GI Grand Rounds
Johanna Chan, PGY-5 Fellow
Baylor College of Medicine
6/5/2014
Mentors: Dr. Kalpesh Patel
Dr. Prasun Jalal
No conflicts of interest
No 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% RA
Gen: NAD, AAOx4, well-appearing
HEENT: +slight scleral icterus, PERRL, EOMI, MMM, OP
clear
CV: RRR no m/r/g
Chest: CTAB no wheezes, slight crackles at bases
Abd: soft, nondistended, nontender, NABS, no
organomegaly
Ext: WWP, no clubbing, cyanosis, or edema
Neuro: oriented x4, conversational
Labs on admission
140
107
3.6
27
Total prot 8.4
Albumin 4.7
Total bili 1.4
Direct bili 1.0
Alk phos 401
ALT 330
AST 172
12
0.63
82
5.6
11.1
263
33.2
47% PMNs
37% lymphs
INR 1.0
LDH 139
MCV 87
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 intraabdominal pathology
Pathology
• Periportal lymph node, biopsy
• Benign lymph node with noncaseating
granulomas
• AFB stain negative for mycobacteria
• GMS stain negative for fungal organisms
Additional labs
CA 19-9 21
CA 125 9
CEA <0.5
AFP 4
IgG 1197
IgG4 4.1
IgM 140
Anti-smooth muscle Ab
<20
Alpha 1 AT 190
Ceruloplasmin 43
HIV (−)
Quantiferon TB (+)
PPD (+)
Blood cultures (−)
Urine culture (−)
Surgically biopsied lymph
node:
<1+ WBCs
No organisms
AFB smear negative
AFB culture negative at 42
days
Fungal smear negative
Fungal culture negative at 28
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
• 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 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 foreignborn 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.
Clinical features of ATB
• 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.
Clinical features of ATB
• 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
Clinical features of ATB
• 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.
Clinical features of ATB
•
•
•
•
•
•
•
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
• 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?
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 sensitive
Bolukbas 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
• 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?
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
References
Bolukbas 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/GuidelinesPatient_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: 452454.
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.
Questions or comments?