Interesting Case Rounds Nicole Kirkpatrick February 7, 2008

Case 25 y.o. first nations male CC: RUQ pain and SOB

HPI SOBOE X 4 weeks, gradually worsening Cough RUQ pain X 3 days Constant pain, non-radiating No nausea, vomiting or diarrhea No peripheral edema, no orthopnea No recent travel, no sick contacts Not immunocompromised Fever, night sweats and weight loss

HPI PMH - healthy PSH - none Medications - none Allergies - none Smoker ETOH -15 beers/w Marijuana use

Vital signs HR 105 BP 110/80 RR 25 T 38 SpO2 98% on R/A

Physical exam Thin, no icterus noted CVS JVP ~8cm, does not vary with respiration Normal S1, S2, no extra HS appreciated Decrease in SBP of 8mmHg on inspiration Mild peripheral edema RESP Clear ABD Soft Liver edge palpable ~4 cm below CM Tender in RUQ Spleen not palpable No peritoneal findings No shifting dullness

Investigations?

Investigations Blood work Hb normal WBC slightly elevated Normal electrolytes Normal renal function ALT slightly elevated

Investigations ECG Sinus tachycardia Low voltage

Investigations CXR

Chest X-ray

Thoughts?

Differential Infection Viral (coxsackie A,B, HIV, Hepatitis), Bacterial (pneumococcus, streptococcus, staphylococcus, TB,Neisseria,Legionnella), Fungal (histoplasmosis, coccidioidomycosis), Parasitic Inflammation RA, SLE, AS, Scleroderma, ARF, Wegner’s Metabolic Uremia, Hypothyroidism Neoplastic Primary or Metastatic (Lung, Breast, Lymphoma, Leukemia) Drug-related Procainamide, INH, Hydralazine, Minoxidil, Phenytoin) Irradiation Trauma Dressler’s

Initial management

Management Transferred to larger centre for definitive diagnosis ECHO Pericardiocentesis Pericardial biopsy

Diagnosis Tuberculous pericarditis

Objectives Review TB TB pericarditis Epidemiology Presentations Diagnosis Treatment

Mycobacterium tuberculosis

Tuberculosis Mycobacterium tuberculosis Other Mycobacterium spp. Aerobic, non-spore forming, slow growing bacillus Humans are the only reservoir Other Mycobacterium spp.

World Incidence of TB Incidence per 100,000 pop / year > 300 100 - 299 50 - 99 25 - 49 < 24 No data Source: 2005 WHO (maps.maplecroft.com)

Tuberculosis Primary infection Latent TB Reactivation Infected through droplet transmission Host defenses kill bacteria and prevent active disease Latent TB Due to bacilli that survive host defenses and are carried to LN where they can survive for years Reactivation Occurs when host immune system is not capable of containing foci of latent infection

Tuberculosis and HIV Increased risk of: Primary disease becoming active infection Reactivation 5-10% per year Extrapulmonary TB

WHO Estimates of TB (2005) Incidence: 8.8 million worldwide Canada 5 cases / 100,000 (1616 total) Prevalence: 14 million

Tuberculous Pericarditis Leading cause of pericarditis in African and Asia Occurs in 1-2% of patients with pulmonary TB Commonly due to reactivation with no obvious primary focus Accounted for 70% of cases referred for diagnostic pericardiocentesis in SA series 4% in the developed world

Tuberculous Pericarditis Pericardium involved via Retrograde lymphatic spread Peritracheal, peribronchial, mediastinal LN Contiguous spread from adjacent lesion Lung, pleurae, ribs, diaphragm, peritoneum Hematogenous spread

Tuberculous Pericarditis Four pathological stages DRY Isolated granulomas EFFUSIVE Serosanginous effusion with lymphocytic exudate ABSORPTIVE Absorption of effusion and resolution of symptoms without treatment CONSTRICTIVE Fibrosis of visceral and parietal pericardium +/- effusion

Tuberculous Pericarditis Mortality 80-90% in pre-antibiotic era 8-17% in HIV negative patients 17-34% in HIV positive patients

Tuberculous Pericarditis Three clinical presentations Pericardial effusion (80%) Constrictive pericarditis (5%) 30-60% of patients progress to constrictive pericarditis Effusion-constriction (15%)

Tuberculous Pericarditis Effusion Bacilli penetrate pericardium Antigens on bacilli initiate a delayed hypersensitivity reaction Lymphocytes release cytokines that activate MP and induce granuloma formation Often few bacilli found in pericardial fluid

Tuberculous Pericarditis Symptoms Cough Dyspnea CP Night sweats Orthopnea Weight loss Signs Tachycardia Fever JVD HSM Ascites Edema

Tuberculous Pericarditis Effusion Tamponade Pulsus paradoxus Friction rub Indistinct apical impulse Distant heart sounds Constriction Kussmaul’s Pericardial knock Effusive-constriction Often apparent when RA pressure remains elevated after fluid removal

Diagnosis Can be challenging Consider in patients Pericarditis that does not resolve From TB endemic areas Work or Travel in endemic areas High risk populations

Diagnosis ECG Non specific changes Low QRS voltage Diffuse T wave inversion Electrical alternans if large effusion Minority can present with acute ST and PR changes of acute pericarditis CXR May show pulmonary lesion Increased cardiac silhouette with pericardial effusion Pleural effusion Pulmonary venous congestion rare

Diagnosis ECHO Effusion Constriction Fibrinous strands RA compression, RV diastolic collapse, abN respiratory variation in tricuspic and mitral flow velocities, dilated venae cavae Constriction Pericardial thickening Abnormal ventricular septal movement

Diagnosis Tuberculin Skin Test Can be negative in up to 30% due to anergy

Diagnosis Pericardiocentesis and analysis of fluid Exudative effusion AFB on smear (40-60%) Culture Other PCR for Mycobacterium DNA Elevated adenosine deaminase Interferon gamma using ELISA

Diagnosis Pericardial biopsy Stain tissue for AFB Histology Granulomatous inflammation

Treatment Anti-tuberculous treatment Early studies with Streptomycin showed decreased mortality and progression to constriction INH, Rifampin, Pyrazinamide, Ethambutol X 2M INH, Rifampin X 4M

Quiz Multi-drug resistant TB (MDR-TB) Resistant to INH and RIFAMPIN Extensively drug resistant TB (XDR-TB) Resistant to INH and RIFAMPIN and to 3 of the 6 main classes of second line agents Aminoglycosides, polypeptides, fluoroquinolones, thioamides, cycloserine, paraaminosalicyclic acid

Treatment Steroids Still controversial Decrease mortality, need for pericardiectomy

Treatment Pericardiectomy After initiation of anti-tuberculous treatment

Back to the case Found to have Effusive-Constrictive Pericarditis TB skin test negative Started on anti-tuberculous treatment Underwent pericardiectomy Technically difficult, not able to completely remove pericardium On-going difficulty with HF Work-up for transplant

Questions or Comments?

References Cherian, G. (2004). "Diagnosis of tuberculous aetiology in pericardial effusions." Postgrad Med J 80(943): 262-6. Mayosi, B. M., L. J. Burgess, et al. (2005). "Tuberculous pericarditis." Circulation 112(23): 3608-16. Mayosi, B. M., C. S. Wiysonge, et al. (2006). "Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry." BMC Infect Dis 6: 2. Nardell, E. A., D. Fan, et al. (2004). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 22-2004. A 30-year-old woman with a pericardial effusion." N Engl J Med 351(3): 279-87. Strang, J. I., A. J. Nunn, et al. (2004). "Management of tuberculous constrictive pericarditis and tuberculous pericardial effusion in Transkei: results at 10 years follow-up." Qjm 97(8): 525-35. Syed, F. F. and B. M. Mayosi (2007). "A modern approach to tuberculous pericarditis." Prog Cardiovasc Dis 50(3): 218-36. Wragg, A. and J. I. Strang (2000). "Tuberculous pericarditis and HIV infection." Heart 84(2): 127-8. UpToDate eMedicine