Ascitic tap showed spontaneous bacterial peritonitis with Gram negative organisms. He was started empirically on triple antituberculous treatment. (rifampicin ...
14 Berglund B, Hemmingson P. Effect of reinfusion of autologous blood on exercise performance in cross-country skiers. Int J Sports Med 1987;8:231-3. 15 Cadin DH, Kammerer RC, Hatton CK, Sekera MH, Merdink JL Analytical chemistry at the games of the XXlIIrd Olympiad in Los Angeles, 1984. Clin Chem 1987;33:319-27. 16 Park J. Doping test report of 1Oth Asian games in Seoul. J Sports Med Phys Fitness 1991;31:303-17. 17 Chan SC, Torok-Both GA, Billay DM, Przybylski PS, Gradeen CY, Pap KM, et al. Drug analysis at the 1988 Olympic Winter Games in Calgary. Clin Chem 1991;37:1289-96. 18 van der Merwe PJ, Kruger HS. Drugs in sport-results of the past 6 years of dope testing. South A,frMedJl 1992;82:151-3. 19 Perry HM, Wright D, Litdepage BN. Dying to be big: a review of anabolic steroid use. Brj Sports Med 1992;26:259-61. 20 McKillop G. Drug abuse in body builders in the west of Scotiand. Scott Med J 1987;32:39-41 21 Delbeke FT, Desmet N, Debackere M. The abuse of doping agents in competing body builders in Flanders (1988-1993). Int J Sports Med 1995;16:66-70.
22 Tricker R, O'Neill MR, Cook D. The incidence of anabolic steroid use among competitive bodybuilders. J Drug Educ 1989;19:313-25. 23 Whitehead R, Chillag S, Elliott D. Anabolic steroid use among adolescents * in a rural state.JFam Pract 1992;35:401-5. 24 Komoroski EM, Rickert VI. Adolescent body image and attitudes to anabolic steroid use. AmJDis Child 1992;146:823-8. 25 Terney R, McLain LG. The use of anabolic steroids in high school students. AmJDis Child 1990;144:99-103. 26 Windsor R, Dumitru D. Prevalence of anabolic steroid use by male and female adolescents. Med Sci Sports Exerc 1989;21:494-7. 27 Rickert VI, Pawlak-Morello C, Sheppard V, Jay MS. Human growth hormone: a new substance of abuse among adolescents? Clin Pediatr 1992;31:723-6. 28 Sports Council. Doping control in the UK A survey ofthe experiences and views of elite competitors. London: Sports Council, 1995. 29 Scarpino V, Arrigo A, Benzi G, Garattini S, La Vecchia C, Bernardi LR, et al. Evaluation of prevalence of "doping" among Italian athletes. Lancet 1990;336: 1048-50. 30 Lombardo J. Drug control programmes. BrJ Sports Med 1996;30:82-3.
Grand Rounds-Hammersmith Hospital Tuberculous enteritis A serious possibility in some patients Abdominal tuberculosis should always be considered in immigrants from regions where this disease is endemic who present with abdominal signs and symptoms. We describe the case of a young man from such a region with extensive tuberculous involvement of his gastrointestinal tract and peritoneum. This case highlights the difficulties in diagnosing tuberculous enteritis and the need to consider seriously the possibility of this disease in such patients. Tuberculous enteritis remains a challenge to the diagnostic acumen and therapeutic skills of both the physician and the surgeon.
Department of Gastroenterology, Hammersmith Hospital, London W12 OHS Case presented by: Farah B Ahmed, senior house officer in gastroenterology Chairman: J Scott, director of medicine Discussion group: H J F Hodgson, professor of gastroenterology C M Oakley, professor of cardiology J S Friedland, consultant in infectious diseases P W hId, consultant in
respiratory medicine Histopathology review: G Stamp, consultant in histopathology
Series editor: Dr S D Taylor-Robinson. BMJ 1996;313:215-7
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Case history A 25 year old Eritrean student, resident in Britain since 1989, first sought medical advice at this hospital in April 1994, when he was being investigated in relation to emigration to Canada. Plain chest radiography at this time was initially reported as showing a pulmonary nodule. On review, however, it was considered to be normal. He presented a year later to the gastroenterology department with large amount of weight loss (20 kg over a year), acid reflux, epigastric pain, intermittent vomiting, occasional bloody stools, and depression. He had no history of illicit substance misuse and no risk factors for HIV infection. He admitted having a very erratic eating pattern with poor nutritional intake. He was a non-smoker and did not drink alcohol. On examination he was extremely cachectic, weighing only 49 kg. He had a left sided proptosis and leukonychia, and he was clinically anaemic. Ascites was also present, but there was no lymphadenopathy, peripheral oedema, or chronic liver disease. Investigations showed a hypochromic, normocytic anaemia (haemoglobin concentration 99 g/l, mean corpuscular volume 84 fl), a low serum iron concentration (1.6 pmol/1), low transferrin concentration (0.85 g/l), low transferrin saturation index (7%), and raised ferritin concentration (367 pg/l). He had raised inflammatory markers (C reactive protein concentration 77 U/1, erythrocyte sedimentation rate 65 mm in the first hour) and a low serum albumin concentration (12 g/l). His total white cell count and remaining biochemical profile were normal. Blood and stool cultures were sterile and negative for acid fast bacilli. Chest radiography was unremarkable as were sigmoidoscopy, colonoscopy, and biopsies. Oesophagogastroduodenoscopy showed
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Results of investigations Test 24 Hour urinary protein Small bowel enema Computed tomography of abdomen Computed tomography of head Lumbar puncture Toxoplasma/cryptococcus/ herpes simplex virus Blood cultures including acid fast bacilli, Mycobacterium avium-intracellulare All virology tests including HIV-0,1,2 CD4:CD8 ratio Malaria films Strongyloides Autoantibodies including antineutrophil cytoplasmic antibody Bone marrow and blood film
Result Normal Normal Normal
Generalised cerebral atrophy Normal Negative
Negative
Negative Normal
Negative Negative Negative Reactive marrow with left shifted myeloid activity
oesophageal candidiasis, a benign gastric ulcer, mild duodenitis, and Helicobacterpylori infection. He was admitted for further investigations and treated with omeprazole, metronidazole, and amoxycillin for Hpylori. He became febrile and expressed paranoid delusions and increasing confusion. He was started on multivitamins and thiamine in view of his malnourished state. The working diagnosis was a chronic infectious aetiology, retroviral or tuberculous, with a broad differential of small bowel pathology or a protein-losing enteropathy. However, no acid fast bacilli were seen in either cerebrospinal fluid or peripheral blood, and no organisms were grown with standard culture techniques. Despite numerous investigations, including HIV tests, no positive results were obtained (box). Five days after admission he had a grand mal seizure and was started on phenytoin. A contrast enhanced computed tomogram of the head showed generalised cerebral atrophy with prominent ventricles and subarachnoid spaces; magnetic resonance imaging done before and after gadolinium enhancement suggested 215
diffuse brain stem swelling with no enhancing lesions. Ascitic tap showed spontaneous bacterial peritonitis with Gram negative organisms. He was started empirically on triple antituberculous treatment (rifampicin, isoniazid, and pyrazinamide) and also broad spectrum antibiotics and steroids. He continued to deteriorate, however, gradually becoming more confused and unresponsive. A few days later he had a massive gastrointestinal haemorrhage. Oesophagogastroduodenoscopy did not show any bleeding lesions. A visceral angiogram showed a bleeding jejunal ulcer; this was then embolised. A repeat ascitic tap two days later showed frank pus. During this procedure he became unresponsive and had a brief respiratory arrest, and he subsequently underwent an emergency laparotomy. At laparotomy 24 enteroenteric fistulas were found. Nodules of miliary tuberculosis, which were positive for acid fast bacilli on smear, were studded throughout the peritoneum. HISTOPATHOLOGY REVIEW
Several pieces of extremely distorted small intestine were received for examination. On the serosal surfaces there was organising fibrinous exudate, with abscesses that had necrotic caseous centres typical of tuberculosis in the mesenteric and omental fat specimens. Irregular perforated ulcers were found in the small intestine, which were not typical of the mucosal ulcerative form of tuberculosis, with some fibrosis and epithelial regeneration, which shows that they had been present for some time (fig 1). There were ill defined, poorly developed granulomas on the mucosa and evidence of ischaemia with organising thrombus and fibroblastic reaction. Some of the vessels were occluded by organised thrombus (fig 2). This must have been present for at least seven days, and therefore the embolisation procedure two days earlier is
Fig 1-Section of small bowel showing chronic ulcer with base of granulation tissue and fibrosis extending into the muscularis propria (single arrow). Note the well formed caseating granulomas on serosa with relatively sparse marginal lymphocytic reaction (double arrows)
Fig 2-Blood vessel in base of one of the ulcers showing luminal obstruction by fibrosis, with recanalisation
unlikely to have been the cause. Evidence of cytomegalovirus infection was also found (fig 3). The Ziehl-Neelsen stain was negative. No acid fast bacilli were found. It is well known, however, that the Ziehl-Neelsen stain is fairly insensitive unless large numbers of organisms are present. There are two possible explanations for the disseminated peritoneal tuberculosis with perforated mucosal ulceration. These ulcers may have initially been tuberculous, or this could be peritoneal tuberculosis associated with cytomegalovirus vasculitis, complicated by subsequent ischaemic damage and perforation. This is the preferred explanation. SUBSEQUENT HISTORY
The patient subsequently had another massive haemorrhage from the gastric arteries, which were then embolised. He remained in the intensive care unit for a further two and a half months, being nursed with an open abdomen and receiving blood products and nutritional support after more than 15 laparotomies. The wound was allowed to heal by secondary intention. Further sources of bleeding from breakdown of anastomoses and continual ulceration, despite antituberculous chemotherapy, omeprazole, and ganciclovir, continued to be identified during this time. He also developed a cytomegalovirus pneumonitis, from which he has since recovered. He made a slow, but steady recovery and regained all the weight that he had lost. The patient is now well, finishing his course of antituberculous treatment, and he leads a normal, active life in the Eritrean community in London. Comment Abdominal tuberculosis was common in Britain in the 18th and 19th centuries and early this century. During the 1 950s the recognition of Crohn's disease, the use of streptomycin and other drugs and the pasteurisation of milk led to the virtual disappearance of abdominal tuberculosis in the Western world.' In the past two decades the disease has reappeared. Common misconceptions that have led physicians to overlook the diagnosis are that abdominal tuberculosis is rare, that tuberculosis is a disease of poor people, that abdominal tuberculosis is always associated with active pulmonary tuberculosis, and that chronic abdominal pathology is synonymous with regional enteritis.' Abdominal tuberculosis is more common in the developing world. In India about 7% of hospital admissions for obstruction of the small bowel and about 6% of admissions for intestinal perforations are due to tuberculosis.3 The precise incidence of abdominal tuberculosis has not been determined. Old postmortem reports show that 70% of patients who die with pulmonary tuberculosis also have intestinal involvement.4
Fig 3-Blood vessel in base of one of the ulcers containing a probable endothelial cell (arrowed), with a nuclear inclusion typical of cytomegalovirus infection
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In a retrospective epidemiological study in the London Borough of Tower Hamlets of 163 900 people, 13 cases of abdominal tuberculosis were diagnosed; eight of these were in the Bangladeshi community. This gives a crude incidence of 7.7/100 000 a year in the Bangladeshi community, compared with 0.3/100 000 a year in white people. The highest age specific incidence was among those aged 16-20 years and 41-45 years.5 Other studies have shown similar data, with the average age of patients with abdominal tuberculosis being 31 years2 and the disease being more common in females.2 6 Clinical features include weight loss, general malaise and fatigue, anorexia, fever, diarrhoea, abdominal pain, abdominal masses, ascites, and peritonitis.6 Investigations show non-specific findings of anaemia,7 raised inflammatory markers, and increased concentrations of protein and lymphocytes in ascitic fluid.8 Plain abdominal radiographs show signs of intestinal obstruction in over 60% of cases,3 with contrast studies of small bowel and large bowel showing abnormal findings in 51% and 54% respectively.8 Laparoscopy is the investigation of choice for a quick diagnosis, as cultures of ascitic fluid are often negative6 and because it takes an average of six weeks for the results of tissue culture from endoscopic examination, which are positive in about 69% of cases.9 In addition, recent studies suggest that serological markers such as adenosine deaminase may be used as an easy, rapid, safe, and reliable routine method for early diagnosis of tuberculous ascites. Adenosine deaminase has 95% sensitivity and 98% specificity.10 Obstruction is the most common complication of abdominal tuberculosis, occurring in 30% of cases." Fistulas have been reported in 2-20% of cases,8 while perforations-which can be multiple and acute-occur in 5%.3 ' " It is interesting to note that perforations were rarely seen before the era of antituberculous chemotherapy; they seem to develop more frequently while the patients are taking antituberculous drugs.7 Intestinal bleeding" is also a recognised complication, although massive bleeding is rare.7 At present the most effective treatment of uncomplicated tuberculous enteritis is with drugs, with a 9-12 month course of antituberculous chemotherapy."2 Surgery is reserved for treating complications, and postoperative adjuvant chemotherapy is recommended. The prognosis for abdominal tuberculosis is poor, with an overall mortality of between 19% and 38%."
Discussion HJFH: This man came to us desperately ill, and we spent a week trying to establish the diagnosis of abdominal tuberculosis. He had lost a lot of weight, and he had non-specific evidence of immunosuppression in that he had oesophageal candidiasis and clearly some sort of infection, which took a week to diagnose. In trying to establish a diagnosis, we went down a lot of the traditional blind alleys in the diagnosis of abdominal tuberculosis; he had had small bowel radiography, which showed no evidence of small bowel tuberculosis, although he actually had it. When he deteriorated rapidly he was started on antituberculous chemotherapy; this rapid deterioration was probably at the time of his first perforation of the small bowel-that is certainly the implication from his ascitic fluid cultures. Then about 15 days after his antituberculous treatment had started, he deteriorated further, with bleeding and further gut perforations. Whether this was because of untreated tuberculosis or the bowel embolisation to stop his bleeding (which Dr Stamp has said is probably not the case) or because of cytomegalovirus is unclear.
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Dr Stamp has argued that cytomegalovirus may be the major contributing factor. Why did he develop cytomegalovirus infection? Was it because he was desperately ill, or was it because he was also started on steroids along with the antituberculous treatment? These are the questions highlighted by this case that are difficult to sort out. CMO: So is this man HIV positive? HJFH: No. He has had numerous tests, all of which gave negative results. JS: Nowadays, is abdominal tuberculosis caused by Mycobacterium bovis or M tuberculosis? HJFH: It can be caused by either, particularly in someone of this patient's background. In Britain it tends to be M tuberculosis. JSF: Most cases in sub-Saharan Africa also tend to be caused by M tuberculosis. A general point about patients with abdominal tuberculosis is that if they are HIV negative they tend to have poorer physical signs and less localising and more non-specific illness than patients with HIV. Characteristically, a lot of time is often spent looking for meningitis as the possible cause-as happened in this case-because it so difficult to determine the root of the illness. The other fascinating point about this case is the recurrent perforations, possibly due to the influx of the immune response or to the vasculitis associated with the cytomegalovirus. Also, he has unexplained cerebral atrophy despite being HIV negative. JS: If there is 97% homology between M tuberculosis and M bovis then why is there a species difference and apparent virulence difference? JSF: That is not known, but despite the homology the key genes are obviously making a large difference. PWI: It is always said that peritoneal biopsy is the way to diagnose these cases. Do you think that would have been very hazardous? The problem here is that the diagnosis was made much later than it might have been. HJFH: If one has multiple matted pieces of bowel, the process of performing a peritoneal biopsy at laparoscopy is itself hazardous. One of the reasons that I have preferred to do trials of antituberculous treatment in suspected abdominal tuberculosis rather than getting a definite diagnosis reflects an anecdotal experience with a 35 year old woman who underwent a laparoscopic approach; this turned into a laparotomy, during which she developed multiple perforations and subsequently died. I have therefore always felt that, other things being equal, a trial of antituberculous treatment is justified. The BMJ welcomes grand rounds from other hospitals. 1 Addison NV. Abdominal tuberculosis-a disease revived. Ann R Coll Surg Engi 1983;65:105-11. 2 Haddad FS, Ghossain A, Sawaya E, Nelson AR. Abdominal tuberculosis. Dis Colon Recan 1987;30:724-35. 3 Vaidya MG, Sodhi JS. Gastrointestinal tract tuberculosis: a study of 102 cases including 55 hemicolectomies. Clin Radiol 1978;29:189-95. 4 Scully RE, Galdabini JJ, McNeely BU. Case records of the Massachusetts General Hospital. NEnglJMed 1980;303:445-51. 5 Sheldon CD, Probert CS, Cock H, King K, Rampton DS, Barnes NC. Incidence of abdominal tuberculosis in Bangladeshi migrants in east London. 7lsber Lung Dis 1993;74:12-5. 6 Bastani B, Shariatzadeh MR, Dehdashti F. Tuberculous peritonitis-report of 30 cases and review of the literature. QJMed 1985;56:549-57. 7 Das P, Shukla HS. Clinical diagnosis of abdominal tuberculosis. Br J Surg
1976;63:941-6. 8 Sakai Y. Colonoscopic diagnosis of the intestinal tuberculosis. Mater Med
Pol 1979;11:275-8. 9 Voigt MD, Kalvaria I, Trey C, Berman P, Lombard C, Kirsch RE. Diagnostic value of adenosine deaminase in tuberculous peritonitis. Lancer 1989;1:751-4. 10
Shermnan 5, Rohwedder nJ, Raviktisjnan KP, Weg JG. Tuberculous enteritis
and peritonitis: report of 36 general hospital cases. Arch Intern Med 1980;140:506-8. 11 Tabrisky J, Lindstrom RR, Petera R, Lachman RS. Tuberculous enteritisreview of a protean disease. AmJ Gasnroenterol 1975;63:49-57. 12 Cookre NJ. Treatment of tuberculosis. BMJ 1985;291:497-8.
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