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Gastrointestinal Tuberculosis – Causes, Symptoms, Treatment

Gastrointestinal Tuberculosis is a chronic granulomatous disease caused by the aerobic bacteria Mycobacterium tuberculosis. The mycobacterium reaches the gastrointestinal tract via the hematogenous spread, ingestion of infected sputum, or direct spread from infected contiguous lymph nodes and fallopian tubes [rx–rx]. It can occur in the context of active pulmonary disease or as a primary infection without pulmonary involvement. The ileocecal region is the most commonly affected site; however, it can involve any part of the gastrointestinal tract (GIT). High clinical suspicion, early initiation of anti-tuberculous therapy, and involvement of an interprofessional team are necessary for reducing morbidity and mortality. This activity outlines the evaluation and management of gastrointestinal tuberculosis and highlights the role of the interprofessional team in managing patients with this condition.

Grossly abdominal tuberculosis presents in 3 morphological forms- ulcerative, hypertrophic and combination of both ulcers-hypertrophic [rx,rx,rx,rx]. A most common complication of intestinal tuberculosis is intestinal obstruction attributed to strictures or by adhesions approximately 3-20% of all cases of bowel obstruction are due to tuberculosis [rx,rx,rx].

Types of Gastrointestinal Tuberculosis

Tuberculosis of the ileum showing serosal tubercles

Tubercular lymphadenopathy – Abdominal lymphadenopathy is the most common manifestation of abdominal tuberculosis. The commonly involved lymph nodes are mesenteric nodes and omental nodes. They usually have central areas of caseous necrosis.^[rx]
Peritoneal tuberculosis – Peritoneal tuberculosis most often presents as abdominal pain and ascites. It can occur most commonly following the re-activation of a latent focus of tuberculosis.^[rx]
Intestinal tuberculosis – Tuberculosis of the intestine can affect multiple areas of the bowel simultaneously. The bacilli penetrate the mucosa, cause caseous necrosis and scarring.^[rx]
Hepatic tuberculosis – Hepatic tuberculosis can present as miliary hepatic tuberculosis and local hepatic tuberculosis. The proportion of hepatic involvement in disseminated tuberculosis is around 20 percent.^[rx]
- Other rare sites, such as genitourinary system, duodenum, esophagus, stomach, spleen. The commonest route of spread to these organs is hematogenous.^[rx]
Esophageal TB – Esophageal involvement in TB occurs rarely.[rx] It has been seen to occur due to spread from adjacent tissues. It usually involves the middle one-third of the esophagus, at the level of the carina.[rx] It may present with dysphagia and odynophagia.[rx]
Gastric and Gastroduodenal TB – Due to the protective fatty acid capsule of mycobacteria (as described earlier), proximal GIT lesions were thought to be rare. Additional factors that were thought to prevent TB in the stomach and duodenum were a high acid environment, rapid transit time, and a relative absence of lymphoid tissue.[rx] However, they have been reported in the stomach and duodenum.[rx][rx] It is reported to occur secondary to pulmonary TB.[rx] Initially, its frequency was thought to be related to the severity of pulmonary involvement; however, independent cases have also been reported.[rx]
Rectal and Anal TB – TB involving the rectal and anal areas may present as multiple fistulae (mimicking Crohn disease), a non-healing lesion after recent anal surgery, or a circumferential mass resembling rectal prolapse.[rx][rx]
Solid Organ TB – Solid organs may be involved by hematogenous dissemination or direct intra-abdominal spread. [rx] It usually occurs in immunocompromised patients (especially those with AIDS) and appears in a micronodular or macronodular fashion.[rx] The commonly involved organs are the gall bladder and liver.
Peritoneal TB – Peritoneal TB usually occurs with other forms of abdominal TB, with peritoneal involvement occurring after the rupture of necrotic lymph nodes. Lymph nodes in the small bowel mesentery and the retroperitoneum are commonly involved, and these may caseate and calcify. Ascites is the most frequent manifestation.[rx] Gastrointestinal (GI) tuberculosis in this anatomic location may lead to gastric outlet obstruction,[rx], and surgical obstructive jaundice. [rx]

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TB of the Small and Large Intestine

Four major forms have been reported:[rx][rx]

Ulcerative – the most common form. Usually presents with superficial transverse ulcers. It is more likely to be seen in the small intestine.
Hypertrophic – occurs as a hyperplastic reaction around the ulcer, producing an inflammatory mass. It is more likely to be seen in the cecum.
Ulcers-hypertrophic – a combination of ulcerative and hypertrophic forms may occur.
Fibrous stricturing – may lead to fibrosis and stricture formation, resulting in intestinal obstruction.

Peritoneal Involvement

TB peritonitis exists in 5 main forms:[rx]

Ascitic
Loculated (encysted)
Plastic (fibrous)
Purulent
Nodular

Causes of Gastrointestinal Tuberculosis

Infection of GIT by mycobacteria can occur in five ways:[rx]

Sputum ingestion by a patient with active pulmonary disease from Mycobacterium tuberculosis
Hematogenous spread from a distant focus
Lymphatic spread through infected nodes
Direct extension from a contiguous site
Ingestion of milk products infected with Mycobacterium Bovis – particularly seen with consumption of raw milk

Some authors have classified abdominal TB into two types: a primary form due to the direct ingestion of M. Bovis and a secondary form due to the spread of human bacillus from active pulmonary disease.[rx]

The terminal ileum and ileocaecal valve are noted to be the most commonly involved segments.[rx][rx] This occurs because of a combination of factors in this region. These include a narrow lumen, relatively increased physiological stasis (allowing for the absorption of the organism), minimal digestive activity, and the presence of M cells in the lymphatic tissue that can take up tubercle bacilli.[rx]

The mycobacteria have a fatty capsule that resists digestion, which interferes with their release early in the GIT. Thus, proximal GIT lesions were theoretically thought to be rare.[rx] However, it can also affect proximal GIT.

Diagnosis of Gastrointestinal Tuberculosis

Ischemia caused by vascular thrombosis may be responsible for tissue breakdown when there is the involvement of mesenteric vasculature by granulomatous inflammation was commonly associated with the ulcerative type with perforation. This suggests that ischemia secondary to vascular thrombosis is responsible for tissue breakdown. This implies that vasculitis plays an important role in the natural history of abdominal tuberculosis.

History and Physical

Patients with gastrointestinal tuberculosis commonly present with the following complaints [rx][rx]:

Abdominal pain
Anorexia
Fever
Change in bowel habits – diarrhea more common than constipation
Nausea and vomiting
Melena

However, some patients may not manifest any symptoms of GI TB.[rx]

On examination, they are commonly found to have the following signs [rx][rx]:

Weight loss
Pallor and anemia
Rectal bleeding
Abdominal distension and ascites
Hepatomegaly
Splenomegaly
Lymphadenopathy
Abdominal mass

A family history of TB may not be evident in all patients. Thus, GI TB must be considered even in the absence of family history. Similarly, only a few patients may have concomitant pulmonary TB or a past medical history of TB.

Lab Testing

General Laboratory Testing

Patients with gastrointestinal tuberculosis are noted to have lower hemoglobin levels, lower serum albumin, and high C-reactive protein (CRP) levels.[rx] CRP, erythrocytes sedimentation rate (ESR), and fecal calprotectin may also be useful in follow-up, as a surrogate marker for healing while on antituberculosis treatment (ATT).[rx]

Mycobacterium-specific Testing

Gastrointestinal tuberculosis – is a paucibacillary disease. Acid-fast bacilli may not be isolated from clinical specimens.[rx] Additionally, poor sensitivities are reported for acid-fast stain, cultures, and nucleic acid amplification tests.[rx]
Quantiferon testing – (the standard interferon-gamma release assay test) may be false-negative in patients with extrapulmonary TB.[rx] The commercially available interferon-gamma release assay is reported to have better sensitivity and specificity than the traditional tuberculin skin test in the diagnosis of GI TB.[rx] However, it cannot discriminate between active and latent infections. A further calculation of the ratio of TB-specific antigen (TBAg) to phytohaemagglutinin (PHA), known as the TBAg/PHA ratio, could increase the specificity for distinguishing active TB from latent infection.[rx]
Adenosine deaminase (ADA) – levels in the ascitic/peritoneal fluid have been reported to be a good diagnostic marker.[rx]
Polymerase chain reaction (PCR) testing – for M. tuberculosis on clinical specimens can be used as an adjunct for initial diagnosis, but should not be used for follow-up. This is because it cannot differentiate between living and dead M. tuberculosis. Thus, it can remain positive even after the completion of anti-TB treatment and the death of the bacteria.[rx] It may be useful in distinguishing intestinal TB from Crohn’s disease.[rx] Multiplex PCRs that detect multiple TB genes have been found to have higher sensitivity and specificity and may also help differentiate from Crohn’s disease.[rx][rx]
Fluorescence resonance energy transfer hybridization – Another new molecular technique involves a real-time assay using fluorescence resonance energy transfer hybridization probes. In patients with clinical and radiological suspicion of TB, but negative AFB smear and culture, it was reported to have a positivity index of 36%.[rx][rx]

The World Health Organization (WHO) currently recommends a test that amplifies the genomic DNA by PCR assay for diagnosis of TB, with results provided within 2 hours. It combines a nested PCR technique with automated amplification and detects M. tuberculosis and rifampicin resistance gene. The rifampicin resistance gene functions as an accurate surrogate marker for MDR TB.

Imaging

Computed tomography (CT) scan – CT scan is the modality of choice in evaluating the extent and type of GI TB.[rx] It appears as asymmetric wall thickening of the terminal ileum, cecum, or ileocecal valves associated with necrotic lymph nodes. After chronic inflammation, the cecum may appear small and irregular due to fibrosis and stenosis. Solid-organ involvement manifests as multiple small hypoattenuating nodules seen on the surface and throughout the parenchyma.[rx] CT enterography is a newer non-invasive technique for diagnosis and to assess the healing of TB lesions.[rx]
Ultrasound – Ultrasound-guided aspiration may help in the diagnosis of solid-organ lesions.[rx] Ultrasound-guided aspiration with the assistance of laparoscopy (as needed) helps in the diagnosis of the ascitic type of peritoneal TB and tuberculous lymph node involvement.[rx]
Gastroenterology Procedures – Colonoscopy may detect asymptomatic cases when performed for other reasons.[rx] Biopsies obtained by colonoscopy have been reported to have as high as 80% diagnostic accuracy. The yield from culture has been reported to be higher when multiple tissue biopsies are obtained during colonoscopy.[rx]
Therapeutic Trials – In some cases, when diagnostic testing is unyielding, but the clinical suspicion is high, patients are started empirically on antituberculosis therapy (ATT). Response to therapy is proposed as a criterion for the diagnosis of GI TB.[rx][rx] The accuracy of therapeutic trials, as reported in different studies, has varied between 16% to 29%.[rx][rx] Response to therapy occurs rapidly, usually within two weeks.[rx]

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Treatment of Gastrointestinal Tuberculosis

Medical Therapy

A standard four-drug regimen, consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol, is recommended for ATT in intra-abdominal/gastrointestinal tuberculosis. These four drugs are used thrice weekly for the initial two months, followed by isoniazid and rifampin for an additional four months.[rx] ATT is usually reported to be highly effective with good cure rates. Healing of intestinal ulcers can be seen as early as the end of the ATT initiation phase (2 months).[rx]

Most treatment guidelines recommend a 6-month course of ATT for luminal TB. Prospective, randomized controlled studies and as well as a Cochrane systematic review have confirmed good cure rates with six months of therapy, instead of 9 months, with the added benefits of reduced cost and increased compliance.[rx][rx]

However, when there is a concern for disseminated disease, prolonged therapy may be needed.[rx][rx] Thus, each patient should be evaluated on an individual basis. Consultation with an expert in infectious diseases is recommended.

Response to ATT occurs by mucosal healing. However, strictures, polyps, and hypertrophic lesions may persist despite the use of ATT.[rx] One study reported the occurrence of multiple strictures occurring more frequently in patients who received prior ATT, compared to those who did not.[rx] Additionally, an obstruction may worsen during ATT due to healing and scar formation.[rx]

Drug-induced liver injury during ATT is the most common reason for discontinuation of therapy.[rx] Concomitant Hepatitis B and C coinfection is reported to put patients at higher risk for liver injury.[rx]

Endoscopic Intervention

Endoscopic balloon dilatation has been used for the management of ileal strictures and duodenal strictures.[rx][rx]

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Surgical Therapy

Surgery may be needed in the setting of complications such as obstruction, perforation, and fistulation.[rx]

Surgical options are categorized into three main broad groups [rx][rx][rx]:

Bypassing of involved bowel segments – entero-enterostomy, ileo-transverse colostomy. These procedures are not routinely done as they are usually complicated by blind loop syndrome, fistula formation, and recurrent disease in the remaining segments.
Radical resection of involved segments – hemicolectomy. Tuberculous bowel perforations are usually treated with resection of involved segments and primary anastomosis. This can be combined with effective ATT to eradicate the disease. However, these surgeries are hindered by the malnourished status of most patients, making them poor surgical candidates.
Conservative surgeries, such as like strictureplasty, in strictures causing more than 50% luminal compromise. Surgery may be needed in patients with persistent strictures while on ATT, as well as those with multiple strictures that are less likely to respond to ATT.

“The great mimicker”

Gastrointestinal tuberculosis is known as the great mimicker. It has been reported to mimic esophageal cancer, esophageal ulcers and tumors, gastric ulcers, gastric cancer, colorectal cancer, and sarcomas.[rx][rx] TB lesions may show uptake of radioactive dye in positron emission tomography or computed tomography scan [rx] and may also show elevated tumor markers.[rx]

Complications

There are multiple complications reported due to gastrointestinal tuberculosis:[rx]

Upper and lower gastrointestinal bleeding
Fistula occurring at different sites
Obstruction of lumen of the gut
Stricture formation
Intussusception
Perforation
Anemia
Malnutrition, malabsorption, weight loss, and deficiency of essential vitamins and minerals
Chronic inflammatory demyelinating polyneuropathy was reported in one case

As noted earlier, intestinal TB has often been mistaken for Crohn’s disease. Treatment with immune-suppressive therapy in such cases, unfortunately, resulted in adverse outcomes.[rx] Rarely, intestinal TB may develop as a complication during the treatment of Crohn disease with immunosuppressants. [rx] Patients who develop active TB while receiving anti-TNF-alpha agents may show a paradoxical worsening of preexisting Crohn’s disease, or even the emergence of new lesions when these agents are withdrawn.[rx]

References