A 33-year-old Haitian immigrant with 7 months of abdominal pain and progressive distension

Abstract

We report a case of a 33-year-old previously healthy Haitian immigrant with a 7-month history of abdominal pain, fever and ascites. He had a history of positive tuberculin skin test but never underwent treatment for latent tuberculosis (TB) infection. Initial examination showed abdominal distension. Abdominal CT scan showed mild ascites, abnormal soft tissue in the greater omentum and small bowel mesentery, retroperitoneal adenopathy, peritoneal thickening and dilated loops of small bowel. Paracentesis and thoracentesis were initially non-diagnostic. HIV testing was negative. The differential diagnosis included lymphoma and TB peritonitis. The omental mass was biopsied under ultrasound guidance, and histopathology revealed non-necrotising granulomas. Sputum cultures and omental biopsy cultures subsequently grew Mycobacterium tuberculosis, and a diagnosis was made of pulmonary TB with TB peritonitis. The patient responded well to the initiation of anti-TB treatment.

Background

This case highlights the challenges in diagnosing tuberculous (TB) peritonitis. TB peritonitis should be considered in the differential diagnosis for a patient with fever, abdominal pain and ascites particularly if coming from endemic areas. Since the ascitic fluid culture is usually negative for mycobacterial growth, other diagnostic tools, such as adenosine deaminase (ADA) and PCR-based assays should be used to help make the diagnosis. Ultimately, tissue biopsy may be needed to confirm the diagnosis of TB peritonitis. A high index of suspicion is necessary as delays in diagnosis can result in increased mortality. Finally, strong consideration for treatment of latent TB infection (LTBI) in foreign-born individuals could have averted the development of this clinical presentation.

Case presentation

A 33-year-old Haitian immigrant presented with a 7-month history of abdominal pain, intermittent fever, weight loss and drenching night sweats. One month prior to admission, he noted increased abdominal girth. Two weeks prior to admission, he developed a non-productive cough with associated shortness of breath and chest discomfort. He presented to an outside hospital, where he underwent extensive testing including paracentesis, which showed negative acid-fast bacilli (AFB) smear. Cytology examination was negative for malignancy. The patient left to seek a second opinion at our hospital.

His medical history was notable for a positive tuberculin skin test (TST) in 2005, for which he did not receive treatment. He received the BCG vaccine as a child in Haiti; he immigrated to the USA in 2004. There were no known TB contacts in Haiti or in the USA. He worked at a supermarket. He denied any alcohol or illicit drug use.

On examination he appeared cachectic and chronically ill. Temperature was 101.4°F, blood pressure 107/81 mm Hg, heart rate 115 bpm, oxygen saturation 100% on room air. There was no lymphadenopathy. There were bronchial breath sounds at the right lung apex and dullness at the lung bases. His abdomen was distended, non-tender, and with shifting dullness. Hepatomegaly was noted. Trace pedal oedema was present. There was left epididymal thickening.

Laboratory studies showed no leukocytosis. Albumin was 2.9 g/dL and other liver function tests were within normal limits. HIV antibody test was negative.

Chest X-ray revealed moderate-sized bilateral pleural effusions and right apical opacity. Chest CT showed bilateral pleural effusions. Abdominal CT showed a large amount of soft tissue in the greater omentum and along the right paracolic gutter and in the small bowel mesentery; there was mild ascites, mild retroperitoneal lymphadenopathy and peritoneal thickening; there were multiple dilated loops of small bowel (figure 1).

Figure 1.

CT of the abdomen and pelvis with contrast revealed large amount of soft tissue in the greater omentum and along the right paracolic gutter and in the small bowel mesentery. Also seen are mild ascites, mild retroperitoneal lymphadenopathy and peritoneal thickening, as well as multiple dilated loops of small bowel. Arrows point to abnormal omental mass in the paracolic gutter.

Investigations

The patient was placed in airborne isolation due to the concern for tuberculosis (TB). Blood cultures were negative for routine bacteria and AFB. Additional studies were performed. Thoracentesis revealed an exudate. The pleural fluid ADA was 63.1 U/L. AFB stain of the pleural fluid was negative. Direct probe for Mycobacterium tuberculosis complex by GeneXpert MTB/RIF PCR was negative. Cytology was negative for malignancy.

Urine smear was negative for AFB. Sputum was AFB smear negative on two specimens as was GeneXpert MTB/RIF PCR assay.

Paracentesis results from the outside hospital were reviewed. Ascitic fluid showed 1097 cells/mm³ (predominantly lymphocytes). The calculated serum albumin-ascitic fluid gradient (SAAG) was 0.5 g/dL. The peritoneal fluid ADA was 26.8 U/L. AFB smear was negative. GeneXpert MTB/RIF PCR testing was not available.

Quantiferon-TB Gold was >10 IU/mL. Flow cytometry of peripheral blood showed mature polyclonal B cells and normal lymphoid immunophenotype with no phenotypically unique cells suggestive of T-cell lymphoproliferative disorder.

Given the non-diagnostic workup to this point, an ultrasound-guided percutaneous core biopsy of the right upper quadrant omental mass was pursued. The pathology showed non-necrotising granulomas (figure 2), consistent with mycobacterial infection. There was no evidence of malignancy. The omental mass biopsy was AFB negative and the methenamine silver stain was negative for fungal organisms. There was no growth on routine bacterial cultures. GeneXpert MTB/RIF PCR was not performed on the biopsy specimen.

Figure 2.

Histopathology of omental mass biopsy showing fibroadipose tissue with non-necrotising granulomas, chronic inflammation and fat necrosis.

After 2 weeks, the sputum specimens grew 1+M. tuberculosis; susceptibility testing showed sensitivity to all first-line drugs. The omental biopsy specimen grew M. tuberculosis after 4 weeks. The peritoneal fluid culture from the outside hospital was negative for mycobacterial growth.

Differential diagnosis

TB peritonitis, lymphoma, gastrointestinal malignancy, cirrhosis, sarcoidosis, pancreatitis, peritoneal cacinomatosis and congestive heart failure.

Treatment

After the biopsy, the patient was discharged from the hospital and was seen in the outpatient clinic 1 week later. Although cultures were negative to date, with the available biopsy results, the patient was initiated on treatment for likely TB peritonitis. He was started on isoniazid (INH), rifampin, pyrazinamide, ethambutol and vitamin B₆.

Outcome and follow-up

Two months after starting four-drug TB treatment, the patient reported substantial improvement in his symptoms, with improved appetite and resolved fevers. Abdominal and pulmonary examinations were normal. The patient has completed 2 months of four-drug therapy and will complete an additional 4 months of the INH/rifampin.

Global health problem list

• What is the typical presentation of TB peritonitis?

• What current diagnostic modalities are available and validated for diagnosis of TB peritonitis? Is tissue biopsy necessary?

• How should providers approach recent immigrants with latent TB arriving from high TB incidence regions of the world?

Discussion

Extrapulmonary TB manifesting in the abdomen can present with involvement of peritoneum, lymph nodes or enteritis, with TB peritonitis being the most common. TB peritonitis is estimated to represent 0.1–0.7% of all TB cases and is more commonly seen in high TB incidence areas. The entity is more common in patients with underlying alcoholic liver disease, cirrhosis and patients on chronic ambulatory peritoneal dialysis for end-stage renal disease. TB peritonitis results from haematogenous spread from a primary pulmonary infection or from reactivation of latent TB in the peritoneum. The diagnosis can be difficult since the most common findings in TB peritonitis are non-specific: abdominal pain, ascites and fever. The onset is insidious with reported 1–6 months of symptoms prior to diagnosis. Concomitant active pulmonary TB is unusual although abnormal chest findings including pleural effusions are occasionally seen.¹ The most common clinical finding is ascites (71%) but can be underestimated without imaging. Given the challenges in making the correct diagnosis, delays are common, and can result in higher mortality rates.²

Routine laboratory findings are non-specific, with most cases demonstrating anaemia and elevation of serum inflammatory markers.³ Other suggestive studies include exudative ascitic fluid and a low SAAG (<11 g/dL), as seen in our patient. Radiographic findings are generally suggestive although non-specific: ultrasound generally shows ascites. CT scan often shows ascites, peritoneal, and omental and mesenteric thickening. When performed, laparoscopic examination shows thickened hyperaemic peritoneum with military or caseous nodules.

Microbiological testing of ascitic fluid is typically of low-diagnostic yield. Acid-fast staining of peritoneal fluid is unreliable, with sensitivity of 0–6% for diagnosis of TB peritonitis.⁴ Mycobacterial culture of the ascitic fluid, too, is of low yield, with a sensitivity of only 34%.¹ Moreover, cultures can take up to 6 weeks to yield growth, delaying the time to diagnosis. In our patient, culture of ascites was non-diagnostic.

ADA is a non-invasive serum test and a useful diagnostic marker for extrapulmonary TB infection. ADA is an enzyme released by lymphocytes during the cellular immune response, and is thus elevated in the presence of infection, rheumatological disease and lymphoproliferative disorders. ADA is increased in meningeal, pleural, pericardial, synovial and peritoneal fluid when these are infected with TB, with different ADA thresholds set for each type of effusion. The utility of ADA in the diagnosis of abdominal TB is controversial, and the threshold of ADA for diagnosis of TB peritonitis is unknown. A case series by Voigt et al⁵ showed a mean ADA level in ascitic fluid of 99.8 U/L in patients with TB peritonitis, and a sensitivity of 95% and specificity of 98% when using 32 U/L as a cut-off. An independent study also found that when 35 U/L is used as the cut-off, the sensitivity and specificity for diagnosis of TB peritonitis is 100% and 92%, respectively.⁶ The ADA may be affected by underlying liver cirrhosis, and caution should be used when interpreting ADA levels in this clinical context.⁷ In our patient without underlying liver disease, the ascitic fluid ADA was below these cut-offs.

Real-time PCR-based assays, such as GeneXpert MTB/RIF, have been validated for the diagnosis of pulmonary TB, and can be particularly useful in so-called paucibacillary cases of TB, which are smear negative but ultimately culture positive. GeneXpert MTB/RIF has a sensitivity of 67% for smear-negative, culture-positive pulmonary TB.⁸ The assay may also aid in the diagnosis extrapulmonary TB; a recent study tested synovial, peritoneal, pericardial, and pleural fluid, and found a pooled sensitivity of 64% for smear-negative, culture-positive cases when these various fluids were tested.⁹ However, there are currently no large-scale studies examining the use of this assay in diagnosing TB peritonitis, and further studies are needed to evaluate the utility of PCR-based assays in this context. While the WHO endorses use of GeneXpert MTB/RIF PCR for extrapulmonary specimens, the USA has not yet followed suit.

When serum and ascitic fluid studies are non-diagnostic, as in this case, radiological imaging combined with tissue biopsy is indicated. The most common CT scan findings in TB peritonitis are ascites, peritoneal thickening, omental mass, mesenteric involvement and pleural effusions³ as seen in our patient. Since these findings are not specific to TB peritonitis, and may be seen in other diseases such as peritoneal carcinomatosis, tissue biopsy should be obtained. Biopsy shows caseating or non-necrotising granulomas and is considered the gold standard for diagnosis. While laparoscopy or open laparotomy with peritoneal biopsy has high sensitivity for diagnosing TB peritonitis (85–100%), image guided percutaneous biopsy of peritoneal lesions is minimally invasive and, combined with histopathology, yields a diagnosis in approximately 90% of cases.^{3 4}

On arrival to the USA, this patient was known to have LTBI. He received the Mantoux TST prior to arrival in the USA, and was told he had a positive result (he could not recall the size). In recent immigrants, such as this patient, induration greater than 10 mm is considered a positive result. Although prior BCG vaccination can sometimes leads to a false-positive TST reaction, the effect of BCG vaccination generally wanes over the time, and a positive TST result is more likely to be due to true TB infection than to BCG reactivity.¹⁰ Interferon-γ release assays (IGRA) such as the Quantiferon-TB Gold test are preferred to TST for patients who have received the BCG vaccine, since IGRA is not susceptible to false-positive results due to prior vaccination. However, IGRA is expensive and is currently not widely available in the developing world.

Our patient presented with active TB 9 years after immigrating to the USA from Haiti, where the incidence of TB is 214/100 000 individuals.¹¹ Although he was known to have LTBI, he was not offered treatment. Immigrants who arrive in the USA from TB endemic regions, such as Haiti, are at high risk for active TB during the first several years after they arrive in the USA.¹² For those who arrive in the USA and later develop active TB, only one-third report having received postarrival testing for latent TB. According to the US Centers for Disease Control (CDC), in 2012, 63.1% of active TB cases occurred in foreign-born individuals.¹³ Since 1967, the CDC has recommended treatment for all individuals with latent TB detected by TST and more recently by IGRA.¹⁴ In contrast, the UK's National Institute for Health and Care Excellence (NICE) recommends treating persons with latent TB if they are younger than 35, co-infected with HIV, or a healthcare worker.¹⁵

Despite the CDC guidelines only 68% of immigrants who are identified overseas as having active or latent TB complete appropriate follow-up once in the USA.¹⁶ Of those who were diagnosed with latent TB after arrival, only half complete appropriate therapy.¹⁷ Our patient, then, is one of many where there was a lost opportunity for treatment. Future initiatives should include expansion of efforts to offer and complete treatment for those at highest risk for TB reactivation.

Patient's perspective.

• At the patient's 2-month follow-up visit, he reflected on his experience and said: “Sometimes I was scared. I did not know what was going on. I knew that, with faith in God, the doctors would reveal the diagnosis. God's gift is to give the doctors knowledge. I thought TB could only be in my lungs. I did not know TB could be in the belly!”

Learning points.

• Tuberculous (TB) peritonitis should be considered in a patient with indolent presentation of fever, abdominal pain and ascites especially if coming from a TB-endemic country, as timely diagnosis is important for prognosis.

• Adenosine deaminase has a high sensitivity and specificity for distinguishing TB peritonitis from other causes of ascites.

• PCR-based assays currently do not have a definitive role in the diagnosis of extrapulmonary TB.

• Image-guided peritoneal biopsy is of high yield for diagnosing TB peritonitis.

• Providers should be aware of identifying patients at risk for latent TB infection (LTBI), such as individuals coming from countries that are endemic for TB, and ensure compliance with local guidelines for treatment of LTBI.