Intestinal tuberculosis and tuberculous peritonitis

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Intestinal tuberculosis and tuberculous peritonitis GAO Hong Department of Gastroenterology, Zhongshan Hospital Fudan University

Objectives 1. To master the clinical manifestations, complications, diagnosis and differential diagnosis. 2. To master the diagnosis and differential diagnosis of ascites, especially SAAG and ADA; 3. To be familiar with the pathogenesis, classification, prevalence and the therapy of the diseases.

Pathogen Mycobacterium tuberculosis is the pathogen in most cases. Mycobacterium bovis in some parts of the world with no pasteurization of milk. Mycobacterium avium intracellulare has become a major pathogen in HIV patients. M. africanum, M. microti, and M. canetti

Epidemiology Second infectious disease in China The epidemic is being accelerated by coinfection with HIV and compounded by multidrug resistant TB; The incidence of GI TB is unknown; 20% pulmonary TB cases have extrapulmonary TB including GI TB; 15-20% GI TB case have pulmonary TB.

Following infection, the incubation period of TB range from a few weeks to a lifetime. Comstock et al. American Journal of Epidemiology 99:131-138

Intestinal Tuberculosis

Infective Route Ingestion of infected food or milk Swallowing of infected sputum from active lung disease Hematogenous spread from active pulmonary TB Direct spread from adjacent viscera

Site of disease TB can involve any region of GI tract; Ileum and cecum Ascending colon Jejunum Duodenum Stomach Esophagus Sigmoid colon rectum

Why is ileocecal region? Its richness of lymphoid tissue Relative stasis Increased absorption rate

Pathogenesis of TB: Infection - Immunity

FORMS OF GI TB Ulceroconstrictive 60% of patients Highly virulent Mostly small Intestinal Hypertrophic 10% of patients Chronic Mostly Ileocoecal Mixed 30% of patients (Howell & Knapton, 1964)

Three types of intestinal tuberculosis Ulcerative lesion(common) Hypertrophic lesion Ulcerohypertrophic lesions

T.B. transverse girdle ulcer small intestine

Sub mucosal muscular and subserous granulomas

Pathology Bowel wall-thicken Inflammatory mass Multiple transverse, circumferential ulcer, often with normal segments in between Mucosa-hyperemic, cobblestoned, edematous, ulcerated Serosal-tubercles;lymph nodes-enlarged

The approach to the subject was directed to these main points. Country and continent of origin. Age Gender Associated HIV infection Associated pulmonary disease Constitutional signs and symptoms Signs and symptoms related to the site of involvement in the G.I. tract

Manifestation Non-specific, usually insidious Abdominal pain(80-90%), distension, Diarrhea:mucoid,liquid to semisolid stools,rarely containing pus or blood abdominal mass Fever, weight loss, night sweat

Complication Intestinal hemorrhage Perforation Obstruction Fistula formation malabsorption

0% 5% 10% 15% 20% 25% 30% 35% pain 30.8% diarrhea 16.7% distention 9.2% mass 8.5% malabsorption 2.0% Local manifestations of ileocoecal cases (n= 520)

0% 5% 10% 15% 20% 25% 30% 35% 40% 45% pain 39.1% rectal bleeding 21.8% mass 12.1% distention 9.0% Local manifestations of colorectal cases (n= 463)

0% 10% 20% 30% 40% 50% 60% Dysphagia 57.0% Fistula 32.6% Haematemesis 12.8% Esophageal diverticula Epigastric pain Free mediastinal air Mediastinitis 2.3% 1.2% 1.2% 1.2% Local manifestations of esophagus cases (n= 86) Cairo University

0% 10% 20% 30% 40% 50% 60% Ulcer dyspepsia 52.4% Outlet obstruction 26.2% Mass 19.0% Haematemesis 11.9% Fistula 2.4% Local manifestations of gastroduodenal cases (n= 42)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% Perforation 81.3% Ascitis 20.5% Obstruction Abd.pain Ulcer Abd.mass Hge Fistula 11.6% 6.3% 4.5% 1.8% 0.9% 0.9% Local manifestations of small intestinal cases (n= 112)

Laboratory finding Blood routine test -mild anemia -normal white blood cell count -lymphopenia or lymphocytosis High erythrocyte sedimentation rate Tuberculin skin tests -PPD test, less helpful

Laboratory findings Identification of organism in tissues acid-fast stain culture of the excised tissue PCR assay T-spot test

Radiological examination Chest X-ray -abnormality(37-57%) -active pulmonary tuberculosis Plain X-ray films -diffuse abdominal calcifications Barium studies

X-ray A thicken bowel wall with distortion of the mucosal folds, ulceration,bowel stenosis, and pseudopolyps formation

Radiologic examination Stierlin Sign

Radiologic examination Fleischner's sign

Radiologic examination hypertrophic type

Radiologic examination ulcerohypertrophic type

CT Thickening of the ileocecal valve and medial wall of cecum Massive lymphadenopathy with central necrosis

Colonoscopy ascending colon(ulcerative lesion)

Hypertrophic lesion

Ileum and cecum:ulcerohypertrophic Ulcer Proliferation

Diagnoisis Histrory Clinical features X-ray PPD Anti-tuberculosis therapy Colonoscopy with biopsy

Differential diagnosis Crohn s disease

Carcinoma Amebiasis Schistosomiasis Syphilis and lymphogranuloma Gastrointestinal lymphoma

Treatment General: rest and nutrition Standard anti-tuberculosis treatment Ciprofloxacin, oxfloxacin, fluoroquinolone Corticosteroids

Surgery Assist diagnosis Treat complications -bowel obstruction -perforation -fistulae -hamorrhage -abscess perforation

Tuberculous peritonitis

Infective route Direct spread from (ruptured) lymph nodes and intraabdomininal organs Hematogenous seeding

pathology Multiple small, hard, raised, whitish tubercles studding the peritoneum A cecal tuberculoma, matterd lymph nodes, or omental involvement may form a palpable mass

Manifestation Systemic: Fever, night sweat, weight loss local: Abdominal pain Abdominal distension-ascites Diarrhea Nausea and vomiting Abdominal mass Doughy abdomen

0% 20% 40% 60% 80% 100% ascitis 90.6% pain 59.9% mass 23.7% lymphadenopathy jaundice 3.4% 3.4% distention 2.0% diarrhoea 1.0% Local manifestations of peritonitis cases (n= 881)

Laboratory finding Blood routine test ESR PPD test Test of ascites!!!

Paracentesis Exudative fluid High protein content Leukocytosis(lymphocytic) Adenosine deaminase(ada) increases

Gravity >1.016 SAAG<11g/L Protein: >30g/L White cell: >500 10 6 /L with lymphocyte 40-92%

Abdominal ultrasound Quick and inexpensive Detecting subclinical ascites and abdominal lymphadenopathy Assistant paracentesis

Radiology Chest X-ray CT -detecting lymphadenopathy -diffuse thickening of peritoneum -help differentiation

laparoscopy Correct diagnosis 72-95% Laparoscopic appearance at operation is more accurate than subsequent histology or microbiological culture Biopsy Contraindication-extensive adhesion

Laparoscopy Thickened. Hyperaemic, occasionally hemorrhagic, inflamed peritoneum Diffuse, white-yellowish uniform (3-5mm) tubercles deposits on peritoneum, omentum and organs Adhesions between organs and peritoneum

Typical tubercles Caseating granulomas epitheloid and with langerhans cells Chronic inflammation

T.B. peritonitis granulomata with fibrosis in the omentum Makram Milad Peritoneal T.B. Laparoscopy Hunter, Cairo University

Peritoneal T.B with adhesions Laparoscopy T.B. Peritoneal adhesions Ultrasonography Calcified T.B lymph nodes C.T. scan

Diagnosis History Clinical features Ascites X-ray PPD Diagnostic treatment Laparoscopy and biopsy

Differential diagnosis Ascites: malignant tumor cirrhosis Meigs syndrome Budd-Chiari syndrome constrictive pericarditis, etc. Abdominal mass: tumor, crohn s disease Abdominal pain Fever

treatment General treatment: rest and nutrition Standard anti-tuberculosis chemotherapy Abdominal paracentesis

Key Concepts for GI tuberculosis Sites: any region of the gastrointestinal tract. The most frequent sites are the ileum and cecum. Histological lesion: caseating granulomas. The common symptoms and signs: abdominal pain, weight loss, fever, diarrhea or constipation, and blood in the stool.

Key Concepts for GI tuberculosis The definitive diagnosis is made by identification of the organism in tissue, either by direct visualization with an acid-fast stain, by culture of the excised tissue, or by a polymerase chain reaction (PCR) assay. Standard anti-tuberculosis treatment gives a high cure rate.

Key points for tuberculous peritonitis Manifestions include low-grade fever, abdominal pain, anorexia, weight loss, and ascites. The peritoneal fluid characteristics: - protein concentration above 3 0g/L; - SAAG 11 g/l; - lymphocyte-predominant leukocytosis; - elevated ADA activity. Characteristic peritoneal nodules in laparoscopy in >90% of patients. Treatment is by standard anti-tuberculosis drugs.

CONCLUSION The disease is still and will remain a serious public health threat worldwide HIV infection is a main risk factor.

G.I. TUBERCULOSIS, A FINAL WORD Be aware of Abdominal Tuberculosis (Bouma et al., 1997)