This is a common cause of chronic pericardial

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1 clinical Study Tuberculous Pericardial Effusion GS SAINANI, RAJESH G SAINANI Abstract Tuberculous pericardial effusion is common in Afro-Asian countries. Since, the introduction of HIV infection, the incidence of tuberculous pericardial effusion has increased not only in Afro-Asian countries but also the world over. It presents with the usual features of tuberculous infection (low grade fever, loss of appetite, loss of weight) along with features of pericardial effusion (dyspnea, cough and enlarged heart). The salient features of pericardial effusion are low volume pulse or even pulsus paradoxus, raised jugular venous pressure Kussmaul s sign, congestive hepatomegaly, ascites and edema over legs. In massive pericardial effusion, patient may go into cardiac tamponade when patient is breathless, restless with poor volume pulse (typical paradoxus), engorged neck veins, sinus tachycardia, fall in blood pressure. Urgent pericardial paracentesis is warranted to reverse the hemodynamic changes with improvement in symptoms and signs. Laboratory tests reveal raised absolute lymphocyte count, raised ESR, cardiomegaly on X-ray chest, low voltage and sinus tachycardia on ECG, Echo-free space seen between two pericardial layers on 2D-echo with heart floating in pericardial sac. Diagnostic pericardial paracentesis shows that pericardial fluid is lymphocytic exudate, with elevated ADA and IFN-g levels. Tubercle bacilli may be isolated on culture, guinea pig inoculation and nowadays by PCR technique. For management of tuberculous pericardial effusion, antituberculous treatment with four standard drugs is started. Pericardial paracentesis with needle or even open drainage is useful in relieving symptoms and rapid recovery. Adjunctive corticosteroids are useful for rapid recovery and for prevention of development of constrictive pericarditis. Keywords: Nasopharynx, foreign bodies, sewing needle This is a common cause of chronic pericardial effusion particularly in Afro-Asian countries. It has become more common since occurrence of HIV infection. It is relatively less common in welldeveloped countries. (USA, UK, Canada, Europe). Infection is either blood-borne or spread from neighboring structures like lymph nodes, lungs and bronchi. The patient presents with general features of tuberculosis such as low-grade fever, loss of appetite, loss of weight and fatigability, cough along with features of pericardial effusion. 1 Clinical features of pericardial effusion Symptoms vary according to the amount of pericardial fluid which may vary from 150 ml to 1,000 ml. Dyspnea is very common symptom and its severity will vary according to the quantity of fluid. The dyspnea is due to compression of the adjacent lungs and bronchi. Patient feels worse in lying down position and feels better in sitting and leaning forward as that posture reduces the compression of lungs and bronchi. Cough is another Dept. of Medicine, Jaslok Hospital and Research Centre, Mumbai Address for correspondence Dr GS Sainani 201, Buena Vista Gen. Jagannath Bhosle Road, Mumbai drsainani@vsnl.com common symptom and is attributable to compression of bronchi. Rarely, one may encounter hoarseness of voice or difficulty in swallowing due to pressure on recurrent laryngeal nerve or esophagus (seen in massive pericardial effusion). On physical examination, patient looks, thin, emaciated, febrile, dyspneic and usually in propped up position. Pulse is small in volume or may have typical pulsus paradoxus (poor volume in inspiration and slightly better volume in expiration). Blood pressure is on lower side. There may be distension of neck veins with presence of Kussmaul s sign (Jugular venous pressure rising during inspiration and lower during expiration). There may be tender hepatomegaly and in some chronic cases there is free fluid in abdomen (ascites). There is invariably pitting edema over both legs. 2 Precordial examination may show slight bulging (fullness of intercostal spaces), cardiac impulse and other pulsations usually not visible. Apex beat may be just palpable. On percussion heart borders are enlarged. On left side, one may get dull percussion note beyond apex beat; on right side, one gets dull percussion note on right side of the sternum particularly in 5th intercostal space (Rotch s sign). One may be able to demonstrate shifting dullness in left second space which is dull in recumbent position and becomes less dull in sitting position due to shifting of fluid down. In some cases Indian Journal of Clinical Practice, Vol. 22, No. 8, January

2 clinical study of massive pericardial effusion, one can demonstrate Ewart s sign (Dull note along with bronchial breathing and egophony over left infrascapular region due to compression of the lower lobe of left lung by pericardial fluid). On auscultation, heart sounds are distant. Rarely, one may hear a pericardial rub. 2 In massive pericardial effusion, patient may drift into cardiac tamponade, which should be recognized and managed, on emergent basis. The clinical features of tamponade are due to impaired diastolic filling leading to low cardiac output due to increased intrapericardial pressure. It should be stressed that presentation of cardiac tamponade is due to rapidity with which the fluid collects rather than total quantity of fluid. If fluid starts collecting gradually over a long period, the heart adopts and cardiac tamponade does not develop. But if fluid collects rapidly, ventricular filling is impaired which leads to increase in diastolic pressure resulting in rise in atrial pressure, fall in stroke volume and cardiac output. That is reflected in compensatory sinus tachycardia and fall in systolic blood pressure. Increase in atrial pressures leads to rise in jugular venous pressure. Patient gets severe breathlessness in recumbent position (orthopnea) and he finds some comfort in sitting position and leaning forward. He may develop cyanosis. Heart sounds are distant and one may hear III heart sound. Pericardial paracentesis (preferably under echocardiographic guidance) is urgently warranted to reverse the hemodynamic alterations. 1,2 Investigations Blood: Total leukocyte count is usually normal with lymphocyte predominance. Absoute lymphocyte count is raised, erythrocyte sedimentation rate (ESR) is raised. X-ray: Chest shows enlarged cardiac shadow. In massive effusion, heart looks funnel shaped. The contours due to chambers and blood vessels are lost. One can assess the thickness of pericardium by injecting air in pericardial cavity after aspirating some fluid (which results in hydropneumopericardium). MRI: Hayashi et al 3 reported a patient in when gadolinium enhanced magnetic resonance imaging (MRI) provided useful information. The incidence of tuberculous pericarditis has decreased but early diagnosis and treatment are critical because constrictive pericarditis is a serious complication which has a poor prognosis. 4 MRI has recently been used to evaluate suspected pericardial heart disease 5 and few reports on MRI findings in tuberculous pericarditis are available. 6,7 ECG: There is low voltage and sinus tachycardia, T waves are usually inverted. Echocardiography: This is most useful and confirmatory as one sees echo-free space between two pericardial layers. In massive pericardial effusions, one would see heart floating in pericardial sac. 2 Cardiac catheterization: Before the advent of 2D-echo, cardiac catheterization and ventricular angiography used to be done to confirm and evaluate the severity of pericardial effusion. 2 Diagnostitic pericardial paracentesis: Pericardial paracentesis for diagnositic and therapeutic purposes are carried out under echocardiographic scanning. On aspiration, the fluid is straw colored or sometimes blood tinged. The fluid is sent for cytology, biochemistry, Ziehl-Neelson stain and culture for tubercle bacilli. Guinea pig inoculation may confirm tuberculous etiology. The fluid is lymphocytic exudate. (Proteins are increased and there is predominance of lymphocytes). For therapeutic purposes, it is carried out in cardiac tamponade to relieve dyspnea, palpitation. 2 Gibbs et al 8 in their survey of 10 years experience of patients of pericardial effusion (who were managed by percutaneous paracentesis) had 46 patients of pericardial effusion. Amongst these, they documented 12 cases of tuberculous pericarditis, nine were Indo-Asian and three were of Afro-carribean origin. Fever, night sweats and weight loss were common among these patients. Pulsus paradoxus was the most important sign (100%) for the presence of echocardiographic features of tamponade. According to them pericardiocentesis remains an effective measure for immediate relief of symptoms of cardiac tamponade. Reuter et al 9 have stressed on laboratory tests for diagnosing tuberculous pericarditis. Definitive diagnosis of tuberculous pericarditis requires isolation of the tubercle bacillus from pericardial fluid, but isolating the organism is difficult. The authors studied 233 consecutive cases of pericardial effusion who underwent a predetermined diagnostic work-up. This included (i) Clinical examination (ii) pericardial fluid tests: Biochemistry; microbiology, cytology, differential white blood cell (WBC) counts, gamma-interferon (IFN-g), adenosine deaminase (ADA) levels, polymerase chain reaction (PCR) testing for mycobacterium tuberculosis (iii) HIV (iv) sputum smear and culture (v) blood biochemistry and (vi) differential WBC count. 372 Indian Journal of Clinical Practice, Vol. 22, No. 8, January 2012

3 clinical study These results showed that fever, night sweets, weight loss, serum globulin (>40 g/l) and peripheral blood leukocyte count (<10 x 10 9 /l) were independently predictive. Pericardial fluid IFN-g 50 pg/ml concentration, had 92% sensitivity, 100% specificity and a positive predictive value (PPV) of 100% for diagnosis of tuberculous pericarditis. Pericardial fluid ADA 40 U/l had 87% sensitivity and 89% specificity. A diagnositic model including pericardial ADA, lymphocytic/neurtophic ratio, peripheral leukocyte count and HIV status had 96% sensitivity and 97% specificity; substituting pericardial IFN-g for ADA yielded 98% sensitivity and 100% specificity. They concluded that pericardial IFN-g is the most useful diagnostic test. Alternatively they propose a prediction model that incorporates ADA and differential WBC counts Burgess et al 10 have stressed that traditional diagnostic tests for tuberculous pericarditis are insensitive and often require long culture periods. Hence, newer tools such as pericardial ADA and IFN-a were investigated by Burgess et al and they concluded that pericardial fluid levels of ADA and IFN-a are useful in the diagnosis of tuberculous pericarditis. Mathur et al 11 carried out study on 120 cases of serosal effusion (50 pleural, 50 peritoneal and 20 cases of pericardial effusion). ADA was found significantly raised with a mean value of 100 U/l, 92 U/l and 90 U/l in tubercular pleural, peritoneal and pericardial effusion respectively with overall 100% sensitivity and 94.6%, specificity and cut-off value of 40 U/l. Cherian 12 in his review article has suggested the following criteria for diagnosis of tuberculous etiology of pericardial effusion: Culture of Mycobacterium tuberculosis from pericardial fluid or tissue Pericardial tuberculous granuloma with acid-fast bacilli Pericardial tuberculous granuloma + positive tuberculin skin test Tuberculous granuloma in scalene node or peripheral lymph node or pleura with positive tuberculin test. Active tuberculosis elsewhere in the body Mediastinal lymph nodes (matted with central necrosis) on CT chest/abdomen Response to specific antitubular therapy. Mishra et al 13 in their study of 31 tuberculous (20 pleural, 8 ascites and 3 pericardial) and 24 nontuberculous (10 transudative ascites, 8 pyopericardium) effusions evaluated PCR, ADA activity and absolute lymphocyte count (ALC). Their results showed that fluid PCR for M. tuberculosis was positive in 74% of tuberculous effusions, where as it was falsely positive in 13% of the nontuberculous group. The mean fluid ADA and ALC values were significantly higher in tuberculous effusions than in nontuberculous effusions (p < 0.001). The sensitivity and specificity of PCR, ADA and ALC were 74% and 88%, 81% and 75%, and 90% and 83%, respectively in diagnosing tuberculous effusions. They concluded that fluid PCR should not be relied on as a single test; rather, combined analysis with ADA or ALC could be more useful in the diagnosis of tuberculous effusions in children. Diagnosis The diagnosis is confirmed by history of low-grade fever, malaise, loss of appetite, loss of weight, cough, dyspnea and clinical signs of pericardial effusion. X-ray chest, EKG and 2D-echo confirm the diagnosis of pericardial effusion. Examination of pericardial fluid would differentiate the other etiological causes of pericardial effusion. One should rule out viral, rheumatic, purulent and collagen disorders as causes of pericarditis. For confirmation of tuberculous aetiology, one should do culture of M. tuberculosis, do pericardial fluid PCR, estimate ADA and IFN-g levels in pericardial fluid. Raised ESR, elevated absolute lymphocyte count, lymphocytic exudative nature of pericardial fluid, fluid PCR for M. tuberculosis, elevated ADA and IFN-a or g help in confirming the tuberculous etiology of pericardial fluid. Treatment Antituberculous treatment with primary four drugs (rifampicin, isoniazid, pyrizinamide and ethambutol) is given for first two months. Later pyrizinamide is omitted and the remaining three drugs are given. Total 9-12 months of treatment is recommended with periodic follow-up of symptoms and signs of pericardial effusion, ESR, X-ray chest, ECG and 2D-echo till the complete disappearance of fluid and other clinical features. 2 Strang et al 14 in their 10-year follow-up concluded that in the absence of specific contraindication, corticosteroid should be prescribed in addition to antituberculous chemotherapy in the treatment of tuberculous pericardial effusion. The ability of prednisolone to prevent complication of constrictive pericarditis and thus reduce the need for pericardiectomy is important. Standard treatment for pericardial effusion is Indian Journal of Clinical Practice, Vol. 22, No. 8, January

4 clinical study pericardiocentesis which is safe, especially under echo guidance. However, open drainage on admission, in their experience, proved to be more effective and it virtually eliminated the need for repeat pericardiocentesis. According to Wragg and Strang, 15 tuberculous pericarditis is increasing in sub-saharan Africa where tuberculosis is the most common opportunistic infection complicating HIV infection. Adjunctive prednisolone is beneficial in HIV seronegative patients with TB pericardial effusion, reducing the risk of recurrent tamponade, death from pericarditis and constriction. 16 Benefit from similar treatment in HIV seropositive patient is encouraging, particularly where the absence of antiretroviral drugs worsens the prognosis. Adjunctive prednisolone in Hakim s study 17 resulted in significant improvement in clinical condition and faster resolution of physical signs of pericardial effusion. Trautner and Darouiche 18 reported their experience of 10 cases of tuberculous pericarditis. They addressed four specific topics: (1) The importance of tissue for diagnosis (2) The optimal surgical management; (3) The role of corticosteroids and (4) The impact of HIV infection on the management of the disease. They concluded from their experience of 10 cases and review of literature that the optimal management should include an open pericardial window with biopsy both for the diagnosis and to prevent reaccumulation of fluid. Corticosteroids offer benefit in preventing fluid reaccumulation and preventing development of constrictive pericarditis. Patients with HIV seropositive also had an excellent response to open drainage, corticosteroids and antituberculous therapy. They stress that pericardial tissue specimens should be obtained to provide the best chance of definitive diagnosis. Mayosi et al 19 searched MEDLINE (Jan 1966 to May 2005) and the Cochrane Library to review and summarize the literature on the pathogenesis, diagnosis and management of tuberculous pericarditis. A definite diagnosis of tuberculous pericarditis is based on the demonstration of tubercle bacilli in pericardial fluid or on histological section of the pericardium; a probable diagnosis of tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a patient with pericardial effusion, raised ADA levels with lymphocytic pericardial fluid exudate and/or response to anti-koch s treatment with four primary drugs. According to their review, role of adjunctive corticosteroid in preventing progression to constrictive pericarditis or reducing mortality is still not clear. The timing of pericardiectomy is not clear but majority workers recommend a trial of medical therapy and surgery in those who do not respond after six months medical therapy. Reuter et al 20 in their study of 57 patients of tuberculous pericarditis with adjunctive corticosteroids concluded that intrapericardial and oral corticosteroids were welltolerated but did not improve the clinical outcome. In their experience, standard 4-drug treatment for six months was effective even in HIV-positive patients. They could not demonstrate, in their 3-year study, the significant benefits from adjunctive corticosteroids in tuberculous pericarditis. Conclusion Tuberculosis is an important etiological cause of pericardial effusion in Afro-Asian countries. Now with spread of HIV infection, the incidence of tuberculous pericardial effusion has increased not only in Afro- Asian countries but also all over the world. Improved techniques for recovery of M. tuberculosis, the use of PCR technology, ADA levels, pericardial IFN-g, absolute lymphocyte count, detection of mediastinal lymphnodes on CT and more clearly defined observations on 2D-echo have improved the percentage of proper diagnosis. For management, apart from antibuberculous regime, pericardial parocentosis or open drainage and corticosteroids (oral and/or intrapericardial) have improved the morbidity, mortality and reduced the sequalae of constrictive pericarditis. References 1. Fowler NO. Tuberculous pericardiatis. JAMA 1991;266(1): Sainani GS. Pericarditis with effusion. API Text Book of Medicine. Sainani GS, (Ed.), published by Association of Physicians of India Mumbai 2001: Hayashi H, Kawamata K, Machida M, Kumuzaki T. Tuberculous pericarditis: MRI features with contrast enhancement. Br J Radiol 1998;71(846): Desai HN. Tuberculous pericarditis. A review of 100 cases. S Afr Med J 1979;55(22): Stark DD, Higgins CB, Lanzer P, Lipton MJ, Schiller N, Crooks LE, et al. Magnetic resonance imaging of the pericardium: normal and pathological findings. Radiology 1984;150(2): D Silva SA, Nalladaru M, Dalvi BV, Kale PA, Tendolkar AG. MRI as guide to surgical approach in tuberculous pericardial abscess. Case report. Scand J Thorac Cardiovasc Surg 1992;26(3): Clifford CP, Davies GJ, Scott J, Shaunak S, Sarvill J, Schofield JB. Tuberculous pericarditis with rapid progression to Cont d on page Indian Journal of Clinical Practice, Vol. 22, No. 8, January 2012

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