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Gastrointestinal Tuberculosis


Gastrointestinal Tuberculosis

Article Author:
Raja Chandra Chakinala
Article Editor:
Akshay Khatri
Updated:
5/30/2020 8:35:30 PM
For CME on this topic:
Gastrointestinal Tuberculosis CME
PubMed Link:
Gastrointestinal Tuberculosis

Introduction

Gastrointestinal (GI) tuberculosis (TB) accounts for 1% to 3 % of all TB cases worldwide.[1][2] 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).[3][4] Diagnosis is challenging and is often delayed due to its non-specific presentation. GI TB responds well to standard antituberculous drugs. Surgery is only required in cases that develop complications such as strictures or obstruction, not responding to medical therapy. High clinical suspicion, early initiation of antituberculous therapy, and involvement of an interprofessional team are necessary for reducing morbidity and mortality.

Etiology

Infection of GIT by mycobacteria can occur in five ways:[5]

  1. Sputum ingestion by a patient with active pulmonary disease from Mycobacterium tuberculosis
  2. Hematogenous spread from a distant focus
  3. Lymphatic spread through infected nodes
  4. Direct extension from a contiguous site
  5. 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.[6]

The terminal ileum and ileocaecal valve are noted to be the most commonly involved segments.[6][7] 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 presence of M cells in the lymphatic tissue that can take up tubercle bacilli.[8]

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.[9] However, it can also affect proximal GIT.

Epidemiology

Extra-pulmonary TB accounts for about 12% of all tuberculosis cases, of which gastrointestinal tuberculosis accounts for 11% to 16% of the cases.[10] It thus makes up 1% to 3% of all TB cases.[1][2] 6% to 38% of patients with intra-abdominal TB may have concomitant pulmonary TB as well.[3][9] However, the diagnosis of concurrent active pulmonary disease depends on the criteria used in different studies.[7] Some studies reported that 31% to 50% of patients with AFB-smear positive cavitary TB have concomitant tuberculous enteritis.[11]

Some studies have reported a female preponderance of GI TB.[12] However, other studies have reported equal sex predisposition.[13] Interestingly, some studies in extrapulmonary TB showed that cultural and ethnic factors in different communities might lead to unequal environmental exposures.[14] This may account for differences in disease occurrence.

There is an unclear association of GI TB with the age of a patient. One study reported that middle-aged patients (reproductive age group) are most commonly affected. [15] While, in other studies, patients of a younger age group (age less than 25 years) had a higher incidence.[12] Some studies showed equal age distribution, which was attributed to a high prevalence of consanguinity, leading to overall reduced immune status across age groups.[14]

GI TB is commonly seen in populations with lower socioeconomic status. The concomitant contributors of illiteracy and malnutrition also play a role.[10] It is also seen with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS).[16] TB coinfections are the leading cause of death in patients with HIV/AIDs.[17]

In developed countries, TB is associated with patients with HIV/AIDS and in those who have immigrated from developing countries.[3][18] Interestingly, GI TB has been diagnosed in patients who had migrated many years prior.[18] However, in comparison to developing countries, there is an overall lower incidence and prevalence of GI TB.[19] 

In both developing and developed countries, GI TB has also been associated with patients being treated with anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents and those who have undergone solid-organ transplantation; after renal, renal-pancreas, liver, and cardiac transplants.[20][21][22][23][24] However, the overall reported incidence of GI TB after transplantation is still low. Of note, it is concerning that GI TB has also been reported in the immune-competent population.[18]

Pathophysiology

Esophageal TB

Esophageal involvement in TB occurs rarely.[25] 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.[26]

It may present with dysphagia and odynophagia.[25]

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 high acid environment, rapid transit time and a relative absence of lymphoid tissue.[27] However, they have been reported in the stomach and duodenum.[27][28]

It is reported to occur secondary to pulmonary TB.[29] Initially, its frequency was thought to be related to the severity of pulmonary involvement; however, independent cases have also been reported.[30]

Gastrointestinal (GI) tuberculosis in this anatomic location may lead to gastric outlet obstruction,[28] and surgical obstructive jaundice. [31]

TB of the Small and Large Intestine

Four major forms have been reported:[9][32]

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

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.[33][34] 

(E) Solid Organ TB:

Solid organs may be involved by hematogenous dissemination or direct intra-abdominal spread. [32] It usually occurs in immunocompromised patients (especially those with AIDS) and appears in a micronodular or macronodular fashion.[35] 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.[36]

Peritoneal Involvement

TB peritonitis exists in 5 main forms:[32]

  1. Ascitic
  2. Loculated (encysted)
  3. Plastic (fibrous)
  4. Purulent
  5. Nodular

Histopathology

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 [10][37]:

  1. Abdominal pain
  2. Anorexia
  3. Fever
  4. Change in bowel habits – diarrhea more common than constipation
  5. Nausea and vomiting
  6. Melena

However, some patients may not manifest any symptoms of GI TB.[38]

On examination, they are commonly found to have the following signs [10][37]:

  1. Weight loss
  2. Pallor and anemia
  3. Rectal bleeding
  4. Abdominal distension and ascites
  5. Hepatomegaly
  6. Splenomegaly
  7. Lymphadenopathy
  8. 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.

Evaluation

General Laboratory Testing

Patients with gastrointestinal tuberculosis are noted to have lower hemoglobin levels, lower serum albumin, and high C-reactive protein (CRP) levels.[39] 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).[40]

Mycobacterium-specific Testing

  1. Gastrointestinal tuberculosis is a paucibacillary disease. Acid-fast bacilli may not be isolated from clinical specimens.[41] Additionally, poor sensitivities are reported for acid-fast stain, cultures, and nucleic acid amplification tests.[42]
  2. Quantiferon testing (the standard interferon-gamma release assay test) may be false-negative in patients with extrapulmonary TB.[43]
  3. 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.[44] 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.[45]
  4. Adenosine deaminase (ADA) levels in the ascitic/peritoneal fluid have been reported to be a good diagnostic marker.[46]
  5. 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.[47] It may be useful in distinguishing intestinal TB from Crohn disease.[48] Multiplex PCRs that detect multiple TB genes have been found to have higher sensitivity and specificity and may also help differentiate from Crohn disease.[49][50]
  6. 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%.[51]
  7. There is a molecular probe that detects mutations in genes associated with rifampicin (rpoB gene) and isoniazid resistance (katG and inhA genes). In one study, it was found to have ≥99% sensitivity and specificity for detecting multidrug resistance (MDR) TB resistance, with faster results and positive results even in AFB smear-negative samples.[52]
  8. 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. Initial studies reported high sensitivity and specificity, with one meta-analysis showing no difference in performance with either fresh or frozen samples.[53][54] More recent studies and a recent meta-analysis showed that it has high specificity but limited sensitivity for detecting extra-pulmonary TB.[55] Thus, a positive result may rapidly identify TB cases, but a negative result does not rule it out. However, this may be a function of the volume of tissue available for testing. One retrospective study reported high sensitivity and specificity when performed on peritoneal tissue samples.[56]

Thus, to summarize, most of the mycobacterial-specific testing modalities for GI TB have high specificity but low sensitivity.

Imaging

1. Computed  tomography (CT) scan:

CT scan is the modality of choice in evaluating the extent and type of GI TB.[57] 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.[35]

Ascitic fluid has high protein and cellular content, creating areas of high attenuation on CT imaging. Other manifestations of peritoneal TB include plastic/fibrous type, which is seen as mesenteric and peritoneal thickening with loculated ascites. Another type is nodular/dry peritoneal TB, characterized by mesenteric nodular thickening and fibrous adhesions with a carcinomatosis appearance.[58]

CT enterography is a newer non-invasive technique for diagnosis and to assess the healing of TB lesions.[59]

2. Ultrasound

Ultrasound-guided aspiration may help in the diagnosis of solid-organ lesions.[60] 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.[61]

Gastroenterology Procedures

Colonoscopy may detect asymptomatic cases when performed for other reasons.[38] 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.[62]

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.[40][63]

The accuracy of therapeutic trials, as reported in different studies, has varied between 16% to 29%.[13][41] Response to therapy occurs rapidly, usually within two weeks.[4]

Treatment / Management

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.[64] 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).[63]

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.[65][66]

However, when there is a concern for disseminated disease, prolonged therapy may be needed.[18][37] 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.[63] One study reported the occurrence of multiple strictures occurring more frequently in patients who received prior ATT, compared to those who did not.[67] Additionally, an obstruction may worsen during ATT due to healing and scar formation.[68]

Drug-induced liver injury during ATT is the most common reason for discontinuation of therapy.[4] Concomitant Hepatitis B and C coinfection is reported to put patients at higher risk for liver injury.[69]

Endoscopic Intervention

Endoscopic balloon dilatation has been used for the management of ileal strictures and duodenal strictures.[70][71]

Surgical Therapy

Surgery may be needed in the setting of complications such as obstruction, perforation, and fistulation.[67]

Surgical options are categorized into three main broad groups [64][65][72]:

  1. 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. 
  2. 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. 
  3. 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.

Differential Diagnosis

“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.[73][74] TB lesions may show uptake of radioactive dye in positron emission tomography or computed tomography scan [75] and may also show elevated tumor markers.[76]

It has also been known to appear clinically similar to acute infections, such as appendicitis,[77] colitis,[78] acute cholecystitis,[79], and necrotizing fasciitis.[80]

Differentiation from Crohn Disease

Intestinal TB has very commonly been mistaken for Crohn disease.[81] The misdiagnosis rate can be as high as 50% to 70%.[82] Additionally, there have been reports of some patients with Crohn disease noted to have positive AFB staining.[83]

There have been several strategies aimed at distinguishing the two:

1.Clinical features:

One meta-analysis found that patients with TB were more commonly found to have a fever, night sweats, lung involvement, and ascites. Diarrhea, hematochezia, perianal disease, and the presence of extraintestinal manifestations were seen more in Crohn disease.[39][84]

2. Endoscopic features:

TB ulcers tend to be circumferential/transverse and surrounded by inflamed mucosa, with caseating granulomas. TB is also likely to produce a patulous ileocecal valve with heaped-up folds or a destroyed valve with a “fish-mouth” opening.[41][84]

Crohn disease is associated with longitudinal ulcers, aphthous ulcers, a cobblestone appearance, luminal stricture, mucosal bridge, skip lesions, and recto-sigmoid involvement.[84] Isolated involvement of the duodenum and jejunum is rare in intestinal TB and is more likely to be seen in Crohn disease.

3. Diagnostic tests:

Patients with GI TB have lower hemoglobin levels, lower serum albumin, and high C-reactive protein (CRP) levels; these may help differentiate it from Crohn disease.[39]

PCR testing for M. tuberculosis in tissue samples is highly specific for intestinal TB and may help in differentiating from Crohn disease.[48][50] One recent meta-analysis reported a pooled sensitivity and specificity of 44% and 95%, respectively, for the diagnosis of TB by PCR.[42]

Anti-Saccharomyces cerevisiae antibodies have been shown to be unreliable in the differentiation of the two diseases.[85]

4. Use of prediction models:

Several multi-parameter prediction models have been developed to differentiate the two diseases. However, these models have several distinct disadvantages, such as complex formulae, small sample size, heterogeneity of parameters, and lack of validation in different populations.[84][86]

5. Use of therapeutic trial:

Some researchers and groups have recommended a therapeutic trial of ATT to differentiate the two diseases.[87] When evaluated in a study, patients with intestinal TB who received ATT were found to have sustained clinical improvement and mucosal healing on repeat colonoscopy.[88] However, the proposed duration of the therapeutic trial, at which time ATT can be discontinued, is still to be formulated. 

Intestinal Sarcoidosis

Intestinal TB may also be mistaken for intestinal sarcoidosis, and differentiation between the two conditions may be difficult, even with biopsy.[89]

  • Crohn disease
  • Colorectal cancer
  • Esophageal cancer
  • Esophageal ulcers and tumors
  • Gastric cancer
  • Gastric ulcers
  • Sarcomas
  • Sarcoidosis

Prognosis

Untreated abdominal/gastrointestinal tuberculosis has a 6% to 20% mortality rate and may lead to complications that need surgical intervention.[90]

Complications

There are multiple complications reported due to gastrointestinal tuberculosis:[28][33][70][71][74][91][21][92][93][94]

  1. Upper and lower gastrointestinal bleeding
  2. Fistula occurring at different sites
  3. Obstruction of lumen of the gut 
  4. Stricture formation
  5. Intussusception
  6. Perforation
  7. Anemia
  8. Malnutrition, malabsorption, weight loss and deficiency of essential vitamins and minerals
  9. Chronic inflammatory demyelinating polyneuropathy was reported in one case

As noted earlier, intestinal TB has often been mistaken for Crohn disease. Treatment with immune-suppressive therapy in such cases, unfortunately, resulted in adverse outcomes.[81] Rarely, intestinal TB may develop as a complication during the treatment of Crohn disease with immunosuppressants. [95] Patients who develop active TB while receiving anti-TNF-alpha agents may show a paradoxical worsening of preexisting Crohn disease, or even the emergence of new lesions when these agents are withdrawn.[96]

Like other forms of TB, there is a concern for the emergence of MDR TB infections in the abdomen.[10] One study in Taiwan reported a prevalence of MDR TB in 13% of GI TB patients. However, a large proportion of them also had concomitant pulmonary TB.[97]

Deterrence and Patient Education

Gastrointestinal tuberculosis poses a diagnostic challenge as it typically presents with non-specific clinical and radiologic features. The diagnosis is often delayed due to its vague presentation resulting in various complications. A high index of clinical suspicion and appropriate use of various investigative modalities can aid in early diagnosis, thereby reducing associated morbidity and mortality. Antituberculous therapy is the mainstay of treatment, with surgery only required in a minority of cases.

Enhancing Healthcare Team Outcomes

Clinicians must keep gastrointestinal tuberculosis on the list of differential diagnoses when evaluating patients with new-onset Crohn disease or those with vague gastrointestinal symptoms and nonspecific test results. This is particularly important in those who have migrated from an endemic region and/or have other risk factors. Although it is more commonly seen in immunocompromised patients, it can also affect immunocompetent individuals.

Early consultation with experts in infectious diseases and gastroenterology, combined with an interprofessional approach and maintaining a high index of suspicion, is important in successful management.


References

[1] Sheer TA,Coyle WJ, Gastrointestinal tuberculosis. Current gastroenterology reports. 2003 Aug;     [PubMed PMID: 12864956]
[2] Farer LS,Lowell AM,Meador MP, Extrapulmonary tuberculosis in the United States. American journal of epidemiology. 1979 Feb;     [PubMed PMID: 425959]
[3] Horvath KD,Whelan RL, Intestinal tuberculosis: return of an old disease. The American journal of gastroenterology. 1998 May;     [PubMed PMID: 9625110]
[4] Rathi P,Gambhire P, Abdominal Tuberculosis. The Journal of the Association of Physicians of India. 2016 Feb;     [PubMed PMID: 27730779]
[5] de la Rua-Domenech R, Human Mycobacterium bovis infection in the United Kingdom: Incidence, risks, control measures and review of the zoonotic aspects of bovine tuberculosis. Tuberculosis (Edinburgh, Scotland). 2006 Mar;     [PubMed PMID: 16257579]
[6] Al-Bahrani ZR,Al-Saleem T, Intestinal tuberculosis in Iraq: a study of 50 cases. International surgery. 1982 Oct-Dec;     [PubMed PMID: 7183621]
[7] Palmer KR,Patil DH,Basran GS,Riordan JF,Silk DB, Abdominal tuberculosis in urban Britain--a common disease. Gut. 1985 Dec;     [PubMed PMID: 4085907]
[8] Kasulke RJ,Anderson WJ,Gupta SK,Gliedman ML, Primary tuberculous enterocolitis. Report of three cases and review of the literature. Archives of surgery (Chicago, Ill. : 1960). 1981 Jan;     [PubMed PMID: 6781447]
[9] Tabrisky J,Lindstrom RR,Peters R,Lachman RS, Tuberculous enteritis. Review of a protean disease. The American journal of gastroenterology. 1975 Jan;     [PubMed PMID: 1119469]
[10] Udgirkar S,Jain S,Pawar S,Chandnani S,Contractor Q,Rathi P, CLINICAL PROFILE, DRUG RESISTANCE PATTERN AND TREATMENT OUTCOMES OF ABDOMINAL TUBERCULOSIS PATIENTS IN WESTERN INDIA. Arquivos de gastroenterologia. 2019 Aug 13;     [PubMed PMID: 31460583]
[11] Tripathi PB,Amarapurkar AD, Morphological spectrum of gastrointestinal tuberculosis. Tropical gastroenterology : official journal of the Digestive Diseases Foundation. 2009 Jan-Mar;     [PubMed PMID: 19624086]
[12] Sreeramareddy CT,Panduru KV,Verma SC,Joshi HS,Bates MN, Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study. BMC infectious diseases. 2008 Jan 24;     [PubMed PMID: 18218115]
[13] Uygur-Bayramicli O,Dabak G,Dabak R, A clinical dilemma: abdominal tuberculosis. World journal of gastroenterology. 2003 May;     [PubMed PMID: 12717865]
[14] Al-Ghafli H,Varghese B,Enani M,Alrajhi A,Al Johani S,Albarrak A,Althawadi S,Elkizzi N,Al Hajoj S, Demographic risk factors for extra-pulmonary tuberculosis among adolescents and adults in Saudi Arabia. PloS one. 2019;     [PubMed PMID: 30917151]
[15] Chalya PL,Mchembe MD,Mshana SE,Rambau PF,Jaka H,Mabula JB, Clinicopathological profile and surgical treatment of abdominal tuberculosis: a single centre experience in northwestern Tanzania. BMC infectious diseases. 2013 Jun 8;     [PubMed PMID: 23758837]
[16] Rathi PM,Amarapurakar DN,Parikh SS,Joshi J,Koppikar GV,Amarapurkar AD,Kalro RH, Impact of human immunodeficiency virus infection on abdominal tuberculosis in western India. Journal of clinical gastroenterology. 1997 Jan;     [PubMed PMID: 9013351]
[17] Kantipong P,Murakami K,Moolphate S,Aung MN,Yamada N, Causes of mortality among tuberculosis and HIV co-infected patients in Chiang Rai, Northern Thailand. HIV/AIDS (Auckland, N.Z.). 2012;     [PubMed PMID: 23071410]
[18] Chien K,Seemangal J,Batt J,Vozoris NT, Abdominal tuberculosis: a descriptive case series of the experience in a Canadian tuberculosis clinic. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2018 Jun 1;     [PubMed PMID: 29862954]
[19] Lanjewar DN,Anand BS,Genta R,Maheshwari MB,Ansari MA,Hira SK,DuPont HL, Major differences in the spectrum of gastrointestinal infections associated with AIDS in India versus the west: an autopsy study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1996 Sep;     [PubMed PMID: 8879769]
[20] Shen Y,Ma HF,Yang YL,Guan JL, Ulcerative intestinal tuberculosis case as a complication of treatment by infliximab for intestinal Behçet's disease: A case report. Medicine. 2019 Oct;     [PubMed PMID: 31651888]
[21] Pattanashetti N,Gupta S,Rana S,Dahiya D,Das A,Kumar V,Rathi M,Kohli HS,Gupta KL,Ramachandran R, Intestinal Tuberculosis: A Rare Case of Massive Gastrointestinal Bleed in a Post-Renal Transplant Recipient. Indian journal of nephrology. 2019 Mar-Apr     [PubMed PMID: 30983756]
[22] Ulloa JG,Parekh J,Hope C,Roll GR, Case report of intestinal tuberculosis 6 years after simultaneous pancreas and kidney transplant. Transplantation proceedings. 2014 Sep;     [PubMed PMID: 24894420]
[23] Zhang XF,Lv Y,Xue WJ,Wang B,Liu C,Tian PX,Yu L,Chen XY,Liu XM, Mycobacterium tuberculosis infection in solid organ transplant recipients: experience from a single center in China. Transplantation proceedings. 2008 Jun;     [PubMed PMID: 18589112]
[24] Zedtwitz-Liebenstein K,Podesser B,Peck-Radosavljevic M,Graninger W, Intestinal tuberculosis presenting as fever of unknown origin in a heart transplant patient. Infection. 1999;     [PubMed PMID: 10885848]
[25] Dahale AS,Kumar A,Srivastava S,Varakanahalli S,Sachdeva S,Puri AS, Esophageal tuberculosis: Uncommon of common. JGH open : an open access journal of gastroenterology and hepatology. 2018 Apr;     [PubMed PMID: 30483561]
[26] Shad S,Rai AA,Soomro GB,Luck NH, Tuberculous Paraspinal Abscess Invading Esophagus: A Rare Cause of Dysphagia. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2018 Jul;     [PubMed PMID: 29950266]
[27] Balikian JP,Yenikomshian SM,Jidejian YD, Tuberculosis of the pyloro-duodenal area. Report of four cases. The American journal of roentgenology, radium therapy, and nuclear medicine. 1967 Oct;     [PubMed PMID: 6045399]
[28] Arabi NA,Musaad AM,Ahmed EE,Ibnouf MM,Abdelaziz MS, Primary gastric tuberculosis presenting as gastric outlet obstruction: a case report and review of the literature. Journal of medical case reports. 2015 Nov 18;     [PubMed PMID: 26577440]
[29] CHAZAN BI,AITCHISON JD, Gastric tuberculosis. British medical journal. 1960 Oct 29;     [PubMed PMID: 13692690]
[30] MITCHELL RS,BRISTOL LJ, Intestinal tuberculosis: an analysis of 346 cases diagnosed by routine intestinal radiography on 5,529 admissions for pulmonary tuberculosis, 1924-49. The American journal of the medical sciences. 1954 Mar;     [PubMed PMID: 13138589]
[31] Sharma BC,Prasad H,Bhasin DK,Singh K, Gastroduodenal tuberculosis presenting with massive hematemesis in a pregnant woman. Journal of clinical gastroenterology. 2000 Apr;     [PubMed PMID: 10777204]
[32] Engin G,Balk E, Imaging findings of intestinal tuberculosis. Journal of computer assisted tomography. 2005 Jan-Feb;     [PubMed PMID: 15665681]
[33] Shukla HS,Gupta SC,Singh G,Singh PA, Tubercular fistula in ano. The British journal of surgery. 1988 Jan;     [PubMed PMID: 3337948]
[34] Pandit K,Khanal S,Bhatta S,Trotter AB, Anorectal tuberculosis as a chronic rectal mass mimicking rectal prolapse in a child-a case report. Annals of medicine and surgery (2012). 2018 Dec;     [PubMed PMID: 30568795]
[35] Bächler P,Baladron MJ,Menias C,Beddings I,Loch R,Zalaquett E,Vargas M,Connolly S,Bhalla S,Huete Á, Multimodality Imaging of Liver Infections: Differential Diagnosis and Potential Pitfalls. Radiographics : a review publication of the Radiological Society of North America, Inc. 2016 Jul-Aug;     [PubMed PMID: 27232504]
[36] Rodriguez-Takeuchi SY,Renjifo ME,Medina FJ, Extrapulmonary Tuberculosis: Pathophysiology and Imaging Findings. Radiographics : a review publication of the Radiological Society of North America, Inc. 2019 Nov-Dec;     [PubMed PMID: 31697616]
[37] Muneef MA,Memish Z,Mahmoud SA,Sadoon SA,Bannatyne R,Khan Y, Tuberculosis in the belly: a review of forty-six cases involving the gastrointestinal tract and peritoneum. Scandinavian journal of gastroenterology. 2001 May;     [PubMed PMID: 11346208]
[38] Sato S,Yao K,Yao T,Schlemper RJ,Matsui T,Sakurai T,Iwashita A, Colonoscopy in the diagnosis of intestinal tuberculosis in asymptomatic patients. Gastrointestinal endoscopy. 2004 Mar;     [PubMed PMID: 14997132]
[39] Watermeyer G,Thomson S, Differentiating Crohn's disease from intestinal tuberculosis at presentation in patients with tissue granulomas. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 2018 Apr 25;     [PubMed PMID: 29843853]
[40] Sharma V,Mandavdhare HS,Lamoria S,Singh H,Kumar A, Serial C-reactive protein measurements in patients treated for suspected abdominal tuberculosis. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2018 Jun;     [PubMed PMID: 29301734]
[41] Singh V,Kumar P,Kamal J,Prakash V,Vaiphei K,Singh K, Clinicocolonoscopic profile of colonic tuberculosis. The American journal of gastroenterology. 1996 Mar;     [PubMed PMID: 8633510]
[42] Jin T,Fei B,Zhang Y,He X, The diagnostic value of polymerase chain reaction for {i}Mycobacterium tuberculosis{/i} to distinguish intestinal tuberculosis from crohn's disease: A meta-analysis. Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association. 2017 Jan-Feb;     [PubMed PMID: 28139494]
[43] Kim YJ,Kang JY,Kim SI,Chang MS,Kim YR,Park YJ, Predictors for false-negative QuantiFERON-TB Gold assay results in patients with extrapulmonary tuberculosis. BMC infectious diseases. 2018 Sep 10;     [PubMed PMID: 30200884]
[44] Li Y,Zhang LF,Liu XQ,Wang L,Wang X,Wang J,Qian JM, The role of in vitro interferonγ-release assay in differentiating intestinal tuberculosis from Crohn's disease in China. Journal of Crohn's     [PubMed PMID: 22405168]
[45] Bosco MJ,Hou H,Mao L,Wu X,Ramroop KD,Lu Y,Mao L,Zhou Y,Sun Z,Wang F, The performance of the TBAg/PHA ratio in the diagnosis of active TB disease in immunocompromised patients. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2017 Jun;     [PubMed PMID: 28392318]
[46] Riquelme A,Calvo M,Salech F,Valderrama S,Pattillo A,Arellano M,Arrese M,Soza A,Viviani P,Letelier LM, Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: a meta-analysis. Journal of clinical gastroenterology. 2006 Sep;     [PubMed PMID: 16940883]
[47] Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. American journal of respiratory and critical care medicine. 2000 Apr;     [PubMed PMID: 10764337]
[48] Amarapurkar DN,Patel ND,Amarapurkar AD,Agal S,Baigal R,Gupte P, Tissue polymerase chain reaction in diagnosis of intestinal tuberculosis and Crohn's disease. The Journal of the Association of Physicians of India. 2004 Nov;     [PubMed PMID: 15906835]
[49] Malik S,Sharma K,Vaiphei K,Dhaka N,Berry N,Gupta P,Sharma M,Mallick B,Kochhar R,Sinha SK, Multiplex Polymerase Chain Reaction for diagnosis of gastrointestinal tuberculosis. JGH open : an open access journal of gastroenterology and hepatology. 2019 Feb;     [PubMed PMID: 30834338]
[50] Jin XJ,Kim JM,Kim HK,Kim L,Choi SJ,Park IS,Han JY,Chu YC,Song JY,Kwon KS,Kim EJ, Histopathology and TB-PCR kit analysis in differentiating the diagnosis of intestinal tuberculosis and Crohn's disease. World journal of gastroenterology. 2010 May 28;     [PubMed PMID: 20503449]
[51] Mishra PK,Bhargava A,Punde RP,Pathak N,Desikan P,Jain A,Varshney S,Maudar KK, Diagnosis of gastrointestinal tuberculosis: Using cytomorphological, microbiological, immunological and molecular techniques - A study from Central India. Indian journal of clinical biochemistry : IJCB. 2010 Apr;     [PubMed PMID: 23105903]
[52] Barnard M,Albert H,Coetzee G,O'Brien R,Bosman ME, Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa. American journal of respiratory and critical care medicine. 2008 Apr 1;     [PubMed PMID: 18202343]
[53] Vadwai V,Boehme C,Nabeta P,Shetty A,Alland D,Rodrigues C, Xpert MTB/RIF: a new pillar in diagnosis of extrapulmonary tuberculosis? Journal of clinical microbiology. 2011 Jul;     [PubMed PMID: 21593262]
[54] Denkinger CM,Schumacher SG,Boehme CC,Dendukuri N,Pai M,Steingart KR, Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. The European respiratory journal. 2014 Aug;     [PubMed PMID: 24696113]
[55] Penz E,Boffa J,Roberts DJ,Fisher D,Cooper R,Ronksley PE,James MT, Diagnostic accuracy of the Xpert® MTB/RIF assay for extra-pulmonary tuberculosis: a meta-analysis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2015 Mar;     [PubMed PMID: 25686134]
[56] Dahale AS,Puri AS,Kumar A,Dalal A,Agarwal A,Sachdeva S, Tissue Xpert® MTB/RIF Assay in Peritoneal Tuberculosis: To be (Done) or Not to be (Done). Cureus. 2019 Jun 26;     [PubMed PMID: 31497439]
[57] Suri S,Gupta S,Suri R, Computed tomography in abdominal tuberculosis. The British journal of radiology. 1999 Jan;     [PubMed PMID: 10341698]
[58] Engin G,Acunaş B,Acunaş G,Tunaci M, Imaging of extrapulmonary tuberculosis. Radiographics : a review publication of the Radiological Society of North America, Inc. 2000 Mar-Apr;     [PubMed PMID: 10715344]
[59] Ma L,Zhu Q,Li Y,Li W,Wang X,Liu W,Li J,Jiang Y, The potential role of CT enterography and gastrointestinal ultrasound in the evaluation of anti-tubercular therapy response of intestinal tuberculosis: a retrospective study. BMC gastroenterology. 2019 Jun 26;     [PubMed PMID: 31242849]
[60] Suri R,Gupta S,Gupta SK,Singh K,Suri S, Ultrasound guided fine needle aspiration cytology in abdominal tuberculosis. The British journal of radiology. 1998 Jul;     [PubMed PMID: 9771382]
[61] Bhargava DK,Shriniwas,Chopra P,Nijhawan S,Dasarathy S,Kushwaha AK, Peritoneal tuberculosis: laparoscopic patterns and its diagnostic accuracy. The American journal of gastroenterology. 1992 Jan;     [PubMed PMID: 1530803]
[62] Mehta V,Desai D,Abraham P,Gupta T,Rodrigues C,Joshi A,Deshpande R,Sawant P,Ingle M,Rathi P,Mandot A, Do additional colonoscopic biopsies increase the yield of Mycobacterium tuberculosis culture in suspected ileo-colonic tuberculosis? Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology. 2018 May;     [PubMed PMID: 29967961]
[63] Sharma V,Mandavdhare HS,Dutta U, Letter: mucosal response in discriminating intestinal tuberculosis from Crohn's disease-when to look for it? Alimentary pharmacology     [PubMed PMID: 29446132]
[64] Sharma MP,Bhatia V, Abdominal tuberculosis. The Indian journal of medical research. 2004 Oct;     [PubMed PMID: 15520484]
[65] Mandavdhare HS,Singh H,Dutta U,Sharma V, A real-world experience with 6 months of antitubercular therapy in abdominal tuberculosis. JGH open : an open access journal of gastroenterology and hepatology. 2019 Jun;     [PubMed PMID: 31276036]
[66] Jullien S,Jain S,Ryan H,Ahuja V, Six-month therapy for abdominal tuberculosis. The Cochrane database of systematic reviews. 2016 Nov 1;     [PubMed PMID: 27801499]
[67] Alrashedi MG,Ali AS,Ali SS,Khan LM, Impact of thymoquinone on cyclosporine A pharmacokinetics and toxicity in rodents. The Journal of pharmacy and pharmacology. 2018 Oct;     [PubMed PMID: 30014468]
[68] Ha HK,Ko GY,Yu ES,Yoon K,Hong WS,Kim HR,Jung HY,Yang SK,Jee KN,Min YI,Auh YH, Intestinal tuberculosis with abdominal complications: radiologic and pathologic features. Abdominal imaging. 1999 Jan-Feb;     [PubMed PMID: 9933670]
[69] Lee SS,Lee CM,Kim TH,Kim JJ,Lee JM,Kim HJ,Ha CY,Kim HJ,Jung WT,Lee OJ,Kim DY, Frequency and risk factors of drug-induced liver injury during treatment of multidrug-resistant tuberculosis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2016 Jun;     [PubMed PMID: 27155184]
[70] Bhasin DK,Sharma BC,Dhavan S,Sethi A,Sinha SK,Singh K, Endoscopic balloon dilation of ileal stricture due to tuberculosis. Endoscopy. 1998 Mar;     [PubMed PMID: 9615897]
[71] Akarsu M,Akpinar H, Endoscopic balloon dilatation applied for the treatment of ileocecal valve stricture caused by tuberculosis. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2007 Jun;     [PubMed PMID: 17420160]
[72] Pujari BD, Modified surgical procedures in intestinal tuberculosis. The British journal of surgery. 1979 Mar;     [PubMed PMID: 427385]
[73] Kang MJ,Yi SY, Esophageal tuberculosis presenting as a submucosal tumor. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2008 Feb;     [PubMed PMID: 18237860]
[74] Cömert FB,Cömert M,Külah C,Taşcilar O,Numanoğlu G,Aydemir S, Colonic tuberculosis mimicking tumor perforation: a case report and review of the literature. Digestive diseases and sciences. 2006 Jun;     [PubMed PMID: 16865564]
[75] Razik A,Singh AN,Roy SG,Madhusudhan KS, Mesenteric Tuberculosis Masquerading as Carcinoid Tumor on Conventional Imaging and DOTANOC Positron Emission Tomography/Computed Tomography: Uncommon Presentation of a Common Disease. Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India. 2019 Jul-Sep;     [PubMed PMID: 31293302]
[76] Sun PJ,Lin Y,Cui XJ, Isolated pancreatic tuberculosis with elevated CA 19-9 levels masquerading as a malignancy: A rare case report and literature review. Medicine. 2018 Dec;     [PubMed PMID: 30593188]
[77] Kuntanapreeda K, Tuberculous appendicitis presenting with lower gastrointestinal hemorrhage--a case report and review of the literature. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2008 Jun;     [PubMed PMID: 18697397]
[78] Trad D,Norsaf B,Meriam S,Raja J,Ehsen BB, Acute severe colitis revealing tuberculosis. Gastrointestinal endoscopy. 2018 Oct;     [PubMed PMID: 29753037]
[79] Abu-Zidan FM,Zayat I, Gallbladder tuberculosis (case report and review of the literature). Hepato-gastroenterology. 1999 Sep-Oct;     [PubMed PMID: 10576349]
[80] Hefny AF,Abu-Zidan FM, Necrotizing fasciitis as an early manifestation of tuberculosis: report of two cases. Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma     [PubMed PMID: 20517775]
[81] Sato R,Nagai H,Matsui H,Yamane A,Kawashima M,Higa K,Nakamura S,Ohshima N,Tamura A,Hebisawa A, Ten Cases of Intestinal Tuberculosis Which Were Initially Misdiagnosed as Inflammatory Bowel Disease. Internal medicine (Tokyo, Japan). 2019 Jul 15;     [PubMed PMID: 30918188]
[82] Calciolari E,Donos N, The use of omics profiling to improve outcomes of bone regeneration and osseointegration. How far are we from personalized medicine in dentistry? Journal of proteomics. 2018 Sep 30;     [PubMed PMID: 29410240]
[83] Wang L,Hong Y,Wu J,Leung YK,Huang Y, Efficacy of thalidomide therapy in pediatric Crohn's disease with evidence of tuberculosis. World journal of gastroenterology. 2017 Nov 21;     [PubMed PMID: 29209113]
[84] Limsrivilai J,Shreiner AB,Pongpaibul A,Laohapand C,Boonanuwat R,Pausawasdi N,Pongprasobchai S,Manatsathit S,Higgins PD, Meta-Analytic Bayesian Model For Differentiating Intestinal Tuberculosis from Crohn's Disease. The American journal of gastroenterology. 2017 Mar;     [PubMed PMID: 28045023]
[85] Lackner AA,Smith MO,Munn RJ,Martfeld DJ,Gardner MB,Marx PA,Dandekar S, Localization of simian immunodeficiency virus in the central nervous system of rhesus monkeys. The American journal of pathology. 1991 Sep     [PubMed PMID: 1716047]
[86] Bae JH,Park SH,Ye BD,Kim SO,Cho YK,Youn EJ,Lee HS,Hwang SW,Yang DH,Kim KJ,Byeon JS,Myung SJ,Yang SK, Development and Validation of a Novel Prediction Model for Differential Diagnosis Between Crohn's Disease and Intestinal Tuberculosis. Inflammatory bowel diseases. 2017 Sep;     [PubMed PMID: 28682807]
[87] Epstein D,Watermeyer G,Kirsch R, Review article: the diagnosis and management of Crohn's disease in populations with high-risk rates for tuberculosis. Alimentary pharmacology     [PubMed PMID: 17539977]
[88] Pratap Mouli V,Munot K,Ananthakrishnan A,Kedia S,Addagalla S,Garg SK,Benjamin J,Singla V,Dhingra R,Tiwari V,Bopanna S,Hutfless S,Makharia G,Ahuja V, Endoscopic and clinical responses to anti-tubercular therapy can differentiate intestinal tuberculosis from Crohn's disease. Alimentary pharmacology     [PubMed PMID: 27813111]
[89] Sorrentino D,Avellini C,Zearo E, Colonic sarcoidosis, infliximab, and tuberculosis: a cautionary tale. Inflammatory bowel diseases. 2004 Jul;     [PubMed PMID: 15475755]
[90] Gavrila IL,Badea RI,Jude C,Socaciu MA,Comsa M,Badea AF, Ultrasound as the first imaging method in severe lung disease. Considerations about a case of pulmonary tuberculosis and review of the literature. Medical ultrasonography. 2020 Mar 1     [PubMed PMID: 32096796]
[91] Chong VH,Joseph TP,Telisinghe PU,Jalihal A, Chronic inflammatory demyelinating polyneuropathy associated with intestinal tuberculosis. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2007 Aug;     [PubMed PMID: 17712474]
[92] Goodrich-Blair H,Scarlato V,Gott JM,Xu MQ,Shub DA, A self-splicing group I intron in the DNA polymerase gene of Bacillus subtilis bacteriophage SPO1. Cell. 1990 Oct 19     [PubMed PMID: 2119891]
[93] Naicker S,Aboud O,Gharbi MB, Epidemiology of acute kidney injury in Africa. Seminars in nephrology. 2008 Jul     [PubMed PMID: 18620957]
[94] Ghoshal UC,Lakshmi CP,Kumar S,Das K,Misra A,Rai P,Mohindra S,Saraswat VA,Kumar A,Choudhuri G, Capsule endoscopy for obscure gastrointestinal bleeding in the tropics: report from India. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2011 Jan     [PubMed PMID: 21198912]
[95] Aleric I,Katalinic D,Vcev A,Brinar M, Pulmonary actinomycosis coexisting with intestinal tuberculosis as a complication of adalimumab treatment for Crohn's disease. Acta gastro-enterologica Belgica. 2017 Oct-Dec;     [PubMed PMID: 29560655]
[96] Arend SM,Leyten EM,Franken WP,Huisman EM,van Dissel JT, A patient with de novo tuberculosis during anti-tumor necrosis factor-alpha therapy illustrating diagnostic pitfalls and paradoxical response to treatment. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2007 Dec 1;     [PubMed PMID: 17990230]
[97] Lin PY,Wang JY,Hsueh PR,Lee LN,Hsiao CH,Yu CJ,Yang PC, Lower gastrointestinal tract tuberculosis: an important but neglected disease. International journal of colorectal disease. 2009 Oct;     [PubMed PMID: 19421759]