- Email: [email protected]
Abdominal Tuberculosis in Southeastern Taiwan: 20 Years of Experience
ORIGINAL ARTICLE
Abdominal Tuberculosis in Southeastern Taiwan: 20 Years of Experience Huan-Lin Chen,1 Ming-Shiang Wu,2 Wen-Hsiung Chang,3,4 Shou-Chuan Shih,3,4 Hsin Chi,4,5 Ming-Jong Bair1* Background/Purpose: Abdominal tuberculosis (TB) is a rare manifestation of extrapulmonary TB. This disease entity can be overlooked, and its early diagnosis is difficult because of its variable manifestations and lack of specific symptoms. Methods: The clinical and diagnostic features, treatment, and outcome of patients with abdominal TB at a major hospital in southeastern Taiwan from January 1987 to December 2006 were investigated. Results: Twenty-one patients with abdominal TB identified during the 20-year period were included. A predominance of male (13/21, 61.9%) and Taiwanese aborigine (15/21, 71.4%) patients was noted. Middleaged (30–50 years) patients with alcoholic liver cirrhosis had the highest risk. Common presenting features included abdominal pain (18/21, 85.7%), fever (16/21, 76.2%), ascites (13/21, 61.9%), and weight loss (12/21, 57.3%). The mean time to reach a diagnosis was 48 ± 10 days. Tuberculous peritonitis was noted in 11 patients, with a high correlation with liver cirrhosis (p = 0.0237, Fisher’s exact test). The other patients were diagnosed with TB of the gastrointestinal tract (n = 6), urinary tract (n = 2), and pelvis (n = 2). Abdominal sonography and abdominal computed tomography were helpful for diagnosis, by revealing ascites and thickening of the peritoneum. Pulmonary involvement was noted in 11 patients. Most of the patients (16/21, 76.2%) improved with anti-tuberculosis therapy, and five patients died from sepsis and respiratory failure. Conclusion: Abdominal TB is a rare manifestation of extrapulmonary TB, even in southeastern Taiwan where TB is prevalent. Delay in diagnosis is common and abdominal TB should be included in the differential diagnosis of middle-aged aborigine men with alcoholic liver cirrhosis and peritonitis. [J Formos Med Assoc 2009;108(3):195–201] Key Words: abdominal tuberculosis, extrapulmonary tuberculosis, gastrointestinal tuberculosis, tuberculosis, tuberculous peritonitis
cases are pulmonary TB.3 However, extrapulmonary organ involvement in TB is not uncommon. For human immunodeficiency virus (HIV)-negative patients, the frequency has been reported as 10–15%, in contrast to > 50% in HIV-positive patients.1–3 Abdominal TB is a rare manifestation
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It has been present in humans since antiquity and has become a major cause of death and disability in most parts of the world, especially in developing countries.1,2 The disease can affect multiple body systems, and most
©2009 Elsevier & Formosan Medical Association .
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1
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, 2Division of Gastroenterology, Department of Internal Medicine, Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, 3Division of Gastroenterology, Department of Internal Medicine, and 5Department of Infectious Disease, Mackay Memorial Hospital, and 4Mackay Medicine, Nursing and Management College, Taipei, Taiwan. Received: June 18, 2008 Revised: September 9, 2008 Accepted: September 17, 2008
J Formos Med Assoc | 2009 • Vol 108 • No 3
*Correspondence to: Dr Ming-Jong Bair, Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, No. 1, Lane 303, Changsha Street, Taitung, Taiwan. E-mail: [email protected]
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of extrapulmonary TB, and a prevalence of around 3% has been noted previously.3 It may involve the gastrointestinal tract, peritoneum, mesenteric lymph nodes, genitourinary tract in the abdomen, or other solid organs (e.g. liver, spleen and adrenal glands).1,3,4 According to the Global Competitiveness Report 2006–2007,5 Taiwan ranks 60th on a worldwide scale in terms of the effectiveness of TB control. This means that TB control in Taiwan is still lagging behind that in other developed countries. A study of extrapulmonary TB in Taiwan, from 1996 to 2003 found that 23–27% of TB cases are extrapulmonary,6 which is similar to the rate found in Hong Kong in 1996.7 Two previous studies from Taipei Veterans General Hospital have demonstrated abdominal TB in 1991 and 1995.8,9 Surprisingly, a very high proportion of patients (74.1–79%) received laparotomy for diagnosis of abdominal TB at that time. These reports highlight the fact that abdominal TB is frequently misdiagnosed. Compared with western Taiwan, eastern Taiwan has a higher incidence and mortality rate of TB.10,11 In 2005, Taitung County, a southeastern province of Taiwan, had the highest mortality rate, with as many as 12.52 deaths per 100,000.10 It appears from these figures that Taitung is an epidemic area for TB in Taiwan. We conducted a retrospective study to collect information on the diagnostic features, clinical presentation, mycobacteriology, treatment, and outcome of abdominal TB over a 20-year period at Mackay Memorial Hospital, Taitung Branch, a major hospital in southeastern Taiwan.
Methods Patient information was obtained from the Mackay Memorial Hospital, Taitung Branch. We retrieved the records of all patients diagnosed with abdominal TB between January 1987 and December 2006. Patients were confirmed to have intra-abdominal TB (i.e. gastrointestinal tract, peritoneum, mesenteric lymph nodes, genitourinary 196
tract in the abdomen, or other solid organs, such as liver, pancreas or spleen). Patients who also had pulmonary involvement were considered for inclusion. Diagnosis of abdominal TB was based upon: (1) a positive acid-fast bacilli smear or culture; (2) histopathology showing tubercular granuloma (with or without caseation); (3) radiologic features compatible with tuberculosis on barium X-rays, ultrasound, or computed tomography (CT) of the abdomen; and (4) patients with a high index of clinical suspicion, with negative diagnostic workup, but who still showed a good response to a therapeutic trial with anti-TB agents.1 We collected details of demographics, clinical features associated with medical illness, and family and past history of TB. We recorded data on laboratory tests, chest and abdominal imaging, histopathology, acid-fast bacilli staining and culture, ascitic fluid analysis, upper gastrointestinal endoscopy, colonoscopy, laparoscopy and laparotomy. We also reviewed the clinical course of the disease and its complications. Additional epidemiologic and clinical information was obtained from detailed interviews conducted by telephone, using a standardized questionnaire. SPSS version 12.0 (SPSS Inc., Chicago, IL, USA) was used for data analysis. Descriptive analysis was performed for demographic, clinical and radiographic features.
Results Patient characteristics A total of 21 patients with abdominal TB were identified and included during the 20-year study period. Thirteen of these patients were male, and 15 were Taiwanese aborigines. Patient age ranged from 22 to 88 years, with a mean age of 50 ± 18 years. The most common age group was 30–50 years (Figure 1). Only two patients had a past medical history of pulmonary TB. History of other underlying diseases, such as liver cirrhosis (n = 7), renal failure (n = 4), diabetes (n = 1), and hypertension (n = 1), was recorded. There were also 12 patients who consumed excess alcohol and four J Formos Med Assoc | 2009 • Vol 108 • No 3
Abdominal tuberculosis in Southeastern Taiwan
7
Male Female
6 1
Number
5 4
5
2
1
1 0
2
3
3
0 0–10
0 11–20
1 21–30
2 31–40
41–50 51–60 Age (yr)
1
3
0 1
61–70
0 71–80
1 > 80
Figure 1. Age and gender distribution of patients with abdominal tuberculosis.
Table 1. Clinical symptoms of patients with abdominal tuberculosis (n = 21) Symptoms Abdominal pain Fever Ascites Weight loss Abdominal distension Fatigue Anorexia Diarrhea Ill-looking
n 18 16 13 12 10 8 8 4 2
patients who had a family history of TB. Abdominal pain was the most common symptom (n = 18) (Table 1). In addition, abdominal TB was found incidentally in three patients with: left ovary fibroma and TB peritonitis; pulmonary and bladder TB; and sigmoid diverticulitis with perforation and small bowel TB.
Diagnostic methods The average time to diagnosis was 48 ± 10 days. Abdominal ultrasound (n = 11) and CT (n = 10) were commonly used for diagnosis, which showed ascites and thickening of the peritoneum. Other abdominal investigations, such as gastroduodenoscopy (n = 4), colonoscopy (n = 1), barium examination (n = 2), and laparoscopy (n = 2) were less common. Ascites was present in 13 patients, but TB culture of ascites was positive in only five patients. Other positive TB culture included that of sputum, lower leg wound, mesenteric biopsy, J Formos Med Assoc | 2009 • Vol 108 • No 3
peritoneal specimen, and urine. Caseating granulomatous inflammation was found in 11 patients undergoing mass resection or endoscopic/ laparoscopic biopsy. Only one patient met the criterion of a good response to a therapeutic trial of anti-TB agents. Pulmonary TB was also found in 11 patients, including one with miliary TB and one with pleural effusion, and six of them were diagnosed with concurrent TB peritonitis. In addition, most of the patients had hypoalbuminemia (2.2 ± 0.8 g/dL; normal range, 3.5–5.0 g/dL) and anemia (9.9 ± 2.5 g/dL; normal range, 11–18 g/dL).
Location TB peritonitis was the most common diagnosis (n = 11, Figure 2). Six cases involved the gastrointestinal tract (3 cecum and terminal ileum, 2 small bowel, 1 esophagus and stomach). The patient with disseminated TB had esophageal, gastric, pulmonary, and lower leg wound involvement. He had alcoholic liver cirrhosis and diabetes and survived after anti-TB and antibiotic treatment. In addition, one of the patients also had peritoneal involvement, and another had orchiectomy because of testicular invasion. Two patients with pelvic mass and ovarian TB were diagnosed from surgical specimens, and one also had peritoneal involvement. Only two cases involved the urinary tract. One was diagnosed with TB from bladder pathology, and the other was confirmed by urine culture. Concurrent pulmonary TB was noted in 11 patients. 197
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Location GU tract, 2
Pelvis, 1
Pelvis + peritonium, 1
GI tract, 4
GI tract + peritonium, 2
Peritonium, 11
Figure 2. Predominant sites of involvement in abdominal tuberculosis (n = 21).
Table 2. Comparison of mortality factors
Onset year Sex Age (yr) Aborigine Symptoms Smoking Drinking Underlying disease Diagnostic method Ascites Pulmonary TB TB peritonitis Hemoglobin (g/dL) Albumin (g/dL)
Case 1
Case 2
Case 3
Case 4
Case 5
1990 F 32 Yes ABD pain Yes Yes Cirrhosis Echo No Yes Yes 15 1.4
1995 M 61 Yes Fatigue Yes Yes Cirrhosis CT AFB (+) Yes Yes 8.3 1.6
2000 M 58 No ABD pain Yes Yes Uremia Ascites from CAPD AFB (+) Yes Yes 8 2.3
2004 M 44 Yes ABD distension Yes No Cirrhosis Echo AFB (+) Yes Yes 9.6 2.9
2006 F 62 No ABD pain No Yes Diabetes Echo AFB (+) Yes Yes 9.8 1.1
ABD = abdominal; Echo = abdominal echo; CT = computed tomography; CAPD = continuous ambulatory peritoneal dialysis; AFB = acid-fast bacilli.
Treatment and outcome The clinical condition improved after anti-TB agents in 16 patients. Anti-TB treatment consisted of isoniazid, rifampicin, ethambutol, streptomycin and pyrazinamide in various combinations for 9–12 months. Follow-up was 436 ± 90 days for all surviving patients. No patient suffered a relapse during follow-up, but three older patients (> 70 years old) developed drug-induced hepatitis. They all recovered with modification of medication. Five patients died from sepsis and respiratory failure, and all of them had pulmonary TB with TB peritonitis. These patients had no difference in onset year, age and race (Table 2). Most of them 198
had abdominal symptoms (n = 4), smoking habit (n = 4) and drinking habit (n = 4), and underlying immunocompromised status (liver cirrhosis in 3, diabetes in 1, and uremia in 1). All of them had moderate to severe ascites.
Discussion Taitung is in southeastern Taiwan, and has a high burden of TB. Therefore, a high incidence of abdominal TB was anticipated. However, during the past 20 years, only 21 patients were diagnosed with abdominal TB at Mackay Memorial Hospital, J Formos Med Assoc | 2009 • Vol 108 • No 3
Abdominal tuberculosis in Southeastern Taiwan
Taitung Branch. Several factors were assumed to account for such a disproportionately low rate of abdominal TB. These included poor health knowledge, relatively low socioeconomic status, high rates of alcohol abuse, limited access to healthcare, and poor control of chronic disease, such as liver cirrhosis, heart failure or diabetes. Many patients may have died from complications associated with chronic disease before abdominal TB was diagnosed. In addition, abdominal TB may be overlooked because most patients’ clinical presentation is nonspecific. Therefore, the true number of cases of abdominal TB may have been underestimated in this study. Here, we revealed a male predominance, which differs from several previous studies.1,12,13 In contrast to two previous studies in western Taiwan,8,9 the majority of patients in the present study were Taiwanese aborigines (15 of 21, 71.4%) with high rates of alcohol consumption (10 of 15). This was more than the proportion of Taiwanese aborigines in Taitung (33.8%).14 Frequent and excessive drinking may result in liver cirrhosis, malnutrition and immunocompromised status, which could increase the infection rate of abdominal TB. The most common age group in the present study was 30–50 years, and the mean age was 50 years, which is younger than that in a study of extrapulmonary TB Taiwan from 1996 to 2003.6 Poor treatment compliance, low socioeconomic status, and limited access to health care may be the reason. In addition, according to the Department of Statistics, Ministry of the Interior, Taiwan, in 2007,14 the average age of the aborigines (31.8 years old) was younger than that of the whole population (36.9 years old), which may be another reason. Liver cirrhosis was the most common underlying disease, which is one of the risk factors of TB peritonitis.4 In previous studies, TB peritonitis commonly occurred in patients with cirrhosis of the liver, especially that caused by alcoholism.15 Concurrent pulmonary involvement was noted in 11 patients, and this is consistent with two previous studies in Taipei, which showed 69–81% coexistent pulmonary TB.8,9,15 However, only one of these 11 patients admitted J Formos Med Assoc | 2009 • Vol 108 • No 3
a past history of pulmonary TB or a family history of TB. Therefore, a chest X-ray for demonstration of coexistent pulmonary TB might be important for further diagnosis. In agreement with previous studies,8,9 the most frequent presentation was abdominal pain, followed by fever, ascites, weight loss, abdominal distension, fatigue, anorexia, diarrhea, and anemia. Nevertheless, these nonspecific symptoms did not help in the diagnosis of abdominal TB. Moreover, laboratory, radiologic, endoscopic, laparoscopic, bacteriologic or histopathologic findings did not afford a rapid and reliable diagnosis. It took about 48 days to establish the final diagnosis, which significantly delayed treatment, and increased the rate of morbidity and mortality. Three steps to assess the diagnosis of abdominal TB are recommended.16 Clinical and radiologic findings are the first two steps for evaluation of suspected patients. The final step involves invasive techniques for obtaining tissue specimens, which are usually needed for final confirmation of the diagnosis. The most frequent site of abdominal TB has been demonstrated to be the gastrointestinal tract, according to two previous studies in Taipei.8,9 However, TB peritonitis was the most common finding in our series of patients. A high correlation with liver cirrhosis was noted in patients with TB peritonitis. In accordance with previous reports, the diagnosis in these patients was suspected from abdominal ultrasound and CT, with presentation of ascites and thickening of the mesentery and peritoneum.13,15–18 Laparoscopy with biopsy was the most reliable, safe and quick diagnostic method, as in previous studies.13,19,20 In our study, only two patients received this procedure, with a diagnostic rate of 100%. Perhaps laparoscopy should become the diagnostic tool of choice for patients presenting with the relevant background and clinical history. Gastrointestinal TB was noted in six patients, which mostly involved the ileocecal area, with ulceration, nodular pattern, and polypoid lesions, as described previously.8,9,19 Nonspecific manifestations were still noted however, without pathologic 199
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findings. The patient with disseminated TB initially presented with septic shock, but his condition improved after earlier triple therapy (isoniazid, rifampicin and ethambutol) and by an early pathologic finding from endoscopic biopsy. Two pelvic TB patients presented with a single pelvic mass, and one had peritoneal involvement as a result of a delay in diagnosis. As noted in previous studies,1,2,12,13,16,17 the prognosis of abdominal TB depends on prompt diagnosis and treatment. Most patients in our study showed a good response to anti-TB treatment, and no relapse occurred during long-term follow up. Additionally, there were no lasting complications which needed surgical intervention. However, in earlier studies from Taipei,8,9 a high proportion (> 70%) of patients with abdominal TB underwent surgical resection as a result of misdiagnosis. We noted hepatotoxicity in three older patients, but all of them improved after drug treatment modification. This was compatible with a previous study of extrapulmonary TB in Taiwan,6 which showed that the elderly are at greater risk of liver injury. Mortality rate was 24% in the present study, and in previous studies, it has ranged from 8% to 50%.1 All of the patients who died had TB peritonitis with pulmonary involvement and had underlying cirrhosis, which is one of the risk factors associated with higher mortality rates.1–3 There were only three Taiwanese aborigines in the mortality group, which suggests that mortality is not associated with race. Most of them had abdominal symptoms, smoking and drinking habits, and underlying immunocompromised status. The limitations of this study include its retrospective nature, incomplete examination in all patients, and inability to confirm an early diagnosis of abdominal TB. Clinical features, laboratory tests, and radiologic, endoscopic, bacteriologic and histopathologic findings do not provide clues for the early diagnosis of abdominal TB. Therefore, an algorithm of these diagnostic methods is needed to improve the diagnostic accuracy of this insidious disease. There is a necessity to increase the clinical awareness of this serious health 200
problem. A high index of clinical suspicion, along with the help of multiple adjuvant diagnostic tools, is required for correct diagnosis of abdominal TB. Abdominal TB is a relatively rare manifestation of extrapulmonary TB, even in Taitung, the TB epidemic area in Taiwan. The diagnosis should be considered in middle-aged men with alcoholic liver cirrhosis, who have nonspecific symptoms of abdominal pain, fever, ascites, weight loss, abdominal distension, and even symptoms of acute abdomen. Early diagnosis and effective treatment of abdominal TB may decrease morbidity and mortality.
Acknowledgments We are grateful to the surgery, radiology and pathology teams at Mackay Memorial Hospital, Taitung Branch.
References 1. Khan R, Abid S, Jafri W, et al. Diagnostic dilemma of abdominal tuberculosis in non-HIV patients: an ongoing challenge for physicians. World J Gastroenterol 2006;12: 6371–5. 2. Uygur-Bayramicli O, Dabak G, Dabak R. A clinical dilemma: abdominal tuberculosis. World J Gastroenterol 2003;9: 1098–110. 3. Sharma SK, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res 2004;120:316–53. 4. Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. Am Fam Physician 2005;72:1761–8. 5. The Global Competitiveness Report 2006–2007. World Economic Forum, 26 September 2006. 6. Hsu YC, Yang MH, Chen YH, et al. The epidemiology characteristics of extra-pulmonary tuberculosis in Taiwan, 1996–2003. Taiwan Centers for Disease Control 2007;23: 231–42. Available at https://teb.cdc.gov.tw/upload/doc/ 19592_The%20Epidemiology%20Characteristics%20of% 20Extra.pdf 7. Noertjojo K, Tam CM, Chan SL, et al. Extra-pulmonary and pulmonary tuberculosis in Hong Kong. Int J Tuberc Lung Dis 2002;6:879–86. 8. Chang HT, Lee S, Hsu H, et al. Abdominal tuberculosis: a retrospective analysis of 121 cases. Zhonghua Yi Xue Za Zhi (Taipei) 1991;47:24–30.
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9. Chen YM, Lee PY, Perng RP. Abdominal tuberculosis in Taiwan: a report from Veterans General Hospital, Taipei. Tuber Lung Dis 1995;76:35–8. 10. Centers for Disease Control, Taiwan. 2006 Annual Report: Communicable Diseases of Interest to the Public: Prevention of Tuberculosis (TB). 2006:47–51. 11. Centers for Disease Control, Taiwan. 2007 Annual Report: Communicable Diseases of Interest to the Public: Prevention of Tuberculosis (TB). 2007:51–6. 12. Uzunkoy A, Harma M, Harma M. Diagnosis of abdominal tuberculosis: experience from 11 cases and review of the literature. World J Gastroenterol 2004;10:3647–9. 13. Demir K, Okten A, Kaymakoglu S, et al. Tuberculous peritonitis: reports of 26 cases, detailing diagnostic and therapeutic problems. Eur J Gastroenterol Hepatol 2001;13: 581–5. 14. Department of Statistics, Ministry of the Interior, Taiwan. The General Situation of Taiwan Aborigines in 2007. Seventh Week Record of Department of Statistics, Ministry
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of the Interior, Taiwan, 2008. Available at http://www.moi. gov.tw/stat/index.asp Wang FK, Hsueh PR, Hung CC, et al. Tuberculous peritonitis: analysis of 35 cases. J Microbiol Immunol Infect 1998;31:113–8. Tanrikulu AC, Aldemir M, Gurkan F, et al. Clinical review of tuberculous peritonitis in 39 patients in Diyarbakir, Turkey. J Gastroenterol Hepatol 2005;20:906–9. Chong VH, Rajendran N. Tuberculosis peritonitis in Negara Brunei Darussalam. Ann Acad Med Singapore 2005;34: 548–52. Pereira JM, Madureira AJ, Vieira A, et al. Abdominal tuberculosis: imaging features. Eur J Radiol 2005;55: 173–80. Rai S, Thomas WM. Diagnosis of abdominal tuberculosis: the importance of laparoscopy. J R Soc Med 2003;96:586–8. Bernhard JS, Bhatia G, Knauer CM. Gastrointestinal tuberculosis: an eighteen-patient experience and review. J Clin Gastroenterol 2000;30:397–402.
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Abdominal Tuberculosis in Southeastern Taiwan: 20 Years of Experience Huan-Lin Chen,1 Ming-Shiang Wu,2 Wen-Hsiung Chang,3,4 Shou-Chuan Shih,3,4 Hsin Chi,4,5 Ming-Jong Bair1* Background/Purpose: Abdominal tuberculosis (TB) is a rare manifestation of extrapulmonary TB. This disease entity can be overlooked, and its early diagnosis is difficult because of its variable manifestations and lack of specific symptoms. Methods: The clinical and diagnostic features, treatment, and outcome of patients with abdominal TB at a major hospital in southeastern Taiwan from January 1987 to December 2006 were investigated. Results: Twenty-one patients with abdominal TB identified during the 20-year period were included. A predominance of male (13/21, 61.9%) and Taiwanese aborigine (15/21, 71.4%) patients was noted. Middleaged (30–50 years) patients with alcoholic liver cirrhosis had the highest risk. Common presenting features included abdominal pain (18/21, 85.7%), fever (16/21, 76.2%), ascites (13/21, 61.9%), and weight loss (12/21, 57.3%). The mean time to reach a diagnosis was 48 ± 10 days. Tuberculous peritonitis was noted in 11 patients, with a high correlation with liver cirrhosis (p = 0.0237, Fisher’s exact test). The other patients were diagnosed with TB of the gastrointestinal tract (n = 6), urinary tract (n = 2), and pelvis (n = 2). Abdominal sonography and abdominal computed tomography were helpful for diagnosis, by revealing ascites and thickening of the peritoneum. Pulmonary involvement was noted in 11 patients. Most of the patients (16/21, 76.2%) improved with anti-tuberculosis therapy, and five patients died from sepsis and respiratory failure. Conclusion: Abdominal TB is a rare manifestation of extrapulmonary TB, even in southeastern Taiwan where TB is prevalent. Delay in diagnosis is common and abdominal TB should be included in the differential diagnosis of middle-aged aborigine men with alcoholic liver cirrhosis and peritonitis. [J Formos Med Assoc 2009;108(3):195–201] Key Words: abdominal tuberculosis, extrapulmonary tuberculosis, gastrointestinal tuberculosis, tuberculosis, tuberculous peritonitis
cases are pulmonary TB.3 However, extrapulmonary organ involvement in TB is not uncommon. For human immunodeficiency virus (HIV)-negative patients, the frequency has been reported as 10–15%, in contrast to > 50% in HIV-positive patients.1–3 Abdominal TB is a rare manifestation
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It has been present in humans since antiquity and has become a major cause of death and disability in most parts of the world, especially in developing countries.1,2 The disease can affect multiple body systems, and most
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1
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, 2Division of Gastroenterology, Department of Internal Medicine, Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, 3Division of Gastroenterology, Department of Internal Medicine, and 5Department of Infectious Disease, Mackay Memorial Hospital, and 4Mackay Medicine, Nursing and Management College, Taipei, Taiwan. Received: June 18, 2008 Revised: September 9, 2008 Accepted: September 17, 2008
J Formos Med Assoc | 2009 • Vol 108 • No 3
*Correspondence to: Dr Ming-Jong Bair, Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, No. 1, Lane 303, Changsha Street, Taitung, Taiwan. E-mail: [email protected]
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of extrapulmonary TB, and a prevalence of around 3% has been noted previously.3 It may involve the gastrointestinal tract, peritoneum, mesenteric lymph nodes, genitourinary tract in the abdomen, or other solid organs (e.g. liver, spleen and adrenal glands).1,3,4 According to the Global Competitiveness Report 2006–2007,5 Taiwan ranks 60th on a worldwide scale in terms of the effectiveness of TB control. This means that TB control in Taiwan is still lagging behind that in other developed countries. A study of extrapulmonary TB in Taiwan, from 1996 to 2003 found that 23–27% of TB cases are extrapulmonary,6 which is similar to the rate found in Hong Kong in 1996.7 Two previous studies from Taipei Veterans General Hospital have demonstrated abdominal TB in 1991 and 1995.8,9 Surprisingly, a very high proportion of patients (74.1–79%) received laparotomy for diagnosis of abdominal TB at that time. These reports highlight the fact that abdominal TB is frequently misdiagnosed. Compared with western Taiwan, eastern Taiwan has a higher incidence and mortality rate of TB.10,11 In 2005, Taitung County, a southeastern province of Taiwan, had the highest mortality rate, with as many as 12.52 deaths per 100,000.10 It appears from these figures that Taitung is an epidemic area for TB in Taiwan. We conducted a retrospective study to collect information on the diagnostic features, clinical presentation, mycobacteriology, treatment, and outcome of abdominal TB over a 20-year period at Mackay Memorial Hospital, Taitung Branch, a major hospital in southeastern Taiwan.
Methods Patient information was obtained from the Mackay Memorial Hospital, Taitung Branch. We retrieved the records of all patients diagnosed with abdominal TB between January 1987 and December 2006. Patients were confirmed to have intra-abdominal TB (i.e. gastrointestinal tract, peritoneum, mesenteric lymph nodes, genitourinary 196
tract in the abdomen, or other solid organs, such as liver, pancreas or spleen). Patients who also had pulmonary involvement were considered for inclusion. Diagnosis of abdominal TB was based upon: (1) a positive acid-fast bacilli smear or culture; (2) histopathology showing tubercular granuloma (with or without caseation); (3) radiologic features compatible with tuberculosis on barium X-rays, ultrasound, or computed tomography (CT) of the abdomen; and (4) patients with a high index of clinical suspicion, with negative diagnostic workup, but who still showed a good response to a therapeutic trial with anti-TB agents.1 We collected details of demographics, clinical features associated with medical illness, and family and past history of TB. We recorded data on laboratory tests, chest and abdominal imaging, histopathology, acid-fast bacilli staining and culture, ascitic fluid analysis, upper gastrointestinal endoscopy, colonoscopy, laparoscopy and laparotomy. We also reviewed the clinical course of the disease and its complications. Additional epidemiologic and clinical information was obtained from detailed interviews conducted by telephone, using a standardized questionnaire. SPSS version 12.0 (SPSS Inc., Chicago, IL, USA) was used for data analysis. Descriptive analysis was performed for demographic, clinical and radiographic features.
Results Patient characteristics A total of 21 patients with abdominal TB were identified and included during the 20-year study period. Thirteen of these patients were male, and 15 were Taiwanese aborigines. Patient age ranged from 22 to 88 years, with a mean age of 50 ± 18 years. The most common age group was 30–50 years (Figure 1). Only two patients had a past medical history of pulmonary TB. History of other underlying diseases, such as liver cirrhosis (n = 7), renal failure (n = 4), diabetes (n = 1), and hypertension (n = 1), was recorded. There were also 12 patients who consumed excess alcohol and four J Formos Med Assoc | 2009 • Vol 108 • No 3
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7
Male Female
6 1
Number
5 4
5
2
1
1 0
2
3
3
0 0–10
0 11–20
1 21–30
2 31–40
41–50 51–60 Age (yr)
1
3
0 1
61–70
0 71–80
1 > 80
Figure 1. Age and gender distribution of patients with abdominal tuberculosis.
Table 1. Clinical symptoms of patients with abdominal tuberculosis (n = 21) Symptoms Abdominal pain Fever Ascites Weight loss Abdominal distension Fatigue Anorexia Diarrhea Ill-looking
n 18 16 13 12 10 8 8 4 2
patients who had a family history of TB. Abdominal pain was the most common symptom (n = 18) (Table 1). In addition, abdominal TB was found incidentally in three patients with: left ovary fibroma and TB peritonitis; pulmonary and bladder TB; and sigmoid diverticulitis with perforation and small bowel TB.
Diagnostic methods The average time to diagnosis was 48 ± 10 days. Abdominal ultrasound (n = 11) and CT (n = 10) were commonly used for diagnosis, which showed ascites and thickening of the peritoneum. Other abdominal investigations, such as gastroduodenoscopy (n = 4), colonoscopy (n = 1), barium examination (n = 2), and laparoscopy (n = 2) were less common. Ascites was present in 13 patients, but TB culture of ascites was positive in only five patients. Other positive TB culture included that of sputum, lower leg wound, mesenteric biopsy, J Formos Med Assoc | 2009 • Vol 108 • No 3
peritoneal specimen, and urine. Caseating granulomatous inflammation was found in 11 patients undergoing mass resection or endoscopic/ laparoscopic biopsy. Only one patient met the criterion of a good response to a therapeutic trial of anti-TB agents. Pulmonary TB was also found in 11 patients, including one with miliary TB and one with pleural effusion, and six of them were diagnosed with concurrent TB peritonitis. In addition, most of the patients had hypoalbuminemia (2.2 ± 0.8 g/dL; normal range, 3.5–5.0 g/dL) and anemia (9.9 ± 2.5 g/dL; normal range, 11–18 g/dL).
Location TB peritonitis was the most common diagnosis (n = 11, Figure 2). Six cases involved the gastrointestinal tract (3 cecum and terminal ileum, 2 small bowel, 1 esophagus and stomach). The patient with disseminated TB had esophageal, gastric, pulmonary, and lower leg wound involvement. He had alcoholic liver cirrhosis and diabetes and survived after anti-TB and antibiotic treatment. In addition, one of the patients also had peritoneal involvement, and another had orchiectomy because of testicular invasion. Two patients with pelvic mass and ovarian TB were diagnosed from surgical specimens, and one also had peritoneal involvement. Only two cases involved the urinary tract. One was diagnosed with TB from bladder pathology, and the other was confirmed by urine culture. Concurrent pulmonary TB was noted in 11 patients. 197
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Location GU tract, 2
Pelvis, 1
Pelvis + peritonium, 1
GI tract, 4
GI tract + peritonium, 2
Peritonium, 11
Figure 2. Predominant sites of involvement in abdominal tuberculosis (n = 21).
Table 2. Comparison of mortality factors
Onset year Sex Age (yr) Aborigine Symptoms Smoking Drinking Underlying disease Diagnostic method Ascites Pulmonary TB TB peritonitis Hemoglobin (g/dL) Albumin (g/dL)
Case 1
Case 2
Case 3
Case 4
Case 5
1990 F 32 Yes ABD pain Yes Yes Cirrhosis Echo No Yes Yes 15 1.4
1995 M 61 Yes Fatigue Yes Yes Cirrhosis CT AFB (+) Yes Yes 8.3 1.6
2000 M 58 No ABD pain Yes Yes Uremia Ascites from CAPD AFB (+) Yes Yes 8 2.3
2004 M 44 Yes ABD distension Yes No Cirrhosis Echo AFB (+) Yes Yes 9.6 2.9
2006 F 62 No ABD pain No Yes Diabetes Echo AFB (+) Yes Yes 9.8 1.1
ABD = abdominal; Echo = abdominal echo; CT = computed tomography; CAPD = continuous ambulatory peritoneal dialysis; AFB = acid-fast bacilli.
Treatment and outcome The clinical condition improved after anti-TB agents in 16 patients. Anti-TB treatment consisted of isoniazid, rifampicin, ethambutol, streptomycin and pyrazinamide in various combinations for 9–12 months. Follow-up was 436 ± 90 days for all surviving patients. No patient suffered a relapse during follow-up, but three older patients (> 70 years old) developed drug-induced hepatitis. They all recovered with modification of medication. Five patients died from sepsis and respiratory failure, and all of them had pulmonary TB with TB peritonitis. These patients had no difference in onset year, age and race (Table 2). Most of them 198
had abdominal symptoms (n = 4), smoking habit (n = 4) and drinking habit (n = 4), and underlying immunocompromised status (liver cirrhosis in 3, diabetes in 1, and uremia in 1). All of them had moderate to severe ascites.
Discussion Taitung is in southeastern Taiwan, and has a high burden of TB. Therefore, a high incidence of abdominal TB was anticipated. However, during the past 20 years, only 21 patients were diagnosed with abdominal TB at Mackay Memorial Hospital, J Formos Med Assoc | 2009 • Vol 108 • No 3
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Taitung Branch. Several factors were assumed to account for such a disproportionately low rate of abdominal TB. These included poor health knowledge, relatively low socioeconomic status, high rates of alcohol abuse, limited access to healthcare, and poor control of chronic disease, such as liver cirrhosis, heart failure or diabetes. Many patients may have died from complications associated with chronic disease before abdominal TB was diagnosed. In addition, abdominal TB may be overlooked because most patients’ clinical presentation is nonspecific. Therefore, the true number of cases of abdominal TB may have been underestimated in this study. Here, we revealed a male predominance, which differs from several previous studies.1,12,13 In contrast to two previous studies in western Taiwan,8,9 the majority of patients in the present study were Taiwanese aborigines (15 of 21, 71.4%) with high rates of alcohol consumption (10 of 15). This was more than the proportion of Taiwanese aborigines in Taitung (33.8%).14 Frequent and excessive drinking may result in liver cirrhosis, malnutrition and immunocompromised status, which could increase the infection rate of abdominal TB. The most common age group in the present study was 30–50 years, and the mean age was 50 years, which is younger than that in a study of extrapulmonary TB Taiwan from 1996 to 2003.6 Poor treatment compliance, low socioeconomic status, and limited access to health care may be the reason. In addition, according to the Department of Statistics, Ministry of the Interior, Taiwan, in 2007,14 the average age of the aborigines (31.8 years old) was younger than that of the whole population (36.9 years old), which may be another reason. Liver cirrhosis was the most common underlying disease, which is one of the risk factors of TB peritonitis.4 In previous studies, TB peritonitis commonly occurred in patients with cirrhosis of the liver, especially that caused by alcoholism.15 Concurrent pulmonary involvement was noted in 11 patients, and this is consistent with two previous studies in Taipei, which showed 69–81% coexistent pulmonary TB.8,9,15 However, only one of these 11 patients admitted J Formos Med Assoc | 2009 • Vol 108 • No 3
a past history of pulmonary TB or a family history of TB. Therefore, a chest X-ray for demonstration of coexistent pulmonary TB might be important for further diagnosis. In agreement with previous studies,8,9 the most frequent presentation was abdominal pain, followed by fever, ascites, weight loss, abdominal distension, fatigue, anorexia, diarrhea, and anemia. Nevertheless, these nonspecific symptoms did not help in the diagnosis of abdominal TB. Moreover, laboratory, radiologic, endoscopic, laparoscopic, bacteriologic or histopathologic findings did not afford a rapid and reliable diagnosis. It took about 48 days to establish the final diagnosis, which significantly delayed treatment, and increased the rate of morbidity and mortality. Three steps to assess the diagnosis of abdominal TB are recommended.16 Clinical and radiologic findings are the first two steps for evaluation of suspected patients. The final step involves invasive techniques for obtaining tissue specimens, which are usually needed for final confirmation of the diagnosis. The most frequent site of abdominal TB has been demonstrated to be the gastrointestinal tract, according to two previous studies in Taipei.8,9 However, TB peritonitis was the most common finding in our series of patients. A high correlation with liver cirrhosis was noted in patients with TB peritonitis. In accordance with previous reports, the diagnosis in these patients was suspected from abdominal ultrasound and CT, with presentation of ascites and thickening of the mesentery and peritoneum.13,15–18 Laparoscopy with biopsy was the most reliable, safe and quick diagnostic method, as in previous studies.13,19,20 In our study, only two patients received this procedure, with a diagnostic rate of 100%. Perhaps laparoscopy should become the diagnostic tool of choice for patients presenting with the relevant background and clinical history. Gastrointestinal TB was noted in six patients, which mostly involved the ileocecal area, with ulceration, nodular pattern, and polypoid lesions, as described previously.8,9,19 Nonspecific manifestations were still noted however, without pathologic 199
H.L. Chen, et al
findings. The patient with disseminated TB initially presented with septic shock, but his condition improved after earlier triple therapy (isoniazid, rifampicin and ethambutol) and by an early pathologic finding from endoscopic biopsy. Two pelvic TB patients presented with a single pelvic mass, and one had peritoneal involvement as a result of a delay in diagnosis. As noted in previous studies,1,2,12,13,16,17 the prognosis of abdominal TB depends on prompt diagnosis and treatment. Most patients in our study showed a good response to anti-TB treatment, and no relapse occurred during long-term follow up. Additionally, there were no lasting complications which needed surgical intervention. However, in earlier studies from Taipei,8,9 a high proportion (> 70%) of patients with abdominal TB underwent surgical resection as a result of misdiagnosis. We noted hepatotoxicity in three older patients, but all of them improved after drug treatment modification. This was compatible with a previous study of extrapulmonary TB in Taiwan,6 which showed that the elderly are at greater risk of liver injury. Mortality rate was 24% in the present study, and in previous studies, it has ranged from 8% to 50%.1 All of the patients who died had TB peritonitis with pulmonary involvement and had underlying cirrhosis, which is one of the risk factors associated with higher mortality rates.1–3 There were only three Taiwanese aborigines in the mortality group, which suggests that mortality is not associated with race. Most of them had abdominal symptoms, smoking and drinking habits, and underlying immunocompromised status. The limitations of this study include its retrospective nature, incomplete examination in all patients, and inability to confirm an early diagnosis of abdominal TB. Clinical features, laboratory tests, and radiologic, endoscopic, bacteriologic and histopathologic findings do not provide clues for the early diagnosis of abdominal TB. Therefore, an algorithm of these diagnostic methods is needed to improve the diagnostic accuracy of this insidious disease. There is a necessity to increase the clinical awareness of this serious health 200
problem. A high index of clinical suspicion, along with the help of multiple adjuvant diagnostic tools, is required for correct diagnosis of abdominal TB. Abdominal TB is a relatively rare manifestation of extrapulmonary TB, even in Taitung, the TB epidemic area in Taiwan. The diagnosis should be considered in middle-aged men with alcoholic liver cirrhosis, who have nonspecific symptoms of abdominal pain, fever, ascites, weight loss, abdominal distension, and even symptoms of acute abdomen. Early diagnosis and effective treatment of abdominal TB may decrease morbidity and mortality.
Acknowledgments We are grateful to the surgery, radiology and pathology teams at Mackay Memorial Hospital, Taitung Branch.
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