JRSM >
Volume 96, Number 6 >
Pp. 289-291
Department of Paediatric Gastroenterology, Chelsea and Westminster
Hospital, London
1 Department of Paediatric Infectious Diseases, Imperial College School of
Medicine, London, UK
Correspondence to: Dr Rajeev Gupta, Consultant Paediatrician, Barnsley District General Hospital, Gawber Road, Barnsley S75 2EP, UK E-mail: r.gupta{at}virgin.net
A link between deep vein thrombosis (DVT) and pulmonary tuberculosis has
been
described,1,2
but not with gastrointestinal
tuberculosis.
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CASE HISTORY
A 13-year-old girl from Afghanistan developed abdominal pain 3 days after arrival in the UK. The pain was moderate, generalized and initially not associated with fever or vomiting. She made several visits to the general practitioner, who found nothing specific on examination and prescribed analgesics. About a month later she had further severe pain now associated with fever and vomiting. At her local district general hospital she underwent appendicectomy, suppurative appendicitis and a faecolith being found at operation. Postoperatively the pain persisted, although much improved. Two months later she returned with pain in the right lower quadrant of her abdomen and the right lower limb. Doppler ultrasound showed thrombosis of the right femoral vein, extending to the internal iliac vein, and she was started on heparin. The abdominal pain continued and it was noted that she had lost 14kg over the previous four months. Further investigations revealed raised platelet count and C-reactive protein, macrocytic anaemia with low vitamin B12 and folate levels, but normal ferritin. Inflammatory bowel disease was suspected and she was referred to a tertiary hospital for further investigations and management. There was no history of past illness and no family history of chronic cough or gastrointestinal disease. The patient had received BCG vaccination at birth.
On arrival in the tertiary centre the main physical findings were a swollen and tender right thigh and leg and mild tenderness in the right iliac fossa. Liver function tests, serum amylase, urine and stool examination, and abdominal X-ray were all normal. Chest X-ray showed some peri-hilar shadows but not those typical of tuberculosis. A thrombophilia screen after stopping treatment was normal.
A Mantoux test showed pronounced erythema with induration of 10 x 30 mm. On colonoscopy the caecum was ulcerated and the terminal ileum was inflamed. Biopsy specimens showed severe active chronic inflammation with cryptitis and crypt abscesses. No caseation was seen. This was more consistent with Crohn's disease than with tuberculosis. Ziehl-Neelsen staining of endoscopy specimens was negative for acid and alcohol fast bacilli. Polymerase chain reaction for tuberculosis could not be done on endoscopic biopsy specimens since no standard controls for the assay are yet available for tissue diagnosis of tuberculosis. CT scanning of the abdomen showed thickened terminal ileum and caecum with lymphadenopathy. The scan also showed extension of the thrombus into the inferior vena cava.
Whether this child had tuberculosis or Crohn's disease or both was unclear. She was started on antituberculosis treatment without steroids but including isoniazid, pyrizinamide and rifampicin, together with ciprofloxacin since there was the possibility of her having consumed unpasteurised milk. A polymeric diet was also started to reduce inflammation. She improved symptomatically, gaining around 12kg with a decrease in sedimentation rate, C-reactive protein and platelets over the next 8 weeks.
Anticoagulation was difficult. The patient required low-molecular-weight heparin for some days and high doses of warfarin were needed to achieve a therapeutic international normalized ratio (INR). After several increases, 10mg per day kept the INR above 2. Repeat ultrasound at 8 weeks showed residual thrombus in the external iliac vein and common femoral vein with partial recanalization and flow around the thrombus. No clot was seen in the inferior vena cava or left iliac system. Repeat endoscopy after 8 weeks on the polymeric diet showed little change apart from mild narrowing of the terminal ileum. The polymeric diet was stopped and antituberculosis treatment was continued without steroids. Finally at 11 weeks the tissue specimen from the pretreatment endoscopic biopsy grew Mycobacterium tuberculosis. The plan is to continue antituberculosis treatment for one year.
COMMENT
The thrombogenic potential of tuberculosis is not well known and can have serious consequences. Activation of endothelial cells occurs in response to numerous physiological stimuli and results in the expression of endothelial proteins that change the normally non-thrombogenic internal surface of the vessel into a thrombogenic surface with subsequent development of local thrombosis. This process is described in pulmonary tuberculosis3 but not, we think, in gastrointestinal tuberculosis. Priming of vascular endothelium as a result of interaction between mycobacterial products and the host monocyte-macrophage system, which then synthesizes large amounts of tumour necrosis factor alpha and interleukin-6, has been postulated.4 Widespread disturbance in homoeostasis could focus on vascular intima that is activated and rendered more thrombogenic by proinflammatory cytokines.5 Additionally these cytokines induce hepatic acute phase responses7 that alter the levels of coagulation proteins.6
In the present case we must consider the possibility that venous thrombosis was a postoperative complication after appendicectomy. However, it did not develop until two months later, and she had been well mobilized soon after operation.
Why the difficulty with oral anticoagulation? This may have been related to the underlying disease process but another factor could have been the induction of hepatic enzymes by the antituberculosis drugs. The additional risk of thromboembolism with some common antituberculosis drugs leads to a dilemma. Increased risk of venous thromboembolism is described with rifampicin.2 In theory, both isoniazid and rifampicin can exacerbate the thrombogenic potential by killing the mycobacteria and enhancing release of interleukin-6 from peripheral blood mononuclear cells.7
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