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Journal of Gastroenterology and Hepatology (1999) 14, 723–729 found to be very useful in diagnosing colonic tubercu- losis. 2–5,17–22 This report describes the clinical features, colonoscopic and histological findings as well as man- agement of 50 cases of colonic tuberculosis seen between 1989 and 1995. METHODS Between 1989 and 1995, 50 patients with colonic tuber- culosis underwent colonoscopy. Colonoscopy was carried out after preparation with 10% mannitol using Olympus CF 20 L model colonoscope (Olympus Optical Co., Tokyo, Japan). The site and nature of INTRODUCTION Colonic tuberculosis, although uncommon, is not rare in India 1–5 and is by far the most common granuloma- tous disease of the colon. In recent years, there has been an increase in the number of cases of tuberculosis, even in the United States, mainly in Hispanics, black Americans, immigrants and refugees and in patients in- fected with human immunodeficiency virus (HIV) 6–13 and, therefore, clinicians in the USA and other devel- oped countries may also expect to see cases of colonic tuberculosis. The clinical manifestations of colonic tuberculosis are non-specific 1,5,14,15 as are the radi- ological findings 16 and, often, the diagnosis is made at surgery. 14,15 In recent years, colonoscopy has been ENDOSCOPIC DIAGNOSIS AND THERAPEUTICS Colonic tuberculosis: Clinical features, endoscopic appearance and management SRI PRAKASH MISRA,* VATSALA MISRA, MANISHA DWIVEDI* AND SURESH C GUPTA Departments of *Gastroenterology and Pathology, Moti Lal Nehru Medical College, Allahabad, India Abstract Background: Although rare in the West, colonic tuberculosis is not an uncommon disease in devel- oping countries. However, the clinical manifestations and radiological appearance of the disease are non-specific. In recent years, colonoscopy has been found to be very useful in diagnosing patients with colonic tuberculosis. Methods: Clinical features, colonoscopic findings, histology and response to treatment were recorded in 50 patients with colonic tuberculosis. Results: Abdominal pain, fever, anorexia, weight loss and diarrhoea were the common symptoms. The colonoscopic features consisted of ulcers (92%), nodules (88%), deformed caecum and ileocecal valve (42%), strictures (25%), multiple fibrous bands (8%) and polypoid lesions (6%). Segmental tubercu- losis and lesions simulating carcinoma were seen in 22 and 16% of patients, respectively. Histological examination of the colonic biopsy specimens showed well-formed, non-caseating granulomas in 18%, collection of loosely arranged epithelioid cells in 40% and chronic non-specific inflammatory changes in 42% of the patients. Six patients needed surgical intervention. The other 44 patients responded well to anti-tuberculous therapy and became asymptomatic. Conclusions: It is concluded that colonoscopy is a useful method for diagnosing colonic tuberculosis. It is suggested that if the clinical picture and colonoscopic appearance are suggestive of tuberculosis and target biopsies reveal non-caseating granulomas, a collection of loosely arranged epithelioid cells, or even non-specific changes, then a therapeutic trial of anti-tuberculous drugs should be given and continued if there is clinical improvement. © 1999 Blackwell Science Asia Pty Ltd Key words: colon, colonoscopy, diagnosis, disease, histology. Correspondence: SP Misra, Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad 211 001, India. Email: <[email protected]> Accepted for publication 10 February 1999.

Colonic tuberculosis: Clinical features, endoscopic appearance and management

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Journal of Gastroenterology and Hepatology (1999) 14, 723–729

found to be very useful in diagnosing colonic tubercu-losis.2–5,17–22 This report describes the clinical features,colonoscopic and histological findings as well as man-agement of 50 cases of colonic tuberculosis seenbetween 1989 and 1995.

METHODS

Between 1989 and 1995, 50 patients with colonic tuber-culosis underwent colonoscopy. Colonoscopy wascarried out after preparation with 10% mannitol using Olympus CF 20 L model colonoscope (OlympusOptical Co., Tokyo, Japan). The site and nature of

INTRODUCTION

Colonic tuberculosis, although uncommon, is not rarein India1–5 and is by far the most common granuloma-tous disease of the colon. In recent years, there has beenan increase in the number of cases of tuberculosis, evenin the United States, mainly in Hispanics, black Americans, immigrants and refugees and in patients in-fected with human immunodeficiency virus (HIV)6–13

and, therefore, clinicians in the USA and other devel-oped countries may also expect to see cases of colonictuberculosis. The clinical manifestations of colonictuberculosis are non-specific1,5,14,15 as are the radi-ological findings16 and, often, the diagnosis is made atsurgery.14,15 In recent years, colonoscopy has been

ENDOSCOPIC DIAGNOSIS AND THERAPEUTICS

Colonic tuberculosis: Clinical features, endoscopic appearance andmanagement

SRI PRAKASH MISRA,* VATSALA MISRA,† MANISHA DWIVEDI* AND SURESH C GUPTA†

Departments of *Gastroenterology and †Pathology, Moti Lal Nehru Medical College, Allahabad, India

AbstractBackground: Although rare in the West, colonic tuberculosis is not an uncommon disease in devel-oping countries. However, the clinical manifestations and radiological appearance of the disease arenon-specific. In recent years, colonoscopy has been found to be very useful in diagnosing patients withcolonic tuberculosis.Methods: Clinical features, colonoscopic findings, histology and response to treatment were recordedin 50 patients with colonic tuberculosis.Results: Abdominal pain, fever, anorexia, weight loss and diarrhoea were the common symptoms. Thecolonoscopic features consisted of ulcers (92%), nodules (88%), deformed caecum and ileocecal valve(42%), strictures (25%), multiple fibrous bands (8%) and polypoid lesions (6%). Segmental tubercu-losis and lesions simulating carcinoma were seen in 22 and 16% of patients, respectively. Histologicalexamination of the colonic biopsy specimens showed well-formed, non-caseating granulomas in 18%,collection of loosely arranged epithelioid cells in 40% and chronic non-specific inflammatory changesin 42% of the patients. Six patients needed surgical intervention. The other 44 patients responded wellto anti-tuberculous therapy and became asymptomatic.Conclusions: It is concluded that colonoscopy is a useful method for diagnosing colonic tuberculosis.It is suggested that if the clinical picture and colonoscopic appearance are suggestive of tuberculosisand target biopsies reveal non-caseating granulomas, a collection of loosely arranged epithelioid cells,or even non-specific changes, then a therapeutic trial of anti-tuberculous drugs should be given andcontinued if there is clinical improvement.© 1999 Blackwell Science Asia Pty Ltd

Key words: colon, colonoscopy, diagnosis, disease, histology.

Correspondence: SP Misra, Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad 211 001, India.Email: <[email protected]>

Accepted for publication 10 February 1999.

the lesions were recorded. Eight to ten biopsies wereobtained from each patient from all the lesions and fixedin 10% formal saline. Sections (3–5 mm) were slicedfrom paraffin blocks and stained with haematoxylin andeosin for histological details and by the Ziehl–Neelsenstain for the presence of acid-fast bacilli. The histolog-ical sections were examined by two experienced pathologists.

The diagnosis of colonic tuberculosis was based on histological evidence: presence of acid-fast bacilli on histology; presence of caseating or non-caseating well-formed granuloma(s) consisting of Langhans’ giantcell with epithelioid cells with a peripheral cuff of lymphocytes; collections of loosely arranged epithelioidcells; associated active pulmonary tuberculosis; or by the absence of other disease on histological examination of the biopsy obtained from the coloniclesions, along with a good response to anti-tuberculoustreatment.

RESULTS

The mean age of the patients in this study was 34.7 ±14.8 years. None of the patients were positive for HIV infection. There were 27 males and 23 females.The clinical features of these patients are shown in

724 SP Misra et al.

Table 1. Thirteen patients were already receiving anti-tuberculous drugs for a period of 1–6 weeks, before theywere seen by us. Full-length colonoscopy could be per-formed in 43 patients (86%). In the remaining sevenpatients, the area proximal to the stricture could not bevisualized.

The colonoscopic findings are shown in Table 2. Thecaecum, ascending colon, transverse colon, descendingcolon and sigmoid colon were involved in 21, 18, 13,15 and three patients, respectively. Rectal involvementwas seen in only one patient. Two or more sites wereinvolved in 16 patients (32%). In eight patients (16%)the colonoscopic appearance mimicked that of a carci-noma (Fig. 1). Colonic tuberculosis without involve-ment of the ileocaecal area (segmental tuberculosis) wasseen in 11 patients (22%). Nodules were 2–5 mm indiameter and had a yellowish (Fig. 2) or hyperaemicsurface. They were seen mostly in clusters, but were also seen in isolation. Ulcers were transverse and werecovered with milky white or yellowish exudate. Polypoidlesions were noted in three patients. Nodules and ulcerswere also seen in the strictured area (Fig. 3). Multiplefibrous bands scattered randomly and forming pocketswere seen in four patients (Fig. 4). A deformed ileocae-cal valve and caecum was present in 21 patients (42%;Fig. 5).

Histology

In 9 patients (18%), histological examination of targetcolonic biopsies revealed well-formed granulomas con-sisting of collection of epithelioid cells with Langhans’giant cells and a peripheral cuff of lymphocytes (Fig. 6).All the four patients with multiple fibrous bands showed

Table 1 Clinical features and laboratory findings

Symptoms, signs and investigations n %

Abdominal pain 38 76Anorexia 38 76Fever 38 76Weight loss 37 74Diarrhoea 28 56Vomiting 18 36Abdominal mass 14 28Alternating diarrhoea and constipation 7 14Frank bleeding per rectum 5 10Elevated erythrocyte sedimentation rate 46 92Anaemia 42 84Positive tuberculin test (n = 40) 29 72.5Positive chest X-ray 14 28

Table 2 Colonoscopic appearance in patients with colonictuberculosis

Colonoscopic findings n %

Ulcers 46 92Nodules 44 88Deformed ileocaecal valve and caecum 21 42Strictures 12 24Multiple fibrous bands 4 8Polypoid lesions 3 6

Figure 1 Colonic tuberculosis simulating neoplasia.There isa mass in the descending colon narrowing the colonic lumen.Note the presence of nodularity and ulceration.

the presence of well-formed granulomas. In 20 patients(40%), although well-formed granulomas were notpresent, colonic biopsy revealed a collection of looselyarranged epitheloid cells without the presence of Langhans’ giant cells (Fig. 7). In the remaining 21patients (42%), the histological examination revealedonly chronic non-specific changes in the form of pres-ence of chronic inflammatory cells in the lamina propria

Colonic tuberculosis 725

(Fig. 8). Five of these 21 patients had evidence of activepulmonary tuberculosis on chest X-ray. The re-maining patients were started on anti-tuberculous drugson a trial basis and the treatment was continued whenthey showed clinical improvement. Eight (50%) of these 16 patients had a positive tuberculin test. Noneof the biopsy specimens showed presence of acid-fastbacilli.

Figure 2 Colonoscopic appearance of nodules in a patientwith colonic tuberculosis. Figure 3 Stricture in a patient with colonic tuberculosis.

Note the presence of ulcer (arrow) and nodule (arrow head).

Figure 4 Randomly arranged fibrous bands formingpockets. Note that there is also a polypoid mass with ulceration.

Figure 5 Deformed ileocaecal valve and caecum in a patientwith ileocaecal tuberculosis.

Treatment

Patients were treated with rifampicin, isoniazid, etham-butol and pyrazinamide for a period of 2 months andthereafter received rifampicin and isoniazid for a furtherperiod of 10 months.

Clinical course and follow up

Six (12%) of the 50 patients needed surgical interven-tion; two each due to massive rebleeding, ileocaecalobstruction that did not respond to conservative treat-ment and colonic obstruction due to strictures in thecolon. Histological examination showed presence of

726 SP Misra et al.

caseating granulomas in all six and acid-fast bacilli infour of the six resected specimens. Colonoscopic biop-sies had shown non-specific inflammatory changes infive and collection of loosely arranged epithelioid cellsin one of these patients. The remaining 44 patientsresponded well to anti-tuberculous drugs and becameasymptomatic. The clinical course and response tovarious histological lesions is shown in Table 3.

Repeat colonoscopy was performed in 36 patients,including all 10 with strictures (two patients with stric-tures were operated), 1–3 months after completion ofthe treatment. In 30 cases, the colonoscopic abnormal-ities had disappeared. In the remaining six, the stric-tures had opened considerably, but not fully.

Figure 6 Well formed epithelioid granuloma with Lang-hans’ giant cells and peripheral cuff of lymphocytes in thecolonic mucosa of a patient with colonic tuberculosis.

Figure 7 Colonic biopsy showing loosely arranged epitheli-oid cells.

Table 3 Active pulmonary tuberculosis and response to anti-tuberculous therapy in relation to the histological changes seen inthe study

Histological findings n Active pulmonary TB (n) Response to ATT

Well-formed granuloma(s) 9 5 All responded wellLoosely arranged epithelioid cells 20 4 One operated, others responded wellNon-specific inflammatory changes 21 5 Five operated, others responded well

TB, tuberculosis; ATT, anti-tuberculous therapy.

DISCUSSION

The incidence of tuberculosis is rising, both in theUnited States of America23 as well as in the UK.24,25

Since 1985, the number of cases has increased by 16%in the USA, with almost 26 000 cases reported in 1990alone.23 In the USA, tuberculosis occurs primarily inpatients with acquired immunodeficiency syndrome, inimmigrants, in the urban poor, in native Americans onreservations, in prisoners and in the elderly.6,8,26,27 Fol-lowing the resurgence of tuberculosis, there have beentwo recently published series of patients with ab-dominal tuberculosis in the United States.9,28 Articleswarning clinicians to be aware of abdominal tuberculo-sis have been published in other developed countries aswell29,30 and, therefore, clinicians in the developed coun-tries are more likely to encounter patients with colonictuberculosis now, than in the past.

The problem with colonic tuberculosis is that, despitea high index of suspicion, it is difficult to diagnose.Theclinical symptoms and signs are non-specific and, moreimportantly, search for another foci of active tubercu-losis in the lungs is not helpful as only approximatelyone-quarter of patients with intestinal tuberculosis haveevidence of active pulmonary tuberculosis. Althoughradiolographic studies may be useful, they are not specific.31

Colonic tuberculosis 727

The colonoscopic features described in patients with colonic tuberculosis are transverse or linear ulcers,nodules, deformed ileocaecal valve and caecum andpresence of inflammatory polyps.2,3,5,17 In addition tothe above-mentioned features, in four of the presentpatients, multiple fibrous bands arranged in a haphaz-ard fashion, forming pockets were seen. Such findingshave not been described by most investigators.2–4,17–22

However, Singh et al., in a recent study, noted similarfindings in five of their patients.5 An interesting obser-vation in the present study was that all the four patientshaving fibrous bands at colonoscopy, showed presenceof well-formed granulomas on histological examinationof the biopsied tissue.

It has been noted that in colonic tuberculosis, thecaecum is the most commonly affected site.2,3,5,32 Thisis probably due to the relative stasis and presence oflarge aggregates of lymphoid tissue in that area. In this study, too, the caecum was the most common site of involvement (42%). Involvement of the colonwithout involvement of the ileocaecal area (segmentaltuberculosis) was seen in 22% and colonic lesions mimicking carcinoma were seen in 16% of our patients.Similar colonoscopic findings have been reportedearlier.3,5,33,34

Frank bleeding from colonic tuberculosis was seen infive of our patients. Two of these subsequently had tobe operated on because of massive rebleeding. Althoughminor rectal bleeding is known to occur frequently,5,13

major bleeding has only occasionally been reported inpatients with colonic tuberculosis.35–37

In the present study, well-formed granulomas wereseen in only 18% of the patients, but caseation was notseen in even a single case. It is well known that granu-lomas may not be seen in mucosal biopsies of nodules,ulcers or other lesions because they are mostly locatedin the submucosa of the tissue.9,38–40 Caseation may beabsent or be present only in the lymph nodes1,2,39 andmay not even be found in patients who have receivedanti-tuberculous treatment in the past.1 Thirteen (26%)of our current patients were already receiving anti-tuberculous therapy for suspected tuberculosis beforebeing seen by us. However, in this study, caseating granulomas were seen in the resected specimens of allsix patients who were operated on.

It may be that, due to the widespread availability ofcolonoscopy, the diagnosis of colonic tuberculosis isbeing made earlier and, therefore, the classical featuresof colonic tuberculosis, including caseation, are notseen. This is borne out by a comparison of the earlierstudies with the more recent ones. While caseation wascommonly seen in the earlier studies,1,2 it was uncom-mon in the later studies.3–5 We believe that this wouldbe the trend in future studies too.

None of the biopsy specimens obtained by colono-scopic examination showed presence of acid-fast bacilli.Acid-fast bacilli have been reported in 50–100% ofspecimens from patients with intestinal tuberculo-sis,21,41–43 but there are several reports where acid-fastbacilli could not be detected on histological examina-tion of the biopsy material.2,3,5,17,19 Acid-fast bacilli were,however, seen in four of the six specimens obtained atsurgery.

Figure 8 Non-specific inflammation of the lamina propriaby chronic inflammatory cells.

In previous studies, culture of the tissue obtained bycolonoscopic biopsy have grown Mycobacterium tuber-culosis in 6–69% of cases.2–4,43 Although culture is thehallmark for diagnosis, it is not reliable in patients withactive pulmonary tuberculosis, where it may yield afasle-positive result because of the swallowed sputum.Culture sensitivity may be used, however, to determinethe sensitivity of the bacilli to drugs. This is becomingimportant because of the emergence of drug-resistantstrains.31 We did not attempt culture of the organism,because an earlier study from our center did not get agood yield of the organism by culture, even from surgi-cally obtained intestinal tissue; although the yield wasgood when the material for culture was obtained fromthe mesenteric lymph nodes.44 In another recent study,of the 62 patients studied, culture did not grow M.tuberculosis in even a single case.5

It has been suggested that if there is a high clini-cal suspicion of colonic tuberculosis, anti-tuberculouschemotherapy may be started on the basis of thecolonoscopic appearance alone.4,5 However, we wouldadvise a more cautious approach, and would suggestthat if the clinical and colonoscopic features are sug-gestive of colonic tuberculosis and multiple target biop-sies do not show evidence of any other disease, then atherapeutic trial of anti-tuberculous drugs can safely begiven to these patients. A recent review article has givena similar recommendation.31

In conclusion, this study has shown that the clinicalfeatures of colonic tuberculosis are non-specific andmost frequently are abdominal pain, anorexia, fever and weight loss. The colonoscopic appearances includeulcers, nodules, deformed ileocaecal valve and caecum,strictures with nodularity and ulceration and multiplefibrous bands spreading in a haphazard fashion. Lesionsmimicking neoplasia, massive rectal bleeding, multiplesite involvement, polypoid lesions and segmental tuber-culosis also occur. Colonoscopic biopsy is helpful byeither making a positive diagnosis or at least by ex-cluding other diseases that simulate the colonoscopicappearance of tuberculosis. It is suggested that thereshould be a high clinical suspicion of tuberculosis andif the clinical picture and colonoscopic appearance aresuggestive of colonic tuberculosis and target biopsiesreveal caseating or non-caseating granulomas or non-specific chronic inflammatory cells in the laminapropria with no evidence of other disease, then a thera-peutic trial of anti-tuberculous drugs should be givento such patients and should be continued if there is agood clinical response.

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