□ CASE REPORT □

Sudden Caused by Tuberculous with Hemorrhagic

Naoki Hayase 1, Ryota Inokuchi 1,KensukeNakamura1, Ryohei Horie 1, Hajime Sato 2, Toshifumi Asada 1, Naoko Ohashi 1, Miyuki Yamamoto 1, Kanae Nagatomo 1, Rei Ito 1, Masataka Gunshin 1, Takehiro Matsubara 1, Takeshi Ishii 1, Yoichi Kitsuta 1, Susumu Nakajima 1 and Naoki Yahagi 1

Abstract

As still exists in Japan, tuberculous pericarditis is a major health issue. Tuberculous pericardi- tis is difficult to diagnose and leads to poor outcomes when left untreated. We herein report the case of a pa- tient who was admitted to the hospital after undergoing resuscitation for cardiopulmonary arrest. Mycobacte- rium tuberculosis was detected in his hemorrhagic pericardial fluid and tuberculous pericarditis was diag- nosed. The administration of antituberculous medication resulted in marked improvements. A diagnosis of tu- berculous pericarditis, in addition to other causes such as malignant tumors, should therefore be considered in the differential diagnosis for cases presenting with hemorrhagic pericardial effusion, even in those involving sudden cardiac arrest.

Key words: tuberculous, pericarditis, ,

(Intern Med 51: 3197-3201, 2012) (DOI: 10.2169/internalmedicine.51.7958)

We herein report our experience with a patient who was Introduction transported to our emergency and critical care center after undergoing resuscitation for cardiopulmonary arrest. M. tu- Both the prevalence of tuberculosis and the prevalence of berculosis was detected in his hemorrhagic hemopericardial tuberculous pericarditis have been decreasing in Japan. fluid, thus leading to a diagnosis of tuberculous pericarditis. However, tuberculous pericarditis is difficult to diagnose and The administration of antituberculous medication resulted in it also has a mortality rate of 40% (1). Due to the severity a marked improvement. of outcomes in untreated cases and the increasing numbers of immunocompromised patients such as those with human Case Report immunodeficiency virus (HIV) infection, tuberculous re- mains a major health issue in Japan (2, 3). The patient was a 67-year-old man who had not received Tuberculous pericarditis is a form of extrapulmonary tu- medical care at a hospital for more than 40 years and had berculosis that is caused by the direct spread of Mycobacte- been living at a low-cost boarding house for the previous 18 rium tuberculosis from primary lesions in the lungs, bronchi, months. He had been in poor physical condition for four satellite lymph nodes, spinal cord or sternum or by the he- weeks prior to admission. He had gradually developed matogenous spread of M. tuberculosis from distant sites. In edema of the limbs over the previous three weeks and ortho- adults, most cases of tuberculous pericarditis are caused by pnea and loss of appetite over the previous two weeks. He the recurrence of latent lesions, and the location of the pri- had developed abdominal and back pain. At the time of arri- mary lesion is often unclear. val by ambulance, his Glasgow coma scale score was 15/15

１Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital, Japan and ２Department of Health Policy and Tech- nology Assessment, National Institute of Public Health, Japan Received for publication April 13, 2012; Accepted for publication August 19, 2012 Correspondence to Dr. Ryota Inokuchi, [email protected]

3197 Intern Med 51: 3197-3201, 2012 DOI: 10.2169/internalmedicine.51.7958

Table 1. Laboratory Profile

Complete blood count Sodium 130 mEq/L WBC 12,900ȝ/ Potassium 4.4 mEq/L Red Blood Cells 512 × 104 ȝ/ Cloride 98 mEq/L Hb 15.1 g/dL Calcium 8.0 mg/dL Hematocrit 47.4% Phosphorus 4.9 mg/dL Platelet count 21 × 104 ȝ/

Atrial blood gas Chemistry [under a 10-Lreservoir mask] BUN 18.8 mg/dL pH 7.097 Cre 0.90 mg/dL Arterial carbon dioxide tension 73.6 mmHg AST 127 U/L Arterial oxygen tension 57.4 mmHg ALT 90 U/L Bicarbonate ion 21.7 mmol/L LDH 463 U/L Base excess -10.1 mmol/L Amy 37 IU/L Lactate 6.8 mg/dL CK 114 U/L ALP 478 U/L T-Bil 1.4 mg/dL D-Bil 0.6 mg/dL TP 8.3 g/dL Alb 2.3 g/dL CRP 4.63 mg/dL

(eyes: 4; verbal: 5; motor: 6) and he was able to speak and IU/L). In addition, the cytodiagnosis of the pericardial fluid walk. During transportation, he experienced sudden cardio- indicated an absence of abnormal cells. pulmonary arrest (the electrocardiographic monitoring re- To stabilize the patient’s hemodynamic parameters, norad- sults are unknown). Cardiopulmonary resuscitation was initi- renaline was administered until day 3 and dobutamine was ated, and spontaneous circulation returned two minutes later. administered until day 5. Mechanical ventilation was per- On admission (day 0), his blood pressure was 240/130 formed until day 5 (Fig. 2). The patient’s overall status was mmHg, his heart rate was 130 beats/min, his SpO2 was stable; however, large amounts of pericardial and pleural 77%, his temperature was 36.2℃ and his Glasgow coma fluid continued to be drained. The staining results of the scale score was 4/15 (eyes: 2; verbal: 1; motor: 1). The pericardial fluid collected on day 5 were positive for acid- blood test and arterial blood gas analysis findings are shown fast bacilli (Fig. 3). On day 10, the culture results of the in Table 1. The blood tests revealed elevated levels of white pericardial fluid collected on admission were found to be blood cells and C-reactive protein along with liver disorders. positive for M. tuberculosis. The polymerase chain reaction The arterial blood gas analysis revealed marked mixed aci- (PCR) results for M. tuberculosis were also positive, leading dosis and hypoxemia. Therefore, endotracheal intubation to a diagnosis of tuberculous pericarditis. On the same day, was performed. As his hemodynamic parameters were sta- a daily 4-drug combination therapy consisting of isoniazid ble, ultrasonography and contrast-enhanced computed to- (300 mg), rifampicin (450 mg), pyrazinamide (1 g) and mography (CT) were performed; these examinations re- ethambutol (750 mg) was initiated. Predonine (60 mg) and vealed a pericardial effusion, bilateral pleural effusions and vitamin B6 (20 mg) were also administered. pericardial enhancement (Fig. 1A, B). In addition, suspected The volume of the pleural and pericardial fluid drainage miliary tuberculosis was detected on chest CT performed on decreased markedly after the administration of the antituber- admission (Fig. 1C). After 14 days, miliary tuberculosis sub- culous medications. On day 19, echocardiography showed sequently became apparent (Fig. 1D). There were no indica- an ejection fraction of 67%, the absence of asynergy and no tions of aortic dissection, pulmonary thromboembolism, vegetation. Pericardiotomy was not performed. On day 49, esophageal rupture, mediastinitis or pneumothorax. A the patient was discharged and was able to return home on QuantiFERON-TB GOLD In-Tube or tuberculin skin test foot. was not performed. To investigate the cause of the pericardial effusion and to Discussion improve the patient’s respiratory function, the pericardial ef- fusion (200 mL) and pleural effusions (1,000 mL on the Tuberculous pericarditis occurs infrequently; therefore, a right and 1,500 mL on the left) were drained. A transudative definitive diagnosis may be delayed, thus leading to high pleural effusion was detected. The pericardial fluid lympho- rates of mortality and complications such as chronic con- cyte: neutrophil ratio was greater than 1, and the adenosine strictive pericarditis. However, there is no prompt, highly ac- deaminase (ADA) level was 128.6 IU/L (normal range: <30 curate, safe and easy method for diagnosing tuberculous

3198 Intern Med 51: 3197-3201, 2012 DOI: 10.2169/internalmedicine.51.7958

Figure 1. Contrast-enhanced computed tomography image of the chest showing a pericardial effu- sion, bilateral pleural effusions and pericardial enhancement. There were no indications of aortic dissection or pulmonary thromboembolism (A, B). Chest computed tomography image showing mil- iary tuberculosis (C, D).

specificity. Burgess et al. reported that a prospective follow- up study of 110 patients who had undergone serial pericar- diocentesis in a facility in South Africa showed that 64 pa- tients had tuberculous pericarditis. When the cutoff value for the ADA level was set at 30 IU/L, the sensitivity was 94%, the specificity was 68% and the positive predictive value was 80% (8). Alternatively, Reuter et al. reported that a pericardial fluid lymphocyte: neutrophil ratio of !1hasa sensitivity of 73%, a specificity of 79%, a positive predic- tive value of 86% and a negative predictive value of 81% (6). Therefore, the current diagnostic strategy consists of multifaceted assessments using multiple diagnostic tech- niques. Figure 2. Ziehl-Neelsen staining of acid-fast bacilli in the In the current case, we waited for the PCR results on day pericardial fluid (day 5). Acid-fast bacilli were found in 10 to confirm the diagnosis. Consequently, the initiation of smears of the pericardial fluid. antituberculous drug therapy was markedly delayed. The pa- tient had been living in a low-cost boarding house and may not have been paying sufficient attention to personal hy- pericarditis (4). Only 40-60% of smears obtained from the giene. Therefore, tuberculosis infection should have been pericardiocentesis fluid of patients with tuberculous peri- considered as a possible cause of his condition. In addition, carditis are positive for acid-fast bacilli (4-6). Additionally, if pericardial fluid smears are positive for acid-fast bacilli pericardial fluid culture does not have high sensitivity, al- and the medical and epidemiological history suggests a high though is thought to have 100% specificity (6). Another risk for tuberculosis infection, empirical treatment against method for detecting M. tuberculosis in pericardial fluid is tuberculous pericarditis such as the administration of new DNA amplification using PCR (7). However, detection of quinolone antibacterial drugs should be initiated without tuberculosis through cultures and PCR requires a significant waiting for the results of cultures or PCR. amount of time. Rapid tests evaluating the ADA level or the Hemorrhagic pericardial fluid is found in as many as 80% lymphocyte: neutrophil ratio in pericardial fluid exhibit low of cases of tuberculous pericarditis (9). Atar et al. reported

3199 Intern Med 51: 3197-3201, 2012 DOI: 10.2169/internalmedicine.51.7958

Figure 3. Treatment course. After the administration of antituberculosis therapy (day 10), the pa- tient showed marked improvement. NoA: noradrenaline, DOB: dobutamine, DRPM: doripenem, CEZ: cephazolin, INH: isoniazid, RFP: rifampicin, PZA: pyrazinamide and EB: ethambutol

Table 2. Differential Diagnosis of Hemorrhagic over, up to 90% of patients with tuberculous pericarditis Pericardial Effusion who are left untreated die within the first year due to dis- semination of M. tuberculosis or the development of conges- Etiology No. (%) tive resulting from constrictive pericarditis (11). Iatrogenic 30 (31) Transcatheter intervention, pacemaker insertion 18 (18) Because records of electrocardiographic monitoring were Postpericardiotomy syndrome 12 (13) not maintained, the cause of sudden cardiac arrest in this Malignancy 25 (26) case was unknown. The potential causes of the cardiac arrest Breast cancer 7 (7) include , ventricular or other Lung cancer 5 (6) causes of cardiogenic shock. Diaz-Peromingo et al. reported Lymphoma 6 (6) a case of tuberculous in a patient with HIV and Miscellaneous 7 (7) M. tuberculosis with a prolonged QT interval (12), and Complications of acute 10 (11) Hageman et al. showed that patients with severe chronic tu- Idiopathic 9 (10) berculous pericarditis have an increased frequency of ar- Uremic 7 (7) rhythmia (13). In this case, the sudden onset of lethal ar- Aortic dissection 4 (4) Traumatic 3 (3) rhythmia may have occurred in the ambulance because the Bacterial or para-infectious 2 (2) time until return of spontaneous circulation was short and a Anticoagulant therapy 2 (2) marked improvement in blood pressure was seen immedi- Tuberculosis 2 (2) ately after resuscitation. Therefore, when treating patients Systemic lupus erythematosus 1 (1) with tuberculous pericarditis or tuberculous myocarditis, cli- Rejection post heart transplantation 1 (1) nicians should be aware of the possibility for sudden cardiac Total 96 (100) arrest. We encountered a case of tuberculous pericarditis which was diagnosed using PCR-based detection of M. tuberculo- that hemorrhagic pericardial effusions are most commonly sis in pericardial fluid in which the patient showed marked iatrogenic; however, they are also frequently caused by ma- improvement after the administration of antituberculous lignant disorders (Table 2) (10). Although tuberculosis ac- drugs. This case highlights the importance of considering tu- counts for only 2% of hemorrhagic pericardial effusions, the berculous pericarditis in addition to high-incidence diseases possibility of tuberculosis infection should therefore be in- such as malignant tumors in the differential diagnosis of cluded in the differential diagnosis. hemorrhagic pericardial effusion and being aware that tuber- In the present case, the location of the primary lesion was culous pericarditis or myocarditis can sometimes cause sud- unclear; however, miliary tuberculosis (TB) was detected on den cardiac arrest. chest CT. In general, tuberculous lesions erode into blood vessels, disseminating millions of tubercle bacilli into the The authors state that they havenoConflictofInterest(COI). bloodstream (7) and the , as in this case. More-

3200 Intern Med 51: 3197-3201, 2012 DOI: 10.2169/internalmedicine.51.7958

Diseases of the European Society of Cardiology. Eur Heart J 25: References 587-610, 2004. 8. Burgess LJ, Reuter H, Carstens ME, Taljaard JJ, Doubell AF. The 1. Rooney JJ, Crocco JA, Lyons HA. Tuberculous pericarditis. Ann use of adenosine deaminase and interferon-gamma as diagnostic Intern Med 72: 73-81, 1970. tools for tuberculous pericarditis. Chest 122: 900-905, 2002. 2. Nakamura Y, Obase Y, Suyama N, et al. A small outbreak of pul- 9. Mayosi BM, Burgess LJ, Doubell AF. Tuberculous pericarditis. monary tuberculosis in non-close contact patrons of a bar. Intern Circulation 112: 3608-3616, 2005. Med 43: 263-267, 2004. 10. Atar S, Chiu J, Forrester JS, Siegel RJ. Bloody pericardial effu- 3. Hisada T, Kayakabe K, Ishizuka T, et al. Massive hemoptysis due sion in patients with cardiac tamponade: is the cause cancerous, to pulmonary tuberculosis. Intern Med 44: 156-157, 2005. tuberculous, or iatrogenic in the 1990s? Chest 116: 1564-1569, 4. Fowler NO, Manitsas GT. Infectious pericarditis. Prog Cardiovasc 1999. Dis 16: 323-326, 1973. 11. Schepers GW. Tuberculous pericarditis. Am J Cardiol 9: 248-276, 5. Strang JI, Kakaza HH, Gibson DG, et al. Controlled clinical trial 1962. of complete open surgical drainage and of prednisolone in treat- 12. Diaz-Peromingo JA, Mariño-Callejo AI, González-González C, et ment of tuberculous pericardial effusion in Transkei. Lancet 2: al. Tuberculous myocarditis presenting as long QT syndrome. Eur 759-764, 1988. J Intern Med 11: 340-342, 2000. 6. Reuter H, Burgess L, van Vuuren W, Doubell A. Diagnosing tu- 13. Hageman JH, D’Esopo ND, Glenn WWL. Tuberculosis of the berculous pericarditis. QJM 99: 827-839, 2006. pericardium―a long-term analysis of forty-four proved cases. N 7. Maisch B, Seferovi!PM, Risti!AD, et al. Guidelines on the diag- Engl J Med 270: 327-332, 1964. nosis and management of pericardial diseases executive summary: The Task Force on the Diagnosis and Management of Pericardial

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