Case of the Month:

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Case of the Month

• Is it a Mystery???

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• 32 y/o post-doctoral student at UT, who moved
  from India 3 years ago for academic reasons.
• The patient presents with one month of febrile
  illness (not quantified), general malaise,
  weakness, non-productive cough, weight loss (10
  lbs estimation). Few days prior to admission her
  symptoms have been worsening, as well as new SOB.

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• The SOB is at rest, but it worsens on exertion.
  Denies orthopnea, PND or LE edema.
• Because of her symptoms, she went to Student
  Health, where a CXR was obtained, a PPD was
  placed and PO antibiotics were administered.

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• The CXR preliminary report was read as
  cardiomegaly and suspicious appearing right
  apex.
• The PPD was ().
• The patient was referred from Student Health to
  the Med ED for further evaluation.

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• PMHx malaria when she was 10 yoa
• Otherwise negative
• Soc Hx Denies smoking, ETOH or recreational
  drugs
• Meds Ciprofloxacin 200mg PO BID
• FHx Non-contributory

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• ROS
• Denies CP. Denies SOB prior to current illness.
  Good exercise tolerance.
• Denies frequent cough, in the past. Denies
  hemoptysis. Denies unexplained febrile illness or
  weight loss in the past. Denies night sweats.
• Denies arthralgias or myalgias.

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• Has been a healthy adult until now.

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• PEX
• BP 115/70 HR 105 T 101 F RR 21 SO2 100
• Patient is in mild distress because of
  respiratory difficulty. AAOX3 able to provide
  history.
• () 7 cm JVD, no carotid bruits heard.

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• Heart RR no S3, S4 no murmurs or rubs.
• Lungs Bibasilar crackles, otherwise clear.
• Abd soft, non tender, BS , no guarding.
• NO LE edema.

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• CXR Cardiomegaly. Bilateral pleural effusions.
  NO pulmonary nodules.
• CT scan chest Large pericardial effusion.
  Moderate bilateral pleural effusions. Bilateral
  atelectasis.

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• The cardiology fellow on call, Dr. Z was
  called.
• He noted on his physical exam a pulsus paradoxus
  of 20 mmHg.
• He performed STAT EKG and echo.

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Echocardiogram
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• Na 141 K 3.5 Cl106
• CO2 29 BUN 13 Crea 0.7
• T Prot 6.0 Alb 2.6 Bili 0.7
• SGOT 26 SGPT 63 AlP 175
• GGT 141
• PT 14.7 PTT 34.9 INR 1.16

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• WBC 14.9 (18)K Hgb 11 Hct 33
• Plt 614 K N 77 L 14
• M 9 E 1 MCV 80.9
• MCH 27 RDW 15.1
• Fe 24 TIBC 308
• Ferritin 115

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• CRP 8.1 ESR 98 TSH 1.560
• Anti RNP 36 RF 11.4
• ANA (-) Smith AB 29
• Hep A, B, C (-)

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Pericardial Fluid

• Glucose 41 LDH 2432
• pH 7.5 Protein 6.8
• WBC10.5 K RBC 5.4 K
• N 46 L 14 M 10
• AFB smear (-) Fungal cx (-)
• Aerobic cx (-) AFB cx Pending

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• Adenosine Deaminase 44.4
• PCR for M.tuberculosis (-)

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• Pericardial Biopsy Reactive mesothelial cells,
  underlying adipose tissue and paucicellular fibro
  connective tissue with foci of chronic
  inflammation consistent with chronic
  pericarditis. Granulomatous inflammation is not
  identified.
• Special stains are Pending.

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• Microbiology
• AFB smear (sputum) (-) X 3
• AFB cxs (sputum) Pending
• Blood cxs (-) X3

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SO??
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Tuberculous Pericarditis

• Tuberculous pericarditis occurs in 1 to 2 of
  patients with pulmonary tuberculosis
• Diagnosis of tuberculous etiology in pericardial
  effusions is important since the prognosis is
  excellent with specific treatment.
• Clinical features may not be distinctive and the
  diagnosis could be missed. With the spread of HIV
  infection the incidence has increased.

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• Usually presents as a slowly progressive febrile
  illness. When it presents as an acute
  pericarditis, which is uncommon, or as cardiac
  tamponade, which is frequent, the diagnosis is
  more likely to be delayed or missed.
• The delay from hospital admission to diagnosis
  was 5.2 weeks diagnosis was first made only at
  necropsy in 17 of patients.1,2

1.Sagrista-Sauleda J. Am Coll Cardiol
198827248 2. Rooney JJ. Ann Intern Med
197072738
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• Chronic idiopathic effusions in which no etiology
  could be established are a common cause of
  tamponade varying from 1132.
• Without specific treatment the average survival
  was 3.7 months in a report from Africa and only
  4/20 (20) were alive at six months.

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Pathogenesis

• In a rare case there may be direct spread from
  tuberculous pneumonia, it can be seeded in
  miliary tuberculosis and in such instances other
  organ systems dominate the presentation.
• Most often the spread is from the breakdown of
  infection in mediastinal nodes directly into the
  pericardium and particularly those at the
  tracheobronchial bifurcation.

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• Lymphatic drainage of the pericardium is mainly
  to the anterior mediastinal, tracheobronchial,
  lateropericardial, and posterior mediastinal
  lymph nodes and not into the hilar nodes.
• Does not show up on routine chest radiographs but
  can be seen only on chest computed tomography or
  magnetic resonance imaging (MRI) studies.

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• Sir William Osler concluded that caseous
  mediastinal lymph nodes were the usual focus of
  pericardial involvement.1
• Rooney et al found that 50 of patients with TPE
  who were necropsied had pleural effusion due to
  tuberculous pleuritis.2

1.Spodick DH. Arch Intern Med 19569873749 2.
Rooney JJ. Ann Intern Med 197072738
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• Some authors separate tuberculous pericarditis
  into four stages
• The dry stage
• The effusive stage
• The absorptive phase
• The constrictive phase

Ortbals DW. Arch Intern Med 1979 Feb139(2)231-4
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Diagnosis
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• Characteristics of the pericardial fluid
• The effusion in tuberculous pericarditis is
  straw-colored .
• It is uniformly an exudate. The protein
  concentration is invariably above 3.0 g/dL, and
  is greater than 5.0 g/dL in 50 to 77.
• LDH level is elevated in approximately 75,
  commonly exceeding 500 IU/L.

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• Glucose concentration is usually between 60 and
  100 mg/dL.
• pH is virtually always less than 7.40.
• The nucleated cell count is usually between 1000
  and 6000/mm3. It is lymphocyte-predominant in 60
  to 90 of cases. Lymphocytes predominate in
  subacute and chronic tuberculous effusions, while
  neutrophils predominate in acute effusions.
• The fluid rarely contains more than 5
  mesothelial cells. The presence of more than 10
  eosinophils usually excludes the diagnosis of
  tuberculous pericarditis

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• Only 40 to 60 of patients with tuberculous
  pericarditis who undergo pericardiocentesis have
  acid fast bacilli (which are virtually
  diagnostic) on smear.

Strang JI. Lancet 1988 Oct 12(8614)759-64
Fowler NO. Prog Cardiovasc Dis
1973 16323
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• Polymerase chain reaction (PCR)PCR technology
  has been used for nucleic acid amplification.
  Overall accuracy of PCR approached the results of
  conventional methods. The sensitivity for
  pericardial fluid was poor and false positive
  results with PCR remain a concern.
• Sensitivity in pleural fluid is 42-81.

Cegielskyi JP. J Clin Microbiol 19973532547
Lee JH. Am J Med 200211351921
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• SerodiagnosisELISA A sensitivity of 61 (at 96
  specificity) was achieved. It is unlikely that
  this technology will be widely applied.

NG TT. Q J Med 19958831720
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• Adenosine deaminase
  Adenosine deaminase levels are believed to
  reflect T-cell activity. The levels with TPE have
  varied from 10303 U/l, and with a cut off level
  of 30 U/l the sensitivity was 94 and specificity
  68 with a positive predictive accuracy of 80.1
• High ADA levels that may occur in other
  conditions, like rheumatoid, empyema,
  mesothelioma, lung cancer, parapneumonic, and
  hematologic malignancies.

1. Burgess LJ. Chest 20021229005

2. Komsuogluo B. Eur Heart J 199516112630
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• Interferon-gamma
  Median concentration in
  TPE was gt1000 pg/l and significantly higher than
  malignancy or non-tuberculous effusions
  (plt0.0005). A cut off value of 200 pg/l for
  interferon-gamma resulted in a sensitivity and
  specificity of 100 for the diagnosis of TPE.

Burgess LJ. Chest 20021229005
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• Histological evidenceHistological evidence of a
  tuberculous granuloma with the demonstration of
  acid fast bacilli would be a definite diagnostic
  criterion.
• The typical granuloma is however not always found
  and the pericardial biopsy may show non-specific
  findings even when M tuberculosis is found in the
  pericardial fluid. Strang et al reported 29 of
  non-specific findings on patients whom M
  tuberculosis was recovered from the pericardial
  fluid.

Strang JIG. Lancet 1988ii75964.
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Myocardium with epicardium and part of the
pericardium. In the epi- and pericardium a
granuloma is present (right half of image), with
caseous necrosis, lymphocytes, and epitheloid
cells. The myocardium (left quarter of image) is
not involved in the inflammatory process.
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• Chest computed tomographyEnlarged mediastinal
  lymph nodes gt10 mm detected on chest computed
  tomography have been reported recently in
  virtually 100 of patients with TPE. They were
  found in all 22 patients with TPE and none of a
  control group with large viral/idiopathic or
  postoperative pericardial effusion.

Cherian G. Am J Med 200311431922
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• Features of Mediastinal Nodes in TPE
• Aortopulmonary, paratracheal, and carinal nodes
  most often involved.Typically coalesced (matted)
  with hypodense center.Hilar nodes rare and
  inconspicuous.Nodes seen only on chest computed
  tomography or MRI.Nodes disappear or regress on
  specific treatment.

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• EchocardiographyThe pericardial exudate is thick
  and fibrinous with a tendency to form adhesions
  and in some instances constriction. On
  echocardiography there are patchy deposits with
  "fibrinous" strands criss crossing the
  pericardial space.

LIU PY. Am J Cardiol 20018711335
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• Large pericardial effusion and inversion of the
  right atrium, caused by elevated pericardial
  pressure, in late diastole and early systole.
• A parasternal short-axis view shows that the
  right ventricular outflow tract is compressed in
  diastole because of the elevated pericardial
  pressure.

Nardell E. N Engl J Med 2004 3511804-1805
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• Culture of mycobacterium tuberculosisRecovery
  from the pericardial fluid has varied from
  30100. Strang using special techniques was
  able to culture M tuberculosis from all patients.
  The specimens were cultured in double strength
  Kirchner culture medium after bedside inoculation
  and also conventional culture in Stonebrink
  medium.

Strang JIG. J Infect 1994282514.
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• Role of corticosteroids
• In active constrictive pericarditis, the
  addition of corticosteroids to standard
  antituberculous chemotherapy reduced mortality
  and the need for subsequent pericardiocentesis.
• A similar effect is observed on pericarditis
  with effusion, when coupled by initial
  pericardial drainage.
• Prednisone 60 mg/day for four weeks, 30 mg/day
  for four weeks, 15 mg/day for two weeks, then 5
  mg/day for week eleven.

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• SUGGESTED APPROACH
• Ascertain if there is a prior history of
  tuberculosis, tuberculosis exposure, of prior PPD
  skin test reactivity, or if the patient is
  immunocompromised.
• Perform an intermediate strength PPD skin test on
  all patients
• If the PPD skin test is positive or the patient
  is immunocompromised and an alternate cause (eg,
  lupus, malignancy, trauma) is not present,
  empiric antituberculous and prednisone therapy
  can be initiated.
• If, however, there is hemodynamic impairment,
  subxiphoid pericardial biopsy and sampling of
  pericardial fluid should be performed.
• If the biopsy shows granulomatous changes and/or
  AFB, smear of the pericardial fluid is positive
  for AFB, or the probability of tuberculosis is
  highly likely.

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Place you bets!!
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Thank you!