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Appendiceal tuberculosis A 26-year-old Ugandan female patient presented with 1 month of right iliac fossa pain, worsening in the last three days. She reported vomiting, diarrhoea, fevers, night sweats and weight loss. She was diagnosed with human immunodeficiency virus (HIV) seven years ago and was initially treated with a few months course of antiretroviral medications. During her pregnancy 21 months ago, she was re-commenced on anti-retrovirals and achieved undetectable viral load. However, after giving birth 18 months ago, she ceased taking the medications. She lives with her brother, who is currently being treated for pulmonary tuberculosis (TB). However, she denied any cough or haemoptysis. On examination, she was febrile (T = 38.8°C), tachycardic (106/ min) with right iliac fossa tenderness. There were no generalized peritonitism. Blood test showed low haemoglobin of 74 g/L (range 115–150) and normal white cell count of 6.7 × 109/L (range 4–11). Her CD4 count was 0.20 × 109/L (range 0.35–2.63). Computed tomography (CT) showed dilated appendix and terminal ileum with prominent wall enhancement and surrounding fat stranding (Fig. 1). There were multiple necrotic lymph nodes in the central mesentery extending into the right iliac fossa, the largest being 9.2 × 2.5 cm. These imaging findings were suggestive of a diagnosis of tuberculosis appendicitis. During laparoscopic appendicectomy, there was inflamed appendix with some turbid purulent fluid in the pelvis (Fig. 2). The adhesion between the uterus and anterior abdominal wall was consistent with previous Caesarean section. There was no intra-abdominal miliary TB. Macroscopically, the inflamed appendix had focally nodular thickened wall. Microscopy revealed extensive mucosal ulceration and granulomas with some necrosis (Fig. 3). There were no mycobacteria identified with Ziehl–Neelsen or Wade–Fite stains. The tissue was sent for Mycobacterium tuberculosis and atypical

mycobacterial polymerase chain reaction (PCR). No acid-fast bacilli were detected in the patient’s sputum and intraperitoneal fluid. The mycobacterium culture was negative. Post-operatively, she was commenced on TB treatment (isoniazid, rifampicin, ethambutol, pyrazinamide and pyridoxine). She was discharged a few days later with infectious disease physician follow-up. In 2013, the World Health Organization reported ∼9 million people developed TB worldwide. Thirteen percent (1.1 million) of people who developed TB were HIV-positive. The African region accounts for about four out of every five HIV-positive TB cases and TB deaths among people who were HIV-positive.1 Gastrointestinal TB is a rare form of extrapulmonary TB. The ileo-caecum is involved in 40–75% of cases of gastrointestinal TB, whereas the appendix is involved in only about 2% of cases. TB appendicitis accounts for 0.6–2.9% of all appendicectomies.2 A prompt diagnosis relies on a high index of suspicion. Most patients present with chronic right iliac fossa pain, vomiting, diarrhoea, fever and weight loss.3 These may mimic symptoms of other chronic inflammatory diseases such as Crohn’s. Other presentations include features of acute appendicitis or perforation; and the latent incidentally detected disease.4 Abdominal CT demonstrates an inflammatory mass in the ileocaecal zone. The subtle distinction between acute bacterial and TB appendicitis is in the presence of asymmetrical thickening of ileocaecal valve, with concurrent enlarged rim-enhancing regional lymph node ascites and mesenteric thickening.5 Tuberculin skin test and chest radiography may initially be negative in up to 50% of patients.6 Intraoperative findings include diffuse inflammatory mass with tenacious adhesions and may involve terminal ileum, ileocaecal valve and the ascending colon.7 Histopathological examination is often the only way to diagnose appendiceal TB. Therefore, the commencement of treatment is often

Fig. 1. Computed tomography (left: coronal, right: axial) showing dilated thickened appendix (red arrow), thickened ileum (blue arrow) and multiple rim-enhancing mesenteric lymphadenopathy (yellow arrow).

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Although considered a rare entity, high index of suspicion for TB appendicitis is important, especially in immunocompromised migrants from TB-endemic area, with atypical history for acute appendicitis. Close cooperation between surgical, infectious disease and pathology teams is essential. Surgery is the primary treatment for TB appendicitis because drugs alone cannot control recurrent attacks of inflammation. Complications of the untreated TB appendicitis include lower gastrointestinal haemorrhage and enterocutaneous fistula, which can occur even several years following the appendicectomy.10

References

Fig. 2. Intraoperative photograph laparoscopic Inflamed, nodular thickened appendix.

appendicectomy.

Fig. 3. Histopathology of the appendix. The 10× objective (left) showed ulcerated appendiceal mucosa with underlying granulomatous inflammation comprising epithelioid and multinucleate histiocytes, and lymphocytes. The 20× objective (right) showed caseating granulomatous inflammation comprising central necrosis (arrowhead) surrounded by palisaded epithelioid histiocytes (solid arrowhead), including one multinucleate cell (arrow).

delayed until after surgery. A score of at least 4 out of 8 parameters was proposed to differentiate intestinal TB from Crohn’s disease: granulomas size (>400 μm) and number (>5 in one segment), Langhans giant cells, caseating necrosis, confluent or discrete granulomas, ulcers with bands of epitheloid histiocytes and perigranulomatous lymphoid cuffs.8 Microbiological diagnosis is difficult. Detection of acid-fast bacilli in biopsy specimen has low sensitivity (25–35%). Positive cultures for M. tuberculosis usually are after 4–8 weeks of incubation and are only positive in 30% of patients. TB PCR and QuantiFERON tests show better sensitivity.9

1. World Health Organization. Global Tuberculosis Report. Switzerland: WHO Press [PDF on Internet]. [Cited 2 Nov 2014.] Available from URL: http://www.who.int/tb/publications/global_report/en/ 2. Agarwal P, Sharma D, Agarwal A et al. Tuberculous appendicitis in India. Trop. Doct. 2004; 34: 36–8. 3. Jakubowski A, Elwood RK, Enarson DA. Clinical features of abdominal tuberculosis. J. Infect. Dis. 1988; 158: 687–92. 4. Singh MK, Arunabh, Kapoor VK. Tuberculosis of the appendix – a report of 17 cases and a suggested aetiopathological classification. Postgrad. Med. J. 1987; 63: 855–7. 5. Akhan O, Pringot J. Imaging of abdominal tuberculosis. Eur. Radiol. 2002; 12: 312–23. 6. Rasheed S, Zinicola R, Watson D, Bajwa A, McDonald PJ. Intraabdominal and gastrointestinal tuberculosis. Colorectal Dis. 2007; 9: 773–83. 7. Massalis I, Lampropoulos C, Efthymiou G, Papadima E. Multiple, large granulomas in a patient with extensive intestinal tuberculosis. BMJ Case Rep. 2012; doi: 10.1136/bcr-2012-007093. 8. Jin XJ, Kim JM, Kim HK et al. Histopathology and TB-PCR kit analysis in differentiating the diagnosis of intestinal tuberculosis and Crohn’s disease. World J. Gastroenterol. 2010; 16: 2496–503. 9. Pulimood AB, Amarapurkar DN, Ghoshal U et al. Differentiation of Crohn’s disease from intestinal tuberculosis in India in 2010. World J. Gastroenterol. 2011; 17: 433–43. 10. Singh O, Gupta S, Moses S, Jain DK. Spontaneous tubercular enterocutaneous fistula developing in the scar of a surgery done 14 years earlier. Saudi J. Gastroenterol. 2009; 15: 261–3.

Angelika F. Na,* MBBS, BMedSci Shaun Brown,† MBBS, FRCPA Raaj Chandra,* MBBS, BMedSci, FRACS *Department of General Surgery, The Royal Melbourne Hospital, Melbourne, Victoria, Australia and †Department of Pathology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia doi: 10.1111/ans.13016

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Appendiceal tuberculosis.

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