Abstract
Tuberculous pericarditis is uncommon in the Western world, and can prove a diagnostic quandary in that confirmation of the diagnosis and culture of mycobacteria can be difficult. We present a case of tuberculous pericarditis where endobronchial ultrasound-guided transbronchial needle biopsy of a pathological lymph node provided the diagnosis after other methods of investigation had proved futile.
Keywords
Case report
Clinical features and medical history
A 44-year-old gentleman was admitted via primary care, with a two-month history of night sweats. He also complained of myalgia, malaise and intermittent respiratory upset. He had no significant previous medical history and was on no regular medications. He was born in Pakistan, where he had been resident prior to his arrival in the UK, 18 months previously. His family, consisting of his wife and three children, had arrived three months prior to his admission. Two months prior to admission he had been treated in the community for a lower respiratory tract infection after presenting to his general practitioner with fever and productive cough.
Investigation
A chest radiograph demonstrated consolidation of the right lower lobe, though this had resolved on a repeat X-ray, performed after a week of oral amoxicillin and clarithromycin. The patient continued to experience night sweats, however, and routine blood tests revealed iron deficiency anaemia, deranged liver function tests and persistently elevated inflammatory markers.
The patient was therefore admitted to hospital for investigation. Observations demonstrated regular episodes of pyrexia. Examination revealed a persistent tachycardia, 1 cm hepatomegaly, with no lymphadenopathy or splenomegaly. Respiratory and cardiovascular examinations were unremarkable.
He was confirmed to have iron deficiency anaemia and a nonspecific derangement of liver enzymes. The C-reactive protein was raised at 57 mg/L, with an erythrocyte sedimentation rate of 101 mm/hour. A blood film demonstrated a neutrophilia but was otherwise unremarkable, and no malaria parasites were seen. Immunoglobulins were within normal limits with no paraprotein on electrophoresis and antinuclear antibody. Anti neutrophil cytoplasmic autoantibody and rheumatoid factor serology were negative. The patient tested negative for hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus. Cultures of blood, sputum and urine were repeatedly sterile.
An electrocardiogram revealed sinus tachycardia with nonspecific ST-segment changes and a chest radiograph demonstrated clear lung fields with no mediastinal widening.
Transthoracic echocardiography demonstrated a trivial rim of pericardial fluid; however, no effusion or vegetations were seen (Image 1). Around this time, an interferon gamma release assay (QuantiFERON-TB Gold, Cellestis Inc. Cellestis GmbH, Cellestis Europe, Robert Bosch-s/n 7, DE 64293, Darmstadt, Germany) returned as positive, suggesting active or latent infection with Mycobacterium tuberculosis. A computed tomography of chest, abdomen and pelvis was carried out, which demonstrated areas of patchy ground-glass infiltration in the right upper lobe with a number of ill-defined nodules also within the right lung, prominence of the mediastinal and right hilar lymphoid tissue and generalized pericardial thickening (Images 2-4).
Trivial rim of pericardial fluid on transthoracic echocardiography
Pericardial thickening demonstrated on computed tomography imaging of thorax
Mediastinal lymphadenopathy with pathologically enlarged paratracheal node
Nodularity of the right upper lobe
As a result, a diagnosis of pulmonary tuberculosis was strongly suspected. Bronchoscopy, however, revealed only slight nodularity in the right middle lobe and bronchoal-veolar lavage failed to demonstrate mycobacterium. A liver biopsy was carried out which found nonspecific sinusoidal dilation of undetermined aetiology. Neither granulomas nor mycobacteria were observed.
The patient continued to suffer episodes of pyrexia. There was evidence of pericardial restriction manifest as an elevated jugular venous pulsation, tachycardia and hepatomegaly.
Serial echocardiography was performed. The rim of pericardial fluid initially observed, persisted; however, on subsequent echocardiograms the pericardium was noted to be echobright and thickened (Image 5). This was noted to be present both anteriorly and posteriorly, and 0.3 cm in length at its maximum. The right ventricle was found to be mildly hypokinetic; however, there was no right ventricular collapse nor pericardial effusion.
Echobright and thickened pericardium on transthoracic echocardiography
An endobronchial ultrasound was arranged, with the intention to perform biopsy of a hilar lymph node. Again, the bronchoscopy revealed no significant abnormality but biopsy of an enlarged right pretracheal lymph node took place in an uncomplicated fashion. Pathological examination revealed no granulomas or mycobacteria, though the material was sent for culture. This later revealed growth of M. tuberculosis fully sensitive to standard antituberculous regimens.
Management
Following the endobronchial lymph node biopsy, the patient was empirically commenced on antituberculous medications in the form of rifampicin, isoniazid, ethambutamol and pyrazinamide, with adjunctive prednisolone. The swinging pyrexias that were evident previously subsided, and inflammatory markers began to decline.
M. tuberculosis fully sensitive to standard antituberculous therapy was isolated from the pretracheal lymph node sample after 12 days of incubation.
Prognosis and follow-up
The patient remained well over the subsequent two months of outpatient follow-up, and this regimen was reduced to rifampicin and isoniazid.
Tuberculous pericarditis
Tuberculous pericarditis is uncommon in the developed world, accounting for only 4% of non-respiratory tuberculosis in the UK. 1 The incidence is proportional to the incidence of tuberculosis, however, and in sub-Saharan Africa tuberculosis is the commonest cause of pericarditis, and is much commoner. 1 Regardless, M. tuberculosis is often difficult to identify in these cases, and tuberculous pericarditis is associated with significant morbidity and mortality.
Similarly, the aetiology of constrictive pericarditis varies greatly between countries. In the Western world, tuberculosis has decreased in incidence, while mantle chest radiation and intrathoracic operations are now more frequent causes. 2 Clinically, constriction is manifest as right heart failure with muffled heart sounds, an impalpable apical impulse and a pericardial knock on upon examination. Pulsus paridoxus is a reduction in systolic blood pressure of greater than 10 mmHg on inspiration, while Kussmaul's sign is a rise in the jugular venous pulsation on inspiration. These are both classically described in association with constrictive pericarditis but are unreliable for diagnosis. The diagnosis can be confirmed via demonstration of pericardial thickening greater than 2 mm on echocardiography or other imaging modality. It is interesting to note that the syndrome can occur without pericardial thickening being demonstrated and conversely, pericardial thickening can occur without the syndrome of constriction. 2 In the former, it is thought that disease may be confined to the epicardium and thereby difficult to image. As such, cardiac catheterization may be required in these instances to demonstrate the typical findings of constriction, which include increased ventricular interaction.
Tuberculous pericarditis generally results from lymphatic spread from thoracic lymph nodes or haemtogeneous spread from a pulmonary tubercle. 1 Constrictive pericarditis represents the endpoint of an inflammatory process resulting from infiltration of the pericardium by mycobacteria. Initially, a fibrionous exudate develops secondary to cytokine release, mediated by TH1 lymphocytes. There is early granuloma formation as macrophage and lymphocytes are organized around mycobacterium. Later, the exudate is resorbed and granulomas become further organized. Pericardial thickening results from fibrin and collagen production in the inflammatory milieu. Constriction ultimately results as the fibrous pericardium contracts on the myocardium and impairs ventricular filling.
The diagnosis of tuberculous pericarditis can prove difficult, and delay in treatment can be hazardous. 3 Symptoms are generally nonspecific, with fever, night sweats, weight loss and cough the most frequently encountered. 4 The electrocardiogram is usually not normal, with nonspecific ST-segment changes being the most frequently observed abnormality. The most frequent echocardiographic abnormalities are pericardial thickening and the presence of fibrinous pericardial strands, while tamponade is observed infrequently. Pericardial fluid microscopy is insensitive and culture of M. tuberculosis is slow. Caseating granulomas are observed in pericardial fluid in only a minority of patients. Pericardial fluid is invariably exudative, and raised levels of interferon γ and adenosine deaminase are findings more specific to tuberculous pericarditis. Some centres have proposed diagnostic rules based on findings from pericardial fluid; 3 though the problem remains of demonstrating mycobacteria in order to determine their sensitivity to antimicrobials.
In our patient, results of imaging and blood tests guided us towards performing bronchoscopy with bronch-eoalveolar lavage, as well as liver biopsy, in order to obtain material for culture. Early-morning urine samples were also sent, as is routine in investigation of suspected tuberculosis; however, the sensitivity of urine culture has been demonstrated to be as low as 5%. 5 Endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA) allows safe and effective sampling of mediastinal lymph nodes, and is widely used in the staging of bronchial malignancies. 6 Its use in the investigation of mediastinal lymphadenopathy is increasing, as it has several advantages over more invasive approaches such as mediastinoscopy, including a lower rate of major complications and possibility of taking place as a day procedure. 6
Some studies have found the use of EBUS to significantly increase the yield of smear and nucleic acid amplification testing. It is often difficult to obtain culture material in suspected tuberculous mediastinal lymphadenitis, and EBUS-guided biopsy provides a safe and effective method to sample involved lymph nodes. 7
Conclusion and learning points
Even when clinical suspicion is high, tuberculous pericarditis can prove difficult to diagnose and treatment with empirical antituberculous treatment is often undesirable due to adverse effects of antimicrobials;
Conventional methods of obtaining pathology in tuberculous pericarditis cases often have low yield;
EBUS-TBNA provides a safe method of obtaining culture material and can in this case allow for definitive diagnosis of M. tuberculosis.