Favourable outcome in a child with presumed tubercular pancarditis treated with empirical antitubercular therapy

Abstract

Cardiac tuberculosis (TB) as an extrapulmonary manifestation of TB is rare. Pericarditis is a common manifestation while myocarditis and endocarditis are less common. Tubercular pancarditis is extremely rare. Endomyocardial involvement of TB is generally clinically silent and present as sudden death due to arrhythmias. It is recommended that empirical antitubercular therapy (ATT) on the basis of clinical suspicion should be avoided in countries where TB is highly prevalent. However, delaying ATT in endomyocardial TB and extensive investigations for demonstration or culture of acid-fast bacilli (AFB) may be associated with morbidity and may lead to catastrophic consequences, especially in a sick child. We present a child with TB pancarditis who presented with congestive cardiac failure and empirical ATT was started after extensive efforts to demonstrate AFB failed and the outcome was good.

Background

Tuberculosis (TB) is a serious public health concern in low-to-middle-income countries (LMICs). Extrapulmonary TB accounts for 15%–20% of mycobacterium infections in children.¹ Cardiac involvement described in autopsy findings is seen in less than 0.5% of adult TB cases. Tubercular pericarditis is seen frequently while tubercular myocarditis (0.3%) and endocardial involvement (0.1%) are rare.^2–4 Tubercular pancarditis is described very rarely in isolated case reports.⁵

The recommendation in countries with a high prevalence of TB is not to start empirical antitubercular therapy (ATT) on the basis of clinical suspicion and all efforts should be exercised for demonstration of acid-fast bacilli (AFB).¹ In childhood extrapulmonary TB, which is paucibacillary, it may not always be possible to follow these recommendations. Particularly in cardiac TB, especially with endomyocardial involvement, delaying the diagnosis may lead to catastrophic consequences as the majority of cardiac TB are diagnosed either on autopsy or they present with sudden death.^{4 6} We present a female child with TB pancarditis who presented with congestive cardiac failure (CCF) and empirical ATT was started after extensive efforts to demonstrate AFB failed and she had a good outcome.

Case presentation

An 11-year-old female child was admitted with low-grade fever, progressive breathlessness on exertion and swelling of both lower limbs and face of 2-month duration. There was a history of associated unquantified weight loss and loss of appetite. There was no history of cough, palpitation, jaundice, blood loss, blood transfusions, rashes, joint or bone pain, joint swelling, decreased urine output and similar problems in the past. She was adequately immunised. She belonged to middle socioeconomic strata with no history of contact with a case of TB.

Examination revealed tachycardia (heart rate=108/min), with tachypnoea (respiratory rate=28/min) and normal oxygen saturation. Her jugular venous pressure (JVP) was raised and she had bilateral pitting pedal oedema. BCG vaccine scar was seen in the left deltoid region. There was no pallor, cyanosis, clubbing, icterus or lymphadenopathy. Breath sounds were decreased in right infrascapular and infraxillary regions. Cardiovascular examination showed apex beat in left fifth intercostal space in the midclavicular line and there was no heave. Heart sounds were muffled, S3 was appreciable, P2 was normal in character and there was no murmur. The liver was enlarged 4 cm below the right subcostal margin with a span of 14 cm. There was no splenomegaly or signs of free fluid in the abdomen. Rest of the systemic examination was normal.

In view of tachycardia, tachypnoea and raised JVP with pitting oedema with decreased breath sounds, a clinical possibility of cardiorespiratory illness was thought of and the patient was investigated.

Investigations

The baseline complete blood count (CBC) and biochemical parameters of the child were as depicted in table 1. A chest X-ray (CXR) showed pleural effusion on right side (figure 1). Ultrasonography of the chest was suggestive of bilateral pleural effusion (right >left). A diagnostic pleural tap was done and pleural fluid was found to be exudative as per Light’s criteria.⁷ ECG showed normal sinus rhythm with no QT prolongation. Echocardiography revealed a 29.5×22.6 mm intracardiac mass on the lateral side of the right atrium, myocardium was thickened with speckled calcification, mild to moderate biventricular dysfunction with left ventricular ejection fraction of 45% and features of constrictive pericarditis (thickness 6 mm)(figure 2, video 1). In view of cardiac mass and clinical suspicion of TB, a detailed workup was done (table 1). In view of non-characteristic CXR findings of TB with positive tuberculin skin test (TST), a CT scan of the chest was done which was suggestive of multiple mediastinal lymphadenopathies (largest 12 mm size) with multiple pericardial and myocardial deposits with small consolidation of the left upper lobe of the lung (figure 3). Contrast-enhanced MRI of the heart was also suggestive of discrete pericardial and myocardial deposits. Contact screening was offered for parents and siblings and no evidence of TB was revealed.

Table 1.

Investigations of the index child

Test	Results	Normal range
Complete blood count
Haemoglobin (g/L)	112	117–157
Total leucocyte count (TLC) (×109/L)	6.9	4–11
Differential leucocyte count	Neutrophils: 60%; lymphocytes: 30%; monocytes: 8%; eosinophils: 2%
Platelet count (×109/L)	209	150–450
Peripheral blood film	Normocytic normochromic, no immature cells/blasts
Biochemistry
Blood urea (mmol/L)	6.0	1.7–8.5
Serum creatinine (µmol/L)	30.4	25–79
Sodium (mmol/L)	139	133–144
Potassium (mmol/L)	4.5	3.4–5.3
Bilirubin (µmol/L)	11.8	3.4–22.2
Aspartate transaminase (U/L)	35	0–45
Alanine transferase (U/L)	30	0–50
Lactate dehydrogenase (LDH) (U/L)	232	240–480
Total protein (g/L)	78	63–82
Uric acid (mmol/L)	0.23	0.05–0.41
Pleural fluid analysis
Appearance	Straw colour
TLC (×109/L)	2.9 (predominantly lymphocytes)
Glucose (mmol/L)	5
Protein (g/L)	40
Albumin (g/L)	16
LDH	186
Pleural fluid LDH: serum LDH	0.8	>0.6—exudative
Pleural fluid protein: serum protein	0.52	>0.5—exudative
Malignant cells	Negative
AFB stain	Negative
Adenosine deaminase (U/L)	15	>40
Investigations for aetiological diagnosis
Tuberculin skin test	15 mm	>10 mm
Sputum for AFB	Negative on 03 occasions
Cartridge based nucleic acid amplification test for TB in sputum and pleural fluid	Negative
HIV ELISA	Non-reactor
Antinuclear antibody ELISA (U/mL)	5.3	<10.0
Antistreptolysin O titre	Negative
Urine examination	Protein—nil; RBC—nil; casts—nil
Miscellaneous
C-reactive protein (mg/L)	<50	10–100
Ultrasonography abdomen	Bilateral pleural effusion (right >left); mesenteric lymphadenopathy (largest 14 mm) and no ascites
Blood/pleural fluid/sputum culture	Sterile

AFB, acid-fast bacilli; TB, tuberculosis.

Figure 1.

A chest X-ray (posteroanterior view) showing the right-sided pleural effusion.

Figure 2.

Apical four-chamber view on echocardiography showing echogenic mass measuring 29 mm×22 mm along the lateral wall of the right atrium (bold white arrow).

Video 1.

Download video file ^{(584.2KB, mp4)}

DOI: 10.1136/bcr-2020-235125.video01

Figure 3.

CT scan of the chest showing pericardial thickening (single thin arrow), right atrium endocardial tuberculoma (double arrow) and multiple pericardial and myocardial deposits (bold white arrow).

Differential diagnosis

After clinical examination and baseline investigations, a differential diagnosis of disseminated TB, acute rheumatic fever, non-Hodgkin lymphoma, leukaemia and connective tissue disorder was contemplated. With consolidation in lung, exudative pleural effusion, generalised mediastinal and retroperitoneal lymphadenopathy, with a positive TST, a diagnosis of TB despite the inability to demonstrate AFB and negative cartridge-based nucleic acid amplification test was considered. Normal CBC with no features of tumour lysis syndrome, peripheral blood film showing no atypical cells, pleural fluid not showing malignant cells, negative ASO titre, no evidence of valvulitis on echocardiography and negative ANA helped in the exclusion of the diagnosis other than TB. The consultation of the interventional radiologist was sought for a diagnostic sampling of mediastinal and/or retroperitoneal lymph nodes. However, in view of the small size of lymph nodes, it could not be done. A biopsy of the cardiac mass and bronchoalveolar lavage was considered hazardous especially in view of associated CCF and was not attempted. In view of a strong clinical and radiological suspicion, positive TST in an endemic zone after excluding other alternative aetiologies, a diagnosis of ‘possible TB’ was made.

Treatment

Initially, the child was managed with oral frusemide (2 mg/kg/day) and enalapril (0.1 mg/kg/day). After the diagnosis of ‘possible TB’, a therapeutic trial of ATT was started as per Revised National Tuberculosis Control Programme guidelines with 2 months of intensive phase with four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) along with oral prednisolone at 2 mg/kg/day for 6 weeks.⁸ After an intensive phase of 2 months, the child was afebrile, gained 3 kg of weight, appetite and general condition improved. CXR revealed complete resolution of pleural effusion. Repeat echocardiography was suggestive of decreasing size of right atrium mass (9 mm diameter) and decreasing pericardial thickness (4 mm) with improving ejection fraction (55%). In view of clinical and echocardiographic improvement, the continuation phase of ATT with three drugs (isoniazid, rifampicin and ethambutol) was given for 4 months. Anticardiac failure medications were stopped after 4 months.

Outcome and follow-up

Repeat echocardiography done after the completion of total 6 months of ATT showed a complete resolution of right atrium mass with normal biventricular functions with pericardial thickening of 3 mm. She was asymptomatic and had gained 8 kg of weight since the start of ATT. As pericardial thickening is persistent, she is planned to be followed up on 3 monthly basis for features of constrictive pericarditis.

Discussion

TB remains a considerable public health problem in LMIC like ours.¹ Cardiac involvement is rare in TB. Possible mechanisms for cardiac involvement in TB includes the role of proinflammatory cytokines, monocyte macrophage immune activation and autoantibodies directed to the mycobacterium HSP65 protein.⁹ The heart and pericardium may be infected by mycobacterium via haematogenous spread occurring during primary TB infection, and also by direct peribronchial or lymphatic dissemination. The most common form of cardiac involvement by TB is pericarditis with the long-term development of calcific constrictive pericarditis. Other forms of cardiac involvement are quite rare and include myocarditis and endocarditis. Endocardial involvement may be in the form of valvulitis or it may involve the endothelial surface of cardiac chambers as cardiac tumours. TB myocarditis is clinically silent and generally present as sudden death following a fatal arrhythmia and antemortem diagnosis is extremely rare.^{6 9} The index child had constrictive pericarditis and pericardial deposits, thickened myocardium with calcification and large intra-atrium tuberculoma suggesting the involvement of all three layers of the heart.

The incidence of cardiac TB is higher in immunocompromised or HIV-infected patients. HIV infection increases the risk of cardiac TB by 1.5-fold to 2-fold. The reasons cited are immune activation and opportunistic infection.⁹ The index child was immunocompetent.

The proposed criteria on the diagnosis of TB myocarditis include a positive AFB or positive culture or identification of TB DNA extracts from myocardial samples.⁶ Surgery or a percutaneous vascular catheter-guided biopsy have been tried for sampling. Indications of surgery in cardiac TB are- the uncertain diagnosis, refractory arrhythmias, thromboembolism, haemodynamically significant obstruction and inadequate response to medical treatment.¹⁰ In the absence of a disseminated disease, when the sample for demonstrating AFB from other tissues is unavailable, sampling cardiac tissue especially if associated with CCF or arrhythmias may be associated with morbidity.⁶ MRI chest, CT chest, TST and echocardiography may provide supporting evidence for the diagnosis of cardiac TB. It is suggested that the presence of pericarditis along with an infiltrating mass lesion on cardiac MRI in an appropriate clinical scenario is a good pointer to cardiac TB rather than a malignant tumour and may help in avoiding invasive and morbid investigations.¹¹

In the index child, there was a clinical suspicion of TB, however, AFB could not be isolated. Any further invasive tests to biopsy the mass lesion were considered hazardous especially in the presence of CCF. Empirical ATT was therefore offered and there was a complete resolution of endomyocardial mass. A similar case in a 15-month-old child with suspected myocardial TB responding to empirical ATT has been described.¹² Apart from ATT, the child received 6 weeks of oral steroids as adjuvant therapy. The steroids were indicated in view of the pericarditis as evidenced by the presence of pericardial thickening in index child. As per European Society of Cardiology 2015 guidelines, in endemic zone, steroids are recommended for constrictive pericarditis.¹³ A high index of suspicion for the start of ATT is therefore required especially with myocardial involvement because the early start of ATT in cardiac TB is associated with the resolution of complications while the delay is associated with adverse outcome.^{12 14 15}

Mother’s perspective.

My daughter was sick for 2 months. But since her father was away, I did not take medical consultation. But once she started complaining of progressive breathlessness on walking, I brought her to medical attention. After many investigations, I was told that the suspicion of tuberculosis is high, however it could not be proven. It was also conveyed to me that in view of the poor condition of the heart of my daughter, few of the invasive tests may not be advisable; therefore, an empirical therapy for TB was offered. My child was kept on regular follow-up. Her general condition and symptoms slowly started improving. After 2 months, I was told that the response to therapy was very favourable and full 6 months of therapy will be given. After 6 months, my daughter is absolutely fine. She has gained 8 kg weight. We have been advised to follow-up every 3 months.

Learning points.

• Cardiac tuberculosis (TB) is a rare form of extrapulmonary TB in children.

• TB pancarditis as seen in index child is extremely rare.

• Demonstration of acid-fast bacilli or a positive mycobacterium culture may be difficult and associated with morbidity in endomyocardial TB.

• Empirical antitubercular therapy, after reasonable efforts fail to demonstrate mycobacterium, maybe lifesaving in cardiac TB especially with the involvement of myocardium.