1. بسم الله الرحمن الرحيم

2. Abdominal tuberculosis Prof of Hepatology-Alexandria UniversityBy
Amr Aly Abd El Moety
Prof of Hepatology-Alexandria University

3. Key points
Abdominal infection is more common with cavitating lung lesions than fibrotic lung lesions.
The ileocecum is the most commonly affected site.
Ulcerative, hyperplastic (resembling Crohn’s disease) and sclerotic forms are recognized in the intestine.
Peripheral lymphadenopathy (fixed or matted) is a helpful diagnostic clue.

4. Key points Only 30% have an abnormal chest X-ray.
Standard treatment consists of an induction phase for two months (rifampicin, isoniazid, pyrazinamide and ethambutol) followed by a continuation phase for four months (rifampicin and isoniazid).
MAC infection in immunocompromised patients frequently involves the gastrointestinal tract.

5. Introduction
Abdominal tuberculosis refers to disease of the gastrointestinal tract, lymph nodes, peritoneum, and intra- abdominal organs such as liver and spleen.

6. Epidemiology
Nearly a third of the world’s population (2 billion people) are infected with mycobacterium tuberculosis.
The WHO predicts continued increase in tuberculosis in underdeveloped countries.
By contrast in the West, after the resurgence of tuberculosis in the 1980s due to the AIDS epidemic, new infections have declined to the lowest level in 50 years.

7. Pathogenesis Swallowed sputum from pulmonary infection. Food.
The tubercle bacillus reaches the gastrointestinal tract by:
Swallowed sputum from pulmonary infection.
Food.
Adjacent tissues (pelvic organs).
lymphatic spread, and bloodstream.

8. In immunocompetent individuals, the infection is localized by the influx of specific lymphocytes and monocytes.
If the immune response is inadequate, the disease progresses locally and systemically by lymphohematogenous dissemination.

9. Classification of abdominal tuberculosis
Gastrointestinal
Ulcerative (ulcers: single, multiple, diffuse).
Hypertrophic (mass lesion).
Fibrotic (stricture formation).
Peritoneal
Ascites (localized, generalized).
Fibrotic or dry form (peritoneal adhesions, rolled up omentum).
Mixed form.

10. Classification of abdominal tuberculosis
Nodal
Mesenteric adenitis.
Mesenteric abscess.
Visceral disease
Liver, spleen, urinary tract, genital organs.

11. Intestinal tuberculosis
Pathology
Intestinal tuberculosis
The sites of involvement in order of decreasing frequency are: ileocecum, colon, jejunum, rectum and anal canal, duodenum, stomach, and esophagus.
Three pathological forms are described

12. Ulcerative variety
Mucosal ulcers cover a variable length of the bowel, with normal intervening mucosa. The ulcers are placed transversely and if the entire circumference is involved, the lumen becomes narrowed in a “napkin-ring”-like contraction. The ulcers are superficial and do not penetrate the muscularis mucosa.
The corresponding mesenteric surface has increased fat content and enlarged lymph nodes. Histology reveals granulation tissue, with neutrophils and microabscesses.

13. The characteristic morphological element is the tuberculous granuloma (caseating tubercule) : giant multinucleated cells (Langhans cells), surrounded by epithelioid cells aggregates, T cell lymphocytes and few fibroblasts. Granulomatous tubercules evolve to central caseous necrosis and tend to become confluent, replacing the lymphoid tissue.

14. Endoscopic lesions in a patient with intestinal tuberculosis.
(A) Ulcers over the ileocecal valve in a patient with intestinal tuberculosis (B) Multiple nodules and deep ulcers (with neoplasm-like appearance) in cecum with patulous ileocecal valve
(C) Fixed patulous ileocecal valve with nodules in cecum and ascending colon in a patient with intestinal tuberculosis. (D) Circumferential ulcerative lesion in a patient with tuberculosis.

15. Hyperplastic lesion
The bowel wall is thickened, measuring up to 3cm in width. The mucosal surface has a cobblestone pattern, with numerous pseudopolyps. The bowel assumes a tubular form with narrowing of the lumen. The hypertrophic variety typically affects the ileocecal region.
The intestinal lesion together with the increased mesenteric fat and enlarged lymph nodes may form and abdominal mass. Histology shows exuberant granulomatous tissue extending from the mucosa to the serosa, accompanied by hypertrophy of the muscularis layers.

16. Sclerotic form
Areas of marked narrowing of the bowel characterize the sclerotic form. There may be a single stricture or multiple strictures over a large segment of the intestine. The proximal bowel is dilated and enteroliths are noted at the stricture site.
Histology shows diffuse fibrosis extending from the submucosa to the serosa. Granulation tissue is limited to the bowel segment adjacent to the strictured areas.

17. Peritoneal tuberculosis
Ascites is the most frequent presentation of peritoneal disease. Typically, grayish white “military” nodules are scattered over the peritoneum. Fibrous bands or adhesions are common. The adhesions are mostly thin, but when thick and dense they divide the peritoneal cavity into compartments, with formation of loculated ascites
In some cases, the fibrotic reposes is so exuberant that the peritoneal cavity is completely obliterated, encasing the intestines like a cocoon. The omentum may become thickened, presenting as a transversely placed mass (“rolled up” omentum). Histology of the military nodules usually shows caseating necrosis and tuberculous granulomas.

19. Nodal tuberculosis
Isolated involvement of mesenteric nodes is uncommon. Enlarged lymph nodes may cause extrinsic compression and narrowing of the bowel lumen. Inflamed nodes can produce traction diverticula, seen mostly in the esophagus and colon.

20. Clinical presentation
The peak resentation is between 30 and 50 years of age. There is no gender difference in the West but women out-number men 2:1 in developing countries.
In patients with chronic liver disease there is 14 fold increase in frequency of tuberculosis more so in with patients with decompansated liver disease probably due to cirrhosis associated immune dysfunction syndrome and case fatality rate are high.

21. Systemic symptoms Fever ( low grade, with an evening spike).
Malaise, anorexia, and weight loss occur frequently.
Sweating can be profuse, often drenching clothes and bed sheets.
Pulmonary symptoms are present in patients with lung disease.
Menstrual abnormalities including amenorrhea are seen in 20% of women. Women may become sterile because of disease of the pelvic organs.

22. Abdominal symptoms
The characteristic symptom is abdominal pain the pain is localized to the site of the disease, usually the right iliac fossa but can be diffuse and nonspecific.
Typically, patients experience episodes of subacute intestinal obstruction with colicky pain, distention, and borborygmi, relieved to some extent by vomiting. The bowel habit is erratic, with episodes of diarrhea and constipation.

23. Patients may have symptoms related to disease at a specific site:
Dysphagia in esophageal involvement, ulcer-like pain, and gastric outlet obstruction in duodenal disease, and diarrhea with blood in diffuse colonic involvement.

24. Patients appear sick and emaciated. A low-grade temperature is noted.
Physical examination
Patients appear sick and emaciated.
A low-grade temperature is noted.
Peripheral lymphadenopathy should be carefully sought as it provides an easy source of diagnosis. Diseased nodes frequently fuse together (“matted”) and form adhesions with surrounding tissues; as a result, they appear “fixed” on examination and sinus tracks may form through the overlying skin.

25. Physical examination
A palpable mass in the right iliac fossa is typical, but masses may be felt at other sites including the epigastrium (rolled up omentum).
Visible peristalsis is noted in subacute bowel obstruction. Tenderness is localized to the site of disease.
Diffuse tenderness with a “doughy” feel is suggestive of peritoneal involvement.

26. Physical examination
Presence of an uneven abdominal distention indicates loculated ascites.
Fecal fistulae, and perianal fistulae and fissures may by noted.
Enlargement of liver and spleen indicated involvement of these organs.

27. Differential diagnosis
Lymphoma, carcinoma, and ameboma can mimic the abnormalities in tuberculosis. However, the condition most difficult to differentiate from tuberculosis is Crohn’s disease.
Diagnostic methods
Identification of M. tuberculosis provides a precise diagnosis. However, the organism is usually difficult to detect and a definitive diagnosis is possible only in a minority of individuals. Therefore, a therapeutic trial is justified in endemic countries.

28. Characteristic of intestinal tuberculosis and crohn's disease
Epidemiology
Developing
Developed countries
Clinical findings
Intestinal obstruction
50%
<10%
Diarrhea
30%
>80%
Fistulae
Anal lesions
<5%
Extraintestinal lesions
Pathology
Ulcers
Superficial, transverse
Deep, longitudinal
Granulomas
Confluent
Discrete
Caseation, AFB
Present
Never
Investigations
Positive tuberculin test
90%
Abnormal chest x-ray
Treatment
Steroid use
Worsening of disease
Beneficial response
Clinical course
Cured with treatment
Relapses despite treatment

29. Indirect tests
A high sedimentation rate is a common but nonspecific finding.
An abnormal chest X-ray is helpful (seen in 30% patients).
A positive tuberculin response is an excellent screening test in nonendemic countries, but is of little use in endemic areas because of high positive rates in healthy individuals.
Serological tests (based on specific anti-body response) are not used as they fail to differentiate active disease from past infection and from other mycobacterial infections.

30. Imaging studies
Plain X-rays show dilated bowel loops, air-fluid levels and calcified nodes.
Barium study, best performed by enteroclysis, is useful in establishing the location and extent of bowel involvement and identification of fistulae.
The classic radiological features are: contracted terminal ileum with a wide, open ileo-cecal valve (Fleischner sign) and a narrow ileum opening into a contracted cecum (Sterlin's sign) . However, overlapping small bowel loops may interfere with an accurate assessment, especially in the presence of bowel adhesions

31. Narrow ileum opening into a contracted cecum (Sterlin’s sign) Courtesy of Drs Nirmal Kumar and Veena Chaudhary, Maulana Azad Medical College, New Delhi, India.

32. Fleischner sign
Thinking of the ileocaecal valve lips and / or wide gaping of the valve, with narrowing of the terminal ileum .
Inverted umbrella sign .

33. Ultrasonography is very sensitive in detecting small quantities of fluid. Other abnormalities noted are: fibrous strands; enlarged nodes with hypoechoic centers (secondary to caseation necrosis) and alternatin pattern of echogenic and echo-free layers (club sandwich appearance) produced by diseased bowel loops with intervening fluid collection.

34. Computerized tomography provides better assessment of bowel wall thickness and mass lesions, enlarged nodes that have low-density centers with peripheral enhancement after contrast injection, diffuse or localized fluid collection and abnormality of pelvic organs.
CT scan showing enlarged retroperitoneal lymph nodes. Courtesy of Drs. Nirmal Kumar and Veena Chaudhary, Maulana Azad Medical College, New Delhi, India.

35. Endoscopy and biopsy
Diseased areas that are within reach should be examined with an endoscope. Biopsy specimens should be used for histopathology, acid- fast bacilli (AFB) staining and culture.
Aspiration cytology improves the yield in nodular lesions. Overall, a definitive diagnosis by endoscopy is made in one-third of patients. Another advantage of endoscopy is that conditions such as lymphoma and carcinoma can be excluded.

36. Tuberculous ascites
The ascitic fluid has high protein content (exudate), with a predominant lymphocytic response. A positive culture is obtained in <20% and AFB are detected infrequently (<5%).
Ascitic fluid adenosine deaminase, an enzyme released by stimulated T-cells, has a high sensitivity (94%) and specificity (92%).However the sensitivity drops to 30% in case of concomitant liver cirrhosis. Biopsy of nodules confirms the diagnosis in 90% of patients.

37. Treatment and prevention
Medical therapy consists of;
“Induction phase" of four drugs: isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin administered daily for 2 months .
“Contiuation phase” with two drugs: isoniazid and rifampin daily for 4 months.
Ourse duration of 6 month is acceblable insenitive infection.
Continuation phase over longer duration (9-12 months),using 3drugs in countries with a high prevalence of drug-resistant tuberculosis.

38. Adverse reactions
The most dreaded adverse reaction is hepatitis, seen more frequently (four times) with combined isoniazid and rifampin than isoniazid alone. Fulminant hepatitis can occur is susceptible individuals, often within 2 weeks of starting treatment.
When hepatitis occurs both drugs should be discontinued until transaminases become normal. Isoniazid is restarted in increasing doses under close monitoring of transaminase levels. Treatment should continue for months along with a second drug other than rifampin.

39. Complications and their management
The most common complication is acute intestinal obstruction.
Less frequent complications include
Perforation malabsorption, fistulae, and bleeding from a penetrating ulcer.
Emergent surgery; for complications such as free perforation, complete intestinal obstruction and acute bleeding.

40. Elective surgery; failure of medical therapy, usually for strictures
Elective surgery; failure of medical therapy, usually for strictures. Other indications are: bowel adhesions, abdominal abscess secondary to localized perforation, and fistulae.
The current surgical approach to intestinal strictures is stricturoplasty.
Peritoneal adhesions are treated by adhesiolysis and placement of reabsorbable cellulose membranes over the peritoneal surface.

41. Prognosis
Most patients respond well to treatment. Systemic symptoms subside within weeks, while the mucosal abnormalities take longer to disappear. Eventually, 70% patients have resolution of the radiologic abnormality.
Noncompliance and emergence of resistant bacteria are the primary reasons for treatment failure. Every effort should be made to obtain culture and drug sensitivity before initiating therapy. Patients with resistant bacteria should receive at least three drugs and treatment should be given for 12–24 months.

42. Medical treatment of tuberculosis
Drug
Daily dose
Adverse effect
Action
Isoniazid
5 mg/kg
Hepatitis
Stop if liver enzymes elevated (x3 ULN)
Peripheral neuropathy
Prophylactic vitamin B6
INH(100 &300 mg Tab) 
Interaction with phenytoin and cerbazepine
Rifampin
Remactazide( /75mg tab)
10 mg/kg
Same as for isoniazid
Thrombocytopenia
Monitor uric acid
Skin rash
Several drug interactions
Pyrazinamide
PTB( 500 mg tab)
15-30 mg/kg
Gout
Avoid in pregnancy
Ethambutol
Eitibi (200 mg tab)
15-25 mg/kg
Optic neuritis, color blindness
Baseline visual check; F/U as needed
Streptomycin
15 mg/kg
Ototoxicity
Baseline audiography; F/U as needed
Nephrotoxicity
Baseline renal tests; F/U as needed

43. New antituberculous treat.
Recently 2 drugs have been approved by FDA;
Bedaquiline (diarylquinoline) trade name
(Sirturo)It blocks ATPase of bacteria.
Dose:400 mg /day for 2 weeks followed by 200mg 3 times weekly
Delamanid(nitroimidazole)by otosuka company trade name Deltyaba
50 mg tab twice daily

44. Antituberculous in CLD and cirrhosis
No spesific guidelines
It is proposed to give;
Child Pugh less than 7 ( 2 drugs),
Child Pugh (single drug)
Child Pugh more than 11 (no drug)

45. Thank
you