DIAGNOSIS OF ABDOMINAL TUBERCULOSIS : ROLE OF

IMAGING

• Published in journal, indian academy of clinical medicine

• Vol. 2, no.3 july - september 2001

• By Rita sood

Additional professor

Deparment of medicine

AIIMS, NEW DELHI.

INTRODUCTION

• Tuberculosis has been declared a global emergency by the WHO.

• The prevalence of extra-pulmonary tuberculosis seems to be rising, due to increasing prevalence AIDS.

• In patients with extrapulmonary tuberculosis, abdomen is involved in 11% of patients

PATHOLOGICAL SPECTRUM

• The involvement of the GIT is seen in 65%-78% of patients of abdominal tuberculosis.

• common sites are the terminal ileum and the ileocaecal region, followed by colon and jejunum.

• Rarely stomach, duodenum, and oesophagus.

PATHOLOGICAL SPECTRUM

• The intestinal lesions produced by tuberculosis are of three types -

ulcerative

hypertrophic

stricturous.

• A combination of the three morphological forms of lesions i.e., ulcero-constrictive or ulcerohypertrophic may occur.

PATHOLOGICAL SPECTRUM

• GI tuberculosis have mostly associated nodal and peritoneal involvement.

1. Peritoneal involvement - adhesive or ascitic.

2. nodal involvement - commonly mesenteric or retroperitoneal shows caseation or calcification

• Hepatosplenic tuberculosis is common as a part of disseminated and miliary tuberculosis.

CLINICAL SPECTRUM

• Most commonly in young adults can present at any age.

• Modes of presentation can vary from

acute,

acute on-chronic

chronic,

incidental finding on laparotomy for unrelated causes.

CLINICAL SPECTRUM

• Chronic diarrhoea and malabsorption -Ulcerative type

• Rarely rectal bleeding - colonic tuberculosis.

• subacute intestinal obstruction - Stricturoustype in the form of obstipation, vomiting, abdominal distension, and colicky abdominal pain.

CLINICAL SPECTRUM

• Ano-rectal tuberculosis can present as strictures and multiple fistula-in-ano.

• caecum and large intestine, lesions are usually hypertrophic -obstruction or as abdominal lump.

• Gastroduodenal tuberculosis may present as peptic ulcer with or without gastric outlet obstruction or perforation and may mimic malignancy.

CLINICAL SPECTRUM

• Focal lesions in the liver and spleen are generally seen as a part of disseminated tuberculosis.

• Tuberculosis at unusual sites like pancreas, and oesophagus, mimics malignancy.

• Peritoneal tuberculosis often presents as abdominal distension and ascites or sometimes as a soft cystic lump due to loculated ascites.

CLINICAL SPECTRUM

• LN involvement - lump in central abdomen, or as vague abdominal pain.

• constitutional symptoms like lowgrade fever, malaise, night sweats, anaemia, and weight loss are present in about one-third of patients

DIFFERENTIAL DIAGNOSIS

• Abdominal tuberculosis can mimic a large number of medical and surgical conditions because of wide clinical spectrum.

• Hypertrophic form mimic malignant neoplasms such as lymphoma or carcinoma.

• ulcero-hypertrophic form - inflammatory bowel disease.

DIFFERENTIAL DIAGNOSIS

• Nodal form may closely mimic lymphomas.

• Ascitic form can be difficult to distinguish from malignant peritoneal disease and sometimes ascites due to chronic liver disease.

• However, a high index of suspicion needs to be maintained for an early diagnosis and timely treatment.

INVESTIGATIONS

• Haematological examination may show presence of anaemia, hypoalbuminaemia and an elevated ESR.

• Mantoux Test may be positive but is of not much value as it does not differentiate between an active and inactive disease.

Mantoux Test

• Induration of 10–14 mm in children <5 years of age strongly indicates active infection.

• Patients with an induration >14 mm are four times more likely to have an active disease than those with the range of 10–14 mm.

(Paediatric Surgery CHAPTER 18 Tuberculosis Shilpa Sharma Devendra K. Gupta)

INVESTIGATIONS

• Serological tests like soluble antigen fluorescent antibody (SAFA) and enzyme-linked immunosorbent assay (ELISA) are not sensitive and are non-specific and can only suggest a probable diagnosis.

Enzyme-Linked Immunoassay Test

• The test basically detects the presenceof interferon gamma release protein (IFN-g) from the blood of sensitised patients when incubated with the early secretory antigenic target-6 (ESAT6) and culture filtrate protein 10 (CFP10) peptides.

• The test is as sensitive as, and more specific than, the tuberculin skin test.

• It is recommended as a screening tool for diagnosing disease as well as infection.

(Paediatric Surgery CHAPTER 18 Tuberculosis ShilpaSharma Devendra K. Gupta)

INVESTIGATIONS

• In patient with ascites, peritoneal fluid analysis shows- straw coloured

1. proteins more than 30g/l,

2. cells more than 1,000/cu.mm (mostly lymphocytes),

3. ascitic/blood glucose ratio of less than 0.96, and

4. adenosine deaminase (ADA) levels of more than 33 U/l.

INVESTIGATIONS

• Adenosine deaminase (ADA) is increased in tuberculous ascitic fluid due to the stimulation of T-cells by mycobacterial antigens.

• In coinfection with HIV, the ADA values can be normal or low.

• High interferon levels in tubercular ascitis have been found to be useful diagnostically.

• Combining both ADA and interferon estimations may further increase the sensitivity and the specificity.

INVESTIGATIONS

• AFB are rarely seen on smear but may be cultured from the ascitic fluid. The yield may be increased centrifugation of a litre of fluid.

• Confirmation of the diagnosis of tuberculosis at any site is ideally established by

1. demonstrating AFB on smear or

2. mycobacterial culture from the tissue or by

3. demonstrating caseating granulomas at histopathology.

RADIOLOGICAL INVESTIGATIONS

• An erect radiograph is also invaluable at the time of abdominal pain in demonstrating

dilated jejunal and ileal loops with multiple air fluid levels, with an absence of gas in the colon and fixed bowel loop in cases of obstruction,

pneumoperitoneum in cases of perforation, Enteroliths, mottled calcification in the

mesenteric lymph nodes, and any evidence of ascitis may be suggested on the

plain film.

RADIOLOGICAL INVESTIGATIONS

• Evidence of tuberculosis in a chest radiograph supports the diagnosis, but a normal chest radiograph does not rule it out.

• The findings can be 1. miliary tuberculosis 2. atelectasis, emphysema, bronchiectasis, or parenchymal

opacity—any of these when present with pleural effusion or hilar lymphadenopathy indicates active disease; or

3. patchy consolidation or infiltration.• Signs of “old” tuberculosis (e.g., obliterated costophrenic

angle, calcified hilar lymph nodes, or a fibro-calcific lesion) are present in 20% of patients.

BARIUM STUDY

• Barium meal follow through examination as the best diagnostic test, demonstrating bowel lesions highly suggestive of tuberculosis such as multiple strictures and distended caecum or terminal ileum in 84% of cases.

Barium meal:

• mucosal irregularity and rapid emptying (ulcerative);

• flocculation and fragmentation of barium (malabsorption);

• stiffened and thickened folds;

• luminal stenosis with smooth but stiff contours (“hour glass stenosis”);

• dilated loops and strictures;

• displaced loops (enlarged lymph nodes); and

• adherent fixed and matted loops (adhesive peritoneal disease).

Barium enema:

• The following characteristics may be seen:• spasm and oedema of the ileocaecal valve (early

involvement);• characteristic thickening of the ileocaecal valve lips or

wide gaping of the valve with narrowed terminal ileum (“Fleischner” or “inverted umbrella sign”);

• “conical caecum”, a deformed and pulled-up caecum due to contraction and fibrosis;

• increased (obtuse) ileocaecal angle and dilated terminal ileum, appearing suspended from a retracted, fibrosed caecum (“goose neck deformity”) ;

• deformed and incompetent ileocaecal valve;

Barium enema:

• “purse string stenosis”—localised stenosis opposite the ileocaecal valve with a rounded-off smooth caecum and a dilated terminal ileum ;

• “Stierlin’s sign”—appears as a narrowing of the terminal ileum with rapid empyting into a shortened, rigid, or obliterated caecum; and

• “string sign”—a narrow stream of barium, indicating stenosis

• Both Stierlin and String signs can also be seen in Crohn’s disease.

• Enteroclysis followed by a barium enema may be the best protocol for evaluation of intestinal tuberculosis.

Barium enema:

• increased (obtuse) ileocaecal angle

• retracted, fibrosedcaecum (“goose neck deformity”) ;

ULTRASONOGRAPHY

• Ultrasonography being a widely available investigation, is now a ‘low threshold’ diagnostic procedure.

• It can accurately demonstrate small quantities of ascitic fluid and is an effective method for detection of peritoneal disease.

ULTRASONOGRAPHY

• Free or loculated ascitis.

• “Club sandwich” or “sliced bread” sign, due to localised fluid between radially oriented bowel loops.

• Multiple, thin, complete and incomplete septae are seen.

• Strands of septae may be due to high fibrin content of the exudative ascitic fluid.

ULTRASONOGRAPHY

• Floating echogenic debris.

ULTRASONOGRAPHY

• Lymphadenopathy is usually occurs in mesenteric, peri-pancreatic, periportal, and para-aortic groups of lymph nodes.

• Lymphadenopathy may be discrete or conglomerated (matted). The echotexture is mixed heterogenous(necrosis), in contrast to the homogenously hypoechoic nodes of lymphoma.

• Both caseation and calcification are highly suggestive of a tubercular aetiology.

ULTRASONOGRAPHY

• Multiple enlarged hypoechoic nodes

• Thickened hyperechoicmesentry.

ULTRASONOGRAPHY

• Bowel wall thickening—best appreciated in the ileocaecal region.

• A thickening of the small bowel mesentery of 15 mm or more and an increase in mesenteric echogenicity combined with mesenteric lymphadenopathy has been reported as the characteristic sonographic feature of early abdominal tuberculosis.

ULTRASONOGRAPHY

• Pseudo-kidney sign—involvement of the ileocaecal region that is pulled up to a subhepatic position.

• Peritoneal thickening and nodularity are the other sonographic features of abdominal tuberculosis.

• Ultrasound-guided fine-needle aspiration (FNA) biopsy has been used successfully in the diagnosis of abdominal tuberculosis

COMPUTED TOMOGRAPHY

• Till a few years ago, the only feature of abdominal tuberculosis reported on CT was the nonspecific appearance of high density ascites.

• The most common findings on CT that are highly suggestive of abdominal tuberculosis are

high density ascites, lymphadenopathy, bowel wall thickening, and irregular soft tissue densities in the omental

area

COMPUTED TOMOGRAPHY

• Abdominal lymphadenopathy is the commonest manifestation of tuberculosis on CT

• the lymph nodes involved most commonly include mesenteric, peri-portal, peri-pancreatic, and upper para-aortic groups of nodes.

CECT

• The CECT have been described as –

peripheral rim enhancement,

non-homogenous enhancement,

homogenous enhancement and

homogenous non-enhancement, in that order of frequency.

• Different patterns are seen same nodal group, possibly related to the different stages of the pathological process.

CECT

• Though not pathognomonic, the pattern of peripheral rim enhancement, could be highly suggestive of tuberculosis in an appropriate clinical setting.

CECT

• Conglomerate mass of 6cm.

• Enlarged nodes with hypo enhancing areas are seen.

CECT

• The presence of nodal calcification in the absence of a known primary tumour in patients from endemic areas suggests a tubercular aetiology .

• CECT imaging criteria differentiating abdominal lymph node enlargement due to tuberculosis or lymphoma suggested some differences in the anatomic distribution and the CT enhancement patterns

CECT

CECT FINDINGS Tuberculosis lymphoma

Lymph nodes lesser omental, mesenteric, and upper para-aortic

lower para-aortic lymph nodes

Lymphadenopathy features peripheral rim enhancement, frequently with a multilocularappearance

homogenous attenuation.

CECT

• Ascites can be free or loculated.• Characteristically, it is a high density ascites which could be

because of high protein and cellular contents of the fluid.• Mesenteric involvement and presence of macronodules (> 5mm in diameter), a thin omental line (fibrous wall covering the infiltrated

omentum), peritoneal or extraperitoneal masses with low density

centres and calcification, and splenomegaly or splenic calcification have been more

commonly seen with tuberculous peritonitis.

CECT

• High density ascitic fluid

• Peritonial and mesenteric thickening and enhancement are seen.

CECT

• The diagnosis of tuberculosis is suggestive when

loculated fluid collections are detected in the presence of omental infiltration,

peritoneal enhancement,

transperitoneal reaction, and

mesenteric or bowel involvement.

mural thickening affecting the ileocaecal region.

CECT

• Involvement of the liver and spleen in miliarytuberculosis may appear on CT as tiny low density foci widely scattered throughout the organ.

• The macronodular form of hepatosplenictuberculosis may be seen as multiple low attenuation (15-50 HU), 1-3 cm round lesions or simple tumour like masses.

CECT

• Multiple small hypoenhancing focci in liver parenchyma.

CECT

• Multiple hepatic and splenic abcessappearing as hypoenhancingnodules, well defined lesions.

CECT

• CT is more accurate than ultrasound in detecting abnormalities such as periportal and peripancreatic lymph nodes and bowel wall thickening.

• However, bowel wall dilatation can be better appreciated on ultrasound than on a CT scan.

• Magnetic resonance imaging (MRI), when compared to a CT scan, provides no additional information.

Imaging Bacterial Infection with Infecton

• A new radioimaging agent, Tc-99mciprofloxacin (Infecton) has been used to detect deep-seated bacterial infections, such as intraabdominal abscesses.

• Patients with suspected bacterial infection have been subjected to Infecton imaging and microbiological evaluation, reporting an overall sensitivity of 85.4% and a specificity of 81.7% for detecting infective foci.

Infecton

• Infecton may aid in the earlier detection and treatment of deep-seated infections, and serial imaging with Infecton might be useful in monitoring clinical response and optimisingthe duration of antimicrobial treatment.

ENDOSCOPY

• Endoscopic appearances in tuberculosis include hyperaemic nodular friable mucosa, irregular ulcers with sharply defined margins and undermined edges, and pseudopolyps.

• These may mimic inflammatory bowel disease and malignancy.

ENDOSCOPY

• Endoscopic biopsy may not reveal granulomas in all cases, as the lesions are submucosal.

• Biopsies from the edges and the base of the ulcer or multiple biopsies from the same site may increase the yield.

• Endoscopic biopsy specimens may be subjected to PCR for detection of AFB.

LAPAROSCOPY

• In peritoneal tuberculosis, laparoscopic appearances of thickened peritoneum along with whitish to yellowish miliary tubercles studded over the peritoneum and other viscera have been found to be more helpful in diagnosis of tuberculosis than either histological or bacteriological examination.

OTHER ARTICLES

• Diagnostic Laparoscopy Overtaking Other Diagnostic Modalities in Peritoneal Tuberculosis.

• Establishing the histological diagnosis can be difficult, frequently delaying treatment. In patients with the relevant background and clinical history, laparoscopy is the investigation of choice,and has the ability to take peritoneal biopsy ( histological confirmation) in a minimal invasive way. CT reliably demonstrates the entire range of findings which need interpretation in the light of clinical and laboratory data. Other diagnostic tests can supplement the diagnosis of peritoneal tuberculosis.

Results

• Diagnostic laproscopy was positive in 46 patients out of 50 biopsy proven cases of peritoneal tuberculosis with a sensitivity of 92% .

• CECT abdomen detected 30 out of 50 cases of abdominal tuberculosis with a sensitivity of 60%.

• Zeil Neilson staining for mycobacterium tubercle bacilli (MTB) of ascitic fluid was positive in 2 cases (4%).

• Culture for MTB was positive in 8 cases (16%). • Ascitic fluid analysis for ADA (> 33 U/L) showed a sensitivity

and specificity of 100% and 96% respectivily. • Mantoux test was positive in 23 cases (46%). Sensitivity of

ESR was 90%.

MANAGEMENT

• Management All patients with abdominal tuberculosis should be given standard full course of ATT.

• Conventional regimens suggest ATT for 12 to 18 months. However, the use of short course regimens for 6-9 months have been found to be equally effective.

MANAGEMENT

• Some authors have recommended the addition of corticosteroids in patients with peritoneal disease in order to reduce subsequent complications of adhesions. No controlled studies have been performed to show their benefit.

• Patients with intestinal obstruction due to strictures and hypertrophic lesions require surgical treatment.

MANAGEMENT

• Subacute intestinal obstruction or acute-on-chronic obstruction responds usually to conservative management and patients can be investigated later and managed electively.

• Despite being a treatable disease, abdominal tuberculosis carries a mortality of 4-12% which is largely due to associated problems of malnutrition, anaemia, and hypoalbuminaemiaand due to acute complications.

CONCLUSION

• Abdominal tuberculosis, a frequently recognized form extrapulmonary tuberculosis is increasing with increasing frequency of HIV infection. A high index clinical suspicion, appropriate and timely investigations, early diagnosis and treatment can considerably reduce the morbidity and mortality from this curable but potentially lethal disease.

Imaging bacterial infection with 99mTc-ciprofloxacin

(Infecton)K E Britton, D W Wareham, S S Das, K K Solanki, H

Amaral, A Bhatnagar,A H S Katamihardja, J Malamitsi, H M Moustafa, V E

Soroa, F X Sundram, A K PadhyJ Clin Pathol 2002;55:817–823

Aims:

• The diagnosis of deep seated bacterial infections, such as intra-abdominal abscesses, endocarditis, and osteomyelitis, can be difficult and delayed, thereby compromising effective treatment.

• This study assessed the efficacy of a new radioimaging agent, Tc-99m ciprofloxacin (Infecton), in accurately detecting sites of bacterial infection.

Patient selection:

• 879 patients, suspected to have bacterial infection from the different countries are included in this study to the types of infection imaged.

• Pregnant and lactating women or those with known hypersensitivity to quinolone antibiotics were excluded.

Preparation of Infecton

• Infecton was produced by reducing 2 mg of ciprofloxacin with 500 mg of stannous tartrate, at a buffered pH of 4.0, and radiolabelling with Technetium-99m up to 10 mCi (370 MBq).

• The agent was produced in house at St Bartholomew’s Hospital, London, and supplied as a two phase kit formulation, requiring 10 minutes to prepare.

Imaging protocol

• 10 mCi (370 MBq) of Tc-99m Infecton was injected intravenously over 40 seconds.

• 300 to 500 Kcounts were collected by the local single or double headed g camera, set with a low energy parallel hole general or high resolution collimator and peaked for 140 Kev with a 15% window.

• Anterior and posterior whole body static images were acquired at approximately one and four hours, and where indicated 24 hours after the injection.

Criteria for the interpretation of Infecton images

• A true positive result was one in which the image showed an area of abnormal uptake of the agent together with evidence of focal infection at the same site within five days of the image. A positive scan in a patient with probable infection was considered true positive.

• A false positive result was one in which the image findings were abnormal but there was no evidence of infection at the same site within five days of the image.

• A true negative result was one in which imaging was and there was no evidence of focal infection within five days of imaging. This included patients whose infection had resolved with antibiotic treatment at the time of imaging.

• A false negative result was one in which the image showed no abnormality but there was evidence of focal infection within five days of imaging. A negative scan in a patient with infection was considered false negative.

• A set of blood pool, 1, 3.5, and 24 hour images show focally increased and persistent uptake in the left index finger

DISCUSSION

• This multicentre study shows that Tc-99m labelled ciprofloxacin (Infecton) is able to diagnose and localise a wide range of bacterial infections accurately.

• The infections detected included osteomyelitis, septic arthritis, prosthetic device infections, endocarditis, deep seated abscesses, and extrapulmonary tuberculosis.

• In this study, the most successful results were seen in

osteomyelitis (sensitivity 90.5%, specificity 72.8%)

orthopaedic prosthesis (sensitivity 96%, specificity 91.6%),

with good sensitivity in microbiology positive tuberculosis (90%),

soft tissue (94.4%),

abdominal infections (93.3%),

excellent specificity in bacterial endocarditis (100%)

surgical wound infections (100%).

Take home messages

• Infecton gave an overall sensitivity of 85.4% and a specificity of 81.7% for detecting infective foci

• Sensitivity was higher (87.6%) in microbiologically confirmed infections

• Thus, Infecton is a sensitive technique, which could result in the earlier detection and treatment of a wide variety of deep seated bacterial infections

• The ability to localise infective foci accurately is also important for surgical intervention, such as the drainage of abscesses

• Serial imaging with Infecton might be useful in monitoring clinical responses and optimising the duration of antimicrobial treatment.

Thank you