Gut, 1964, 5, 524

Ileo-caecal tuberculosisJ. S. HOWELL1 AND P. J. KNAPTON2

Fr-om the Birmingham United Hospitals and the Department of Pathology,University of Birmingham

EDITORIAL SYNOPSIS Seven patients with proven ileo-caecal tuberculosis and six others in whom thepresumptive evidence of intestinal tuberculosis was very strong were admitted to the UnitedBirmingham Hospitals in the period 1951-62. The features of the condition are described, and thedifficulties of diagnosis, both clinical and pathological, are discussed. Any lesion of the bowelshowing follicular lesions with giant cells should be carefully searched for tubercle bacilli.

Tuberculous ulceration of the intestine has beenrecognized from antiquity as a serious complicationof advanced pulmonary tuberculosis. In India, Ukil(1942) found that of 1,000 cases of intestinaltuberculosis 95% were secondary to the pulmonarydisease. In western countries in recent years thisform of intestinal tuberculosis has become un-common, probably due to the more effective controlof tuberculosis, and Mitchell and Bristol (1954)found intestinal complications in comparatively fewpatients with pulmonary tuberculosis.

Ileo-caecal tuberculosis without apparent lungdisease was frequently diagnosed in the earlier partof this century but the diagnosis has been made lessoften since Crohn, Ginsburg, and Oppenheimer(1932) described the entity of regional ileitis. Bothconditions involve the region of the terminal ileumand are grossly, and sometimes microscopically,similar. Hence papers on ileo-caecal tuberculosispublished before Crohn's original contribution areopen to considerable doubt unless accompanied bybacteriological proof. Since 1932 case reports ofileo-caecal tuberculosis have been few and allsuggest that the condition is distinctly uncommon, atleast in the western hemisphere (Hoon, Dockerty,and Pemberton, 1950; Fridjohn and Ellis, 1957;Paustian and Bockus, 1959) and some observershave doubted the existence of this entity (Warrenand Sommers, 1948). In India the condition appearsto be much more common (Anand, 1956), a pointof some importance in the context of the presentpaper.

Interest in ileo-caecal tuberculosis was stimulatedbythe study ofa bacteriologicallyproven case (A.M.).Subsequently an investigation was undertaken to' Present address: Pathology Department, Poole General Hospital,Poole, Dorset;Present address: Plymouth General Hospital, Devon

assess the frequency and to study the clinical andpathological features of tuberculous lesions of thebowel situated at, or in fairly close proximity to,the ileo-caecal valve, among patients admitted to theUnited Birmingham Hospitals during the 12-yearperiod 1951-62, and on whom laparotomy orresection of bowel had been performed.

MATERIAL

In 12 cases a diagnosis of tuberculosis had been madeafter histological examination of resected portionsof bowel. In a further patient a hypertrophic bowellesion with constriction was found at laparotomy butwas not resected; other collateral evidence for thetuberculous nature of this lesion was very strong.

In seven of the 12 resected specimens bacterio-logical proof of the disease was obtained either bydemonstrating alcohol-acid-fast bacilli in the tissuesections (five cases) or by culture (two cases). Theremaining five cases had histological features,discussed later, which made a diagnosis of tubercu-losis highly probable, but in the absence of bacterio-logical proof by no means certain.

CLINICAL FEATURES

The 13 patients consisted of 10 men and threewomen whose ages varied at diagnosis from 24 to62 years. Six men and one woman were immigrantsfrom India or Pakistan, but the length of time spentin England was not recorded in all cases. Languagedifficulties made taking adequate histories difficultin certain instances. The most frequent symptom(Table I) was a constant, dull, aching abdominalpain, which was present in 11 patients. In five it wassituated either in the central abdomen or in theright iliac fossa. In five, the onset of abdominal

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Jleo-caecal tuberculosis

TABLE ISYMPTOMS AND SIGNS

Symptonts andl Sign.s

GastrointestinalAbdominal painVomitingAbdominal distensionAbdominal massAnorexiaDiarrhoeaConstipationAlternating diarrhoea and constipationWindPost-prandial painMelaenaFistulae

GeneralWeight lossAnaemiaWeaknessNight sweats

862l

pain was sudden, with vomiting and other mani-festations of acute intestinal obstruction. Threepatients had diarrhoea, two constipation, and afurther two diarrhoea alternating with constipation.In eight there was a variable degree of weight lossand in two this was the major complaint.A mass in the right iliac fossa was found in five

patients. Six were suffering from iron-deficiencyanaemia but only one patient had obvious melaena.Low fever was present in five patients when admittedto hospital.The following histories illustrate some of the

main clinical features in bacteriologically provencases.

CASE REPORTS

CASE S.T. An English woman of 62 presented with losscf weight, anorexia, and lassitude of eight months'duration. There were no abdominal symptoms. Physicalexamination revealed a fullness in the right iliac fossa.After occult blood had been found in the stools, a bariumenema showed deformity of the caecum and ascendingcolon thought to be due to a carcinoma. A chest radio-graph was normal. Laparotomy was performed and anoedematous mass involving the caecum and colon wasresected and an ileo-colic anastomosis performed. Sheremained well for 10 years without antituberculous drugsuntil 1961 when she became unwell with recurrence of amass in the right iliac fossa. This became progressivelysmaller when streptomycin, para-amino-salicylic acid,and iso-nicotinic acid hydrazide were prescribed, andshe apparently recovered completely.

CASE A.M. An English woman of 47 complained of lossof 2 st. in weight, epigastric discomfort, and lassitude forone year. Appetite remained good. A brief period ofdiarrhoea preceded admission to hospital, when examin-ation revealed wasting, anaemia, and a temperature of99°F. There was a diffuse tender mass in the right iliacfossa. Barium enema showed a lesion, possibly granulo-matous, involving the terminal ileum and caecum. Chestradiographs showed calcification at both hila and a lessdense shadow in the left mid zone; but these changes werenot considered to be tuberculous. At laparotomy theterminal ileum and caecum were thickened with smallnodules on the serosal surface; three other areas of ileumshowed the same changes and were resected togetherwith the caecum (Fig. 1). The mesentery was thickenedand the lymph nodes enlarged. After operation, andrepeated examinations, the sputum was found to containtubercle bacilli. She was treated with streptomycin, para-

S 4 5 4 7 a 9 10 I 1t2 1t 141A 16 17 18 1929 t.2 23 24 2526 27 28 24 30

FIG. 1. Caecum and terminal ileum showing ulceration and thickening of the caecum with appearances like those of-carcinoma. Note the two segmented lesions in the ileum showing thickening and ulceration.

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J. S. Howell and P. J. Knapton

amino-salicylic acid, and iso-nicotinic acid hydrazidewith slow resolution of the softer pulmonary shadow,disappearance of the abdominal symptoms, and a steadygain in weight.

CASE H.H. An English man of 42 complained of inter-mittent diarrhoea and constipation, sweating, and loss ofweight of six months' duration. Examination revealed alarge firm mass in the right iliac fossa which after x-rayexamination was considered to be a carcinoma of thecaecum. A right hemicolectomy was performed. A chestradiograph showed a diffuse miliary mottling buttubercle bacilli were not found in the sputum either ondirect examination or on culture. Streptomycin, para-amino-salicylic acid, and iso-nicotinic acid hydrazidewere given post-operatively and the lung changes and allabdominal symptoms resolved within six months.

CASE M.M. A Pakistani man aged 28 presented withattacks of abdominal colic and vomiting. He had beenadmitted to hospital on two previous occasions when adiagnosis of subacute intestinal obstruction had beenmade, but with resolution of symptoms no active treat-ment had been undertaken. A barium meal betweenattacks had shown a stricture in the terminal ileum. Onhis third admission with acute small bowel obstruction,laparotomy revealed in the terminal ileum three distinctareas of thickening and stenosis, the lesions being separ-ated by normal bowel; the lesions were resected. Chestradiographs showed soft opacities in both upper lobes,but no tubercle bacilli were identified or cultured fromsputum or stools. The lung lesions resolved after fivemonths' treatment with streptomycin, para-amino-salicylic acid, and iso-nicotinic acid hydrazide, and bowelsymptoms have not returned.

PATHOLOGY

MACROSCOPIC APPEARANCES In this retrospectivesurvey, the gross descriptions of resected specimens

. -l-- .l..

FIJ. 2. Cross section of caecum (left) and ileum (right)showing great thickening ofbowel wall with obscuration ofall layers. Note extension of the process into the attachedmesentery.

have been culled from the operative findings and thedescription of the specimen as received in thepathology laboratory (Table II). The appearanceswere similar whether or not tubercle bacilli weresubsequently identified.The caecum alone was involved in two cases, in

one of which tubercle bacili were found. Bothshowed great thickening of the bowel with rathersuperficial mucosal ulceration. The bowel wall wasreplaced, and its muscle layers obscured by grey orwhite friable tissue (Fig. 2) which in one caseextended into the attached mesenteric fat. In onespecimen small white subserosal nodules werepresent. In both, the mesenteric lymph nodes were

Case Sex Age Nationality Site ofLesion

TABLE IIRESECTIONS OF TIJBERCULOUS BOWEL

Pathology of Resected Bowel

Thickening Ulcer Stenosis Serosal Seg- Lymph- Acid-fastNodules mented adenopathy Bacilli

Lesions

Chest Acid-fastRadiograph Bacilli in

Sputum

+ - - - + + Normal+ - + - + - Tuberculosis+ + + - + + Tuberculosis

+ - - - + + Normal

+ - - + + - Normal

+ + + + + Tuberculosis +

+ + + + + Tuberculosis+ + - + + + Tuberculosis+ + - - + + Normal- + - + - Normal+ - + - - Normal+ + - + Tuberculosis

S.T.A.A.H.H.

G.D.

H.C.

A.M.

MM.P.D.M.S.F.D.P.S.M.E.

FMM

F

M

F

MMMMMM

624642

25

35

47

284424292534

BritishPakistaniBritish

Indian

British

British

PakistaniBritishPakistaniPakistaniIndianPakistani

Caecum +Caecum +Caecum +and ileumCaecum +and ileumCaecum +and ileumCaecum +and ileumIleum +Ileum +Ileum +Ileum +Ileum +Ileum +

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lleo-caecal tuberculosis

enlarged, and replaced by tissue similar to that whichinvolved the bowel wall. The appearances were thusvery similar to those of carcinoma.Both caecum and terminal ileum were involved

in four cases, in three of which tubercle bacilli wereidentified. All showed thickening of the bowel,mucosal ulceration, and one showed ileal stenosis.Small subserosal nodules were present in two, butall four had enlarged mesenteric lymph nodes. Theappearances of the caecum resembled carcinoma(Fig. 1).

In six cases the terminal ileum only was involved,and in three tubercle bacilli were found. The bowelwas thickened in all specimens (Fig. 2), and all butone showed mucosal ulceration, but in only twoexamples was the ulceration described as circum-ferential. Significant stenosis was present in five,lymph glands were enlarged in four, and smallsubserosal nodules present in one.The case in which the terminal ileum was involved

but which was not resected occurred in a Britishmale aged 59 and is not included in Table II. Thebowel was involved in a granulomatous inflam-matory reaction causing almost complete stenosis.As he was known to have active pulmonary tubercu-losis and also extensive ulceration of the anal canal,which on biopsy had been shown to contain largenumbers of tubercle bacilli, the presumptive evidenceof a tuberculous bowel lesion is very strong.

MICROSCOPIC APPEARANCES

BACTERIOLOGICALLY PROVEN CASES There wereseven cases in which acid alcohol-fast bacilli weredemonstrated either in the tissue sections or elsecultured from lymph nodes. The basic histologicalchanges were those of tuberculosis, with manyfollicular lesions characterized by epithelioid cells,giant cells of Langhans type, and a peripheral zoneof chronic inflammatory cells. The lesions weremainly in the submucosal and serosal layers andinvolvement of the muscle layers appeared to be arelatively late manifestation when the follicularlesions were undergoing coalescence. In someinstances sheets of epithelioid cells interspersed withmultinucleated giant cells and chronic inflammatorycells, constituting tuberculous granulation tissue,were a marked feature.

Caseation, though not a prominent feature, waspresent in all specimens, although sometimesprolonged search was required to find it. Fibrosisvaried in amount, but occasionally there was afairly brisk reaction around the follicles, and notinfrequently there were areas of focal fibrosisconsistent with partial healing. Usually there was afibroblastic reaction separating muscle bundles and

the serosal layer was thickened and fibrotic. Somespecimens showed pronounced oedema involving alllayers of the wall, but especially the submucosa, andthis combined with the fibrosis, the progressivenature of the tuberculous reaction, and the diffusechronic inflammatory cell infiltration which waspresent in all parts explained the great thickeningand hypertrophic appearance of the bowel wall.The oedematous mucosa showed superficial

ulceration which did not penetrate the muscle layers.In only one example were pseudo-polypi found.Very frequently there were sinus tracks filled withpolymorphs which burrowed from the mucosa intothe muscle layers. Endarteritis of submucosal vesselswas a prominent feature in many specimens andmight have been responsible for the mucosalulceration.

In general the lymph nodes showed a histologicalreaction more typical of tuberculosis than the bowellesion. Discrete follicular lesions, associated withepithelioid cells, giant cells, and caseation were moremarked than in the bowel. Most of the nodes fromall the specimens examined showed this reaction.

BACTERIOLOGICALLY NON-PROVEN CASEs The histo-logical features of these cases showed no majordifferences from those cases in which tubercle bacilliwere demonstrated. In every instance the bowel wallcontained granulomatous lesions with foci ofcaseation similar to those already described. Thereaction in draining lymph nodes was also similar.

In all 12 specimens prolonged search was made forother possible causative agents-amoebiasis, actino-mycosis, etc.-but none was ever found.

DISCUSSION

The finding of seven bacteriologically proven casesof tuberculosis of the ileo-caecal region togetherwith six other cases in which there was strongpresumptive evidence of tuberculosis during a 12-year period indicates that this condition is rare.Nevertheless it must be considered in the differentialdiagnosis of intestinal obstruction and carcinoma ofthe colon, especially in patients with abnormal chestradiographs and in the immigrant Indian population.The symptoms and signs of ileo-caecal tuberculosis

as encountered in this series (Table I) are sufficientlysimilar to those of regional ileitis as to make thedifferential diagnosis extremely difficult and in nocase was a pre-operative diagnosis of tuberculosismade.When the caecum is involved a mass can frequently

be felt; Anand (1956) reported this sign in 48% ofpatients and Paustian and Bockus (1959) in 65% ofpatients. A mass was present in six of the 13 cases in

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the present series pre-operatively, and was usuallypresumed to be neoplastic.Even at laparotomy the true aetiology was

obscure as was emphasized by the provisionaldiagnosis (when given) on the request form forpathological examination. When the ileum alone wasinvolved the operation diagnoses included regionalileitis, chronic granulomatous inflammation ofobscure origin, and in one case ileal sarcoma. In allbut one of the cases where the caecum was involved,the lesion was thought at operation to be neoplastic.Segmented lesions of the bowel, common in

regional ileitis, were present in five specimens in thepresent series (Fig. 1) and a further one was foundinvolving the colon, but this was not resected withthe main lesion. In most cases the bowel wasthickened with a reddened serosa and could bedescribed as showing hose-pipe thickening. Thethickening extended into and involved the adjacentmesentery. Minute subserosal nodules, enlarged softlymph nodes, adhesions between involved segmentsand adjacent structures, sometimes with a littleexcess fluid in the peritoneal cavity, were frequentlypresent. All these gross features are common to bothtuberculosis and regional ileitis.Thus it is virtually impossible to confirm the

diagnosis of intestinal tuberculosis without laparo-tomy and bowel resection followed by full histo-logical and bacteriological examination of thespecimen. The microscopic differentiation betweentuberculosis and regional ileitis also presentsconsiderable difficulties because several features arecommon to both conditions. Important points infavour of tuberculosis included the presence of largenumbers of follicular lesions, some undergoingcoalescence. In regional ileitis the follicular lesionstend to be scattered, small and few in number, butthis may depend upon the stage of the disease atwhich resection is performed. The presence ofcaseation is of importance in the diagnosis oftuberculosis, but it must be stressed that in thepresent series, even in those cases with bacterio-logical proof, caseation was not a prominent featureand frequently several sections had to be examinedbefore small foci were found. Of equal importancewas the presence in the draining lymph nodes, evenwhen these were not obviously enlarged, of folliculargranulomatous lesions which generally showed amore typical tuberculous reaction than did thebowel. Whilst it is recognized that there are veryrarely causes for caseation other than tuberculosis,nevertheless it is considered that intestinal lesionswith caseation, together with similar lesions indraining lymph nodes, is sufficiently characteristic togive considerable support to a diagnosis of tubercu-losis even in the absence of bacteriological proof.

It must also be stressed that although in one or twoexamples large numbers of tubercle bacilli werepresent, in others very prolonged search wasnecessary to find them. The amount of caseationbore no relationship to the ease with which thebacilli were demonstrated.

It is of great importance to determine whetherthe intestinal lesion is secondary to another tubercu-lous focus in the body. All the patients in the presentseries had chest radiographs and in seven there wasevidence of tuberculosis, the activity of which was indoubt, radiologically, and in only two cases weretubercle bacilli subsequently recovered from thesputum. One of the two with positive sputum wasthe patient who did not have a bowel resection. Insix patients chest radiographs were entirely normaland there was no evidence of tuberculosis elsewhere.This raises the difficult question of how the bowelbecomes involved in the absence of overt tuberculosisin some other site. It seems that spread from involvedlymph nodes in a retrograde fashion is a possibility.The more advanced tuberculous lesions in the lymphnodes compared with the bowel lend some supportto this suggestion.The peculiar histological appearance in the bowel

with the interplay of progressive tuberculous granu-lation tissue, oedema, and reactive fibrosis producinghypertrophy of the bowel without the extensivebreakdown of tissue as observed in tuberculosis inall other situations in the body appears to be acharacteristic of this form of the disease. It is notpossible to give any explanation for this, but it hasbeen suggested by Stewart (1928), writing beforeregional ileitis had been described, that it is due to ahigh degree of immunity to the tubercle bacillus, orinfection produced by small numbers of bacilli, orthat a relatively avirulent strain of the organism isinvolved.

Resection combined with antituberculous drugswould appear to be the treatment of choice for thiscondition because otherwise progressive fibrosis withaccentuation of the stenosis might occur as thelesions heal under the influence of antituberculouschemotherapy. In the present series completerecovery has occurred in all cases with great improve-ment in general well-being, and with resolution ofany pulmonary involvement present at the time ofdiagnosis. There have been no recurrences exceptfor one patient (S.T.) to whom no chemotherapy wasgiven at the time of initial diagnosis. The recurrenceresolved on appropriate chemotherapy.

Our grateful thanks are due to the members of theconsultant staff of the United Birmingham Hospitalsunder whose care these patients were admitted and whoreadily made their records available to us.

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Jleo-caecal tuberculosis 529

REFERENCES

Anand, S. S. (1956). Hypertrophic ileo-caecal tuberculosis in Indiawith a record of 50 hemicolectomies. (Hunterian Lecture.)Ann. roy. Coil. Surg. Engl., 19, 205-222.

Crohn, B. B., Ginsburg. L., and Oppenheimer, G. D. (1932). Regionalileitis. J. Amer. med. Ass., 99, 1323-1329.

Fridjohn, M. H., and Ellis, F. R. (1957). Primary tuberculosis of theintestine. Practitioner, 178, 477-479.

Hoon, J. R., Dockerty, M. B., and Pemberton, J. de J. (1950). Ileocecaltuberculosis including a comparison of this disease with non-specific regional enterocolitis and noncaseous tuberculatedenterocolitis. Int. Abstr. Surg., 91, 417-440.

Mitchell, R. S., and Bristol, L. J. (1954). Intestinal tuberculosis: ananalysis of 346 cases diagnosed by routine intestinal radio-graphy on 5,529 admissions for pulmonary tuberculosis.1924-49. Amer. J. med. Sci., 227, 241-249.

Paustian, F. F., and Bockus, H. L. (1959). So-called primary ulcero-hypertrophic ileocecal tuberculosis. Amer. J. Med., 27, 509-518.

Stewart, M. J. (1928). The pathology of intestinal tuberculosis.Tubercle (Edinb.), 9, 409-414.

Ukil, A. C. (1942). Early diagnosis and treatment of intestinaltuberculosis. Indian med. Gaz., 77, 613-620.

Warren, S., and Sommers, S. C. (1948). Cicatrizing enteritis (regionalileitis) as a pathologic entity. Analysis of one hundred andtwenty cases. Amer. J. Path., 24, 475-502.

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