1.1 g/dL, exudative, lymphocytic-predominant

Khan R et al. 2006 Oct 21;12 (39):6371-5.Riquelme A et al. J Clin Gastroenterol. 2006 Sep; 40(8): 705-10. Uygur-Bayramicli O et al. 2003 May;9(5):1098-101.


• Abdominal pain (28 – 90%)• Fever (5 – 64%)• Weight loss (5 – 60%)• Nausea and vomiting (30 – 40%)• Ascites (20 – 35%)• Diarrhea (10 – 17%)• Active pulmonary TB or prior pulmonary TB lesion (17 –

27%)• Anemia in 10 – 11 g/dL range• ESR elevated in 50 – 60 mm/H range

Clinical questions




Diagnosis of abdominal TB• DDx intra-abdominal malignancy, abdominal

lymphoma, inflammatory bowel disease (Crohn’s), hepatitis, chronic pancreatitis, PUD

• Anemia and elevated ESR/CRP are the most common laboratory findings

• Nonspecific clinical features, laboratory findings, variable radiographic findings

• Microbiologic yield specific, not sensitiveBolukbas C et al. BMC Gastroenterol 2005; 5:21.Khan R et al. 2006 Oct 21;12 (39):6371-5.Mamo JP et al. Q J Med 2013 Apr; 106(4):347-54.Rai S et al. J R Soc Med 2003; 96:586-8.

Diagnosis of abdominal TB• Constellation of clinical and radiographic features• Highest yield for surgically obtained specimen

(laparotomy/laparoscopy), followed by CT/US guided biopsy and endoscopy

• Many authors suggest therapeutic trial with antitubercular therapy

• However, cannot recommend routine empiric antitubercular therapy– May delay diagnosis of malignancy, lymphoma, Crohn’s, etc.– Adverse effects with hepatitis, drug interactions, etc. not

uncommon Khan R et al. 2006 Oct 21;12 (39):6371-5.Mamo JP et al. Q J Med 2013 Apr; 106(4):347-54.Rai S et al. J R Soc Med 2003; 96:586-8.

Diagnostic yield in abdominal TB• AFB smear from samples insensitive (yield 0% - 6%)• AFB culture insensitive (yield 7% in large series)• Nucleic acid amplification tests (NAAT, e.g. PCR)

insensitive (7.1%) and in meta-analysis, insensitive for extrapulmonary disease

• IFN gamma release assay (IGRA, e.g. Quant TB) tests usually negative; unclear role for diagnosis of active TB

• Supportive histology most helpful (>90% surgical specimen, 50-80% endoscopic specimen)Dinnes J et al. Health Technol Assess 2007; 11:1-196.

Khan R et al. 2006 Oct 21;12 (39):6371-5.Mamo JP et al. Q J Med 2013 Apr; 106(4):347-54.

Clinical questions




Case: obstructive jaundice due to TB

• TB of pancreas itself may cause pseudoneoplastic obstructive jaundice

• TB lymphadenitis may cause extrinsic CBD compression (smooth narrowing of CBD)

• Biliary TB itself may cause strictures, mimicking cholangiocarcinoma

• TB may cause retroperitoneal mass leading to biliary obstruction

Colovic R et al. World J Gastroenterol 2008; 14 (19): 3098-3100.

Take home points• Maintain a high index of suspicion, especially in

patients from TB-endemic countries• Obtain samples for AFB and mycobacterial

culture (laparotomy, laparoscopy, endoscopy)• Microbiology is specific but extremely

insensitive• Multidisciplinary approach including ID and

surgery• Empiric antitubercular treatment is not

routinely recommended

ReferencesBolukbas C et al. Clinical presentation of abdominal tuberculosis in HIV seronegative adults. BMC

Gastroenterol 2005; 5:21.Centers for Disease Control and Prevention. Trends in tuberculosis – United States, 1998-2003.

MMWR Morb Mortal Wkly Rep 2004; 53:2009-14.Colovic R et al. Tuberculous lymphadenitis as a cause of obstructive jaundice: a case report and

literature review. World J Gastroenterol 2008 May 21; 14 (19): 3098-3100.Dinnes J et al. A systematic review of rapid diagnostic tests for the detection of tuberculosis

infection. Health Technol Assess 2007; 11:1-196.Dye C et al. Consensus statement. Global burden of tuberculosis: estimated incidence,

prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999; 282: 677-86.

Kapoor VK. Abdominal tuberculosis: the Indian contribution. Indian J Gastroenterol 1998; 17: 141-147.

Khan R et al. Diagnostic dilemma of abdominal tuberculosis in non-HIV patients: an ongoing challenge for physicians. World J Gastroenterol. 2006 Oct 21;12 (39):6371-5.

International Standards for Tuberculosis Care (WHO). Endorsed by IDSA. Published January 2006. Accessed online 6/4/14 http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/International%20TB.pdf

http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/International%20TB.pdf

http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/International%20TB.pdf

References (continued)Mamo JP et al. Abdominal tuberculosis: a retrospective review of cases presenting to a UK district

hospital. Q J Med 2013 Apr; 106(4):347-54.Misra SP et al. Colonic tuberculosis: clinical features, endoscopic appearance, and management. J

Gastroenterol Hepatol 1999; 14: 723-729.Muneef MA et al. Tuberculosis in the belly: a review of forty-six cases involving the gastrointestinal tract and

peritoneum. Scand J Gastroenterol 2001; 36: 528-532.Murphy TF et al. Biliary tract obstruction due to tuberculous adenitis. Am J Med 1980; 68: 452-454.Rai S et al. Diagnosis of abdominal tuberculosis: the importance of laparoscopy. J R Soc Med 2003; 96:586-8.Riquelme A et al. Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous

peritonitis: a meta-analysis. J Clin Gastroenterol. 2006 Sep; 40(8): 705-10. Singhal A et al. Abdominal tuberculosis in Bradford, UK: 1992-2002. Eur J Gastroentrol Hepatol 2005; 17:

967-971. Sheer TA et al. Gastrointestinal tuberculosis. Curr Gastroenterol Rep 2003; 5:273-278. Sinan T et al. CT features in abdominal tuberculosis: 20 years experience. BMC Medical Imaging 2002; 2: 3-

16.Uygur-Bayramicli O et al. A clinical dilemma: abdominal tuberculosis. 2003 May;9(5):1098-101.Uzunkoy A et al. Diagnosis of abdominal tuberculosis: experience from 11 cases and review of the literature.

2004 Dec 15; 10(24):3647-9.Wang HS et al. The changing pattern of intestinal tuberculosis: 30 years’ experience. Int J Tuberc Lung Dis

1998; 2: 569-574.Wilson, G. S. (1943), “The Pasteurization of Milk,” British Medical Journal 1 (4286): 261.

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GI Grand Rounds Johanna Chan, PGY-5 Fellow Baylor College of Medicine 6/5/2014 Mentors: Dr. Kalpesh Patel Dr. Prasun Jalal