An Unusual Case of Postpartum Dyspnea Avinash Ramdass, MD; Tauseef Qureshi, MD; Jasdip Matharu, MD; James Cury, MD; and Vandana Seeram, MD
A 40-year-old South Asian woman was admitted in active labor at 38 weeks’ gestation. She had an unremarkable medical history with routine prenatal care, negative HIV testing results, and an uneventful pregnancy. She received a Bacillus Calmette-Guérin vaccine during childhood and reportedly had a subsequent positive puriﬁed protein-derivative test result 1 year prior to conception. She never smoked and had seven normal term pregnancies. CHEST 2015; 147(2):e38-e43
On her first postpartum day, after an uncomplicated delivery, she complained of mild central chest pain and dyspnea and was noted to be febrile at 38.3°C. She was empirically treated for suspected postpartum endometritis by the obstetric team. Initial workup results, including a portable chest roentgenogram (CXR), urine cultures, and blood cultures, were negative for other sources of infection. On postpartum day 3, she developed progressive dyspnea with two-pillow orthopnea and worsened central chest pain. She was hypotensive (BP, 80/40 mm Hg); tachycardic (heart rate, 120 beats/min); and tachypneic, with oxygen saturation via pulse oximetry of 97% on room air; with a worsening fever of 39.7°C. Examination findings included an elevation in her jugular venous pulsation, muffled heart sounds with a regular cardiac rhythm, radial pulsus alternans, and peripheral pitting leg edema. Lung examination revealed diminished bibasilar air entry, bronchial breath sounds, and bilateral crackles. A CXR on day 3 showed a globular-shaped heart, small bilateral pleural effusions, Kerley B lines, and upper lobe and hilar vascular prominence (Fig 1A). An ECG showed sinus rhythm, low voltage QRS complexes in the inferior leads, and electrical alternans (Fig 1B). A bedside echocardiogram confirmed the presence of a
Manuscript received April 12, 2014; revision accepted September 16, 2014. AFFILIATIONS: From the Department of Pulmonary and Critical Care (Drs Ramdass, Matharu, Cury, and Seeram), University of Florida College of Medicine, Jacksonville, FL; and University of South California, Pulmonary and Critical Care (Dr Qureshi), Los Angeles, CA. CORRESPONDENCE TO: Avinash Ramdass, MD, Department of Pulmonary and Critical Care, University of Florida College of Medicine,
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large, circumferential, pericardial effusion that measured 3.2 cm in its largest dimension with . 25% respiratory variation of transmitral flow (Fig 1C, Video 1). Strands and echogenic densities were noted in the pericardial fluid, suggesting an exudative process. The inferior vena cava was enlarged and lacked normal respiratory variation. An emergency pericardiocentesis was performed with the removal of 850 mL of serosanguinous pericardial fluid, which restored hemodynamic stability. Pericardial fluid analysis was remarkable for a WBC count of 4,733 cells/mL with a lymphocyte predominance (91%) and an RBC count of . 70,000 cells/mL. Cytologic evaluation revealed numerous small lymphocytes, rare reactive mesothelial cells, and fibrin. The lymphocyte analysis showed a mixed population of T (CD3 positive), and B (CD20 positive) cells with negative cyclin D1, consistent with a reactive nonneoplastic process. Periodic acid-Schiff, Gomori-Grocott methenamine silver, and gram stains were negative. A hematoxylin-and-eosin stain revealed a homogenous collection of lymphocytes (Fig 1D). Further biochemical analysis of the pericardial fluid confirmed our clinical suspicion.
Figure 1 – A, Portable erect chest roentgenogram showing a globular heart, moderate-sized bilateral pleural effusions, increased interstitial lung markings, and hilar prominence. B, ECG showing electrical alternans and low-voltage complexes in the inferior leads. C, Two-dimensional echocardiogram demonstrating large pericardial effusion measuring 3.2 cm at lateral wall of the left ventricle, 2.4 cm at the right atrium, and 3 cm anterior to the right ventricle free wall. Right ventricle and right atrium collapse was noted (Video 1). D, Hematoxylin-and-eosin-stained cytospin preparation of pericardial fluid revealing numerous reactive lymphocytes and few mesothelial cells (original magnification 3 200).
What is the diagnosis?
Diagnosis: Effusive pericardial TB presenting as cardiac tamponade, exacerbated by postpartum immune reconstitution syndrome Discussion A mycobacterial TB complex (MTB) polymerase chain-reaction (PCR) test of the pericardial fluid was positive and several acid-fast mycobacterial forms were seen on a cell block specimen of pericardial fluid (Fig 2). Clinical Discussion
Tuberculous pericarditis accounts for only 1% to 2% of cases of pericarditis in developed countries and remains an uncommon etiology for severe pericardial effusion and manifestation, as cardiac tamponade is rare.1 Bacillus Calmette-Guérin vaccination provides approximately 60% protection against the development of pulmonary TB, with greater protection against tuberculous meningitis and disseminated TB. This waning immunity lasts 10 to 15 years.2 Latent TB infection in pregnancy mirrors that of the general population and is up to 10 times higher in foreign-born Americans, including pregnant women, regardless of HIV status.3 The differential diagnosis of postpartum chest pain, dyspnea, fever, and hypotension is broad and includes both pregnancy- and nonpregnancy-related etiologies. Infectious causes such as endometritis, pneumonia, and septic pelvic thrombophlebitis, and cardiorespiratory causes such as pulmonary thromboembolism, peripartum cardiomyopathy, acute myocardial infarction, mitral valve rupture, amniotic fluid embolism, aortic dissection, and systemic lupus erythematosus flare. This
Figure 2 – Acid-fast stain performed on the cell block prepared from the pericardial fluid revealed several acid-fast positive mycobacterial forms (two mycobacteria are visible in the photomicrograph) (original magnification 3 600).
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patient’s presentation is a manifestation of cardiac tamponade as a result of tuberculous pericarditis. The clinical findings of tachycardia, elevated jugular venous pulsation, muffled cardiac sounds, and pulsus alternans are not limited to but should point toward cardiac tamponade with sensitivities of 77%, 84%, 94%, and 36%, respectively. Other signs may include pulsus paradoxus, pericardial knock, hepatomegaly, and edema.4 Peripartum TB is a rare but important differential diagnosis of postpartum fever.5 The nonspecific symptoms may be attributed to late pregnancy and the diagnosis can be overlooked. As a result of the relative immunosuppression that occurs during pregnancy, tuberculin skin tests can be negative in pregnant women with TB, even in those with recent exposure to TB.6 During pregnancy, there is progressive suppression of lymphocytic reactivity toward the purified protein derivative of tuberculin, indicating pregnancy-associated depression of cell-mediated immunity.7 Placental products such as progesterone, prostaglandin E2, IL-4, and IL-10 can impair the T-helper (Th) immune response.8 After delivery, the lymphocytic proliferative response rapidly returns to normal as early as 24 h, and complete recovery occurs at 4 weeks’ postpartum.7 Th1 suppression reverses and symptoms are exacerbated like other reconstitution syndromes similar to highly active antiretroviral therapy in HIV treatment.9 Women in the early postpartum stage are twice as likely to develop TB as nonpregnant women.10 The median time from delivery to the onset of symptoms is 4 to 10 days.5 The diagnosis of isolated MTB pericarditis must be confirmed by a positive smear, culture, or MTB PCR from pericardial fluid or biopsy specimen. Pericardial fluid smear for acid-fast bacilli is positive from 0% to 42% in people with MTB pericardial effusions. Pericardial fluid culture is more likely to confirm MTB than pericardial histology. The sensitivity of pericardial biopsy specimen histology ranges from 10% to 64%, while MTB PCR on pericardial biopsy specimens has a sensitivity of 80%. This is much higher than the sensitivity of pericardial fluid MTB PCR, which is positive in 15% of tuberculous pericarditis.4 Antituberculous chemotherapy increases survival dramatically in tuberculous pericarditis.4 The effectiveness of treatment with corticosteroids in tuberculous pericarditis is controversial but likely to be most beneficial for patients with constrictive pericarditis.11 Constriction develops in 18% to 46% of patients despite prompt treatment, with an average time ranging from
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6 months to 2 years.12 There is no clear evidence to identify patients who will progress to constriction, but it is suggested by effusive disease with fibrin stranding and a positive pericardial fluid microbiology at diagnosis. High pericardial adenosine deaminase levels show a positive correlation, but data are limited.12 Patients should be followed symptomatically and evaluated with echocardiography for development of constriction. Pericardiectomy is warranted in the setting of constrictive pericarditis and constrictive-effusive pericarditis despite antituberculous therapy, especially when there are pericardial calcifications.13 The choice of surgical intervention depends upon the clinical condition of the patient, as the mortality of pericardiectomy approaches 19%. In such cases, a pericardial window can be done for recurrent pericardial effusions.14 The treatment of active mycobacterial TB complex infection in pregnancy is the same as for nonpregnant individuals and progression is rare, provided that there is compliance with drug therapy.15 There is currently no consensus for treatment of latent TB infection (LTBI) in pregnancy. For pregnant women who are HIV negative and who have LTBI, the World Health Organization does not comment on whether to offer isoniazid during pregnancy and the US Centers for Disease Control and Prevention recommends delaying treatment until 2 to 3 months postpartum. Both organizations recommend early treatment of LTBI in HIV-positive pregnancies.16 All first-line and second-line agents are pregnancy class C with the exception of the aminoglycosides and fluoroquinolones, which are class D. Breastfeeding should not be discouraged for women being treated with the first-line antituberculous drugs because the concentrations of these drugs in breast milk are too small to produce toxicity in the nursing newborn.17 Radiologic Discussion
CXR will usually show a globular-shaped heart and pleural effusions in 90% of cases consistent with pericarditis and pericardial effusion. On a well-penetrated lateral CXR, the presence of pericardial fluid is also suggested by a pericardial fat stripe, which is a radiolucent fat line within the cardiopericardial silhouette.18 Echocardiographic findings of effusion with fibrinous strands on the visceral pericardium are typical but not specific for a tuberculous pathogenesis.4 Other findings include “swinging” of the heart within the effusion, diastolic collapse of the right atrium, right ventricle, left atrium, and, less commonly, the left ventricle, due to equalization and reversal of transmural pressures, as seen in
this patient.19,20 Findings of a dilated inferior vena cava with , 50% collapse during forced inspiration indicates an elevated central venous pressure consistent with cardiac tamponade physiology.21 CT scan of the chest can also be used to identify a pericardial effusion, but in the acute setting, an echocardiogram is preferred due to its diagnostic and therapeutic value for detecting cardiac tamponade physiology. Cavitary lesions, scarring, lymphadenopathy, and other radiologic stigmata of TB, seen on chest CT scan, which can be missed on up to 30% of CXRs, can suggest TB as a cause for pericarditis.22 CT scan of the chest of this patient, after emergent pericardiocentesis, demonstrated pericardial thickening and mediastinal lymphadenopathy with sparing of the hilar nodes (Fig 3); however, no parenchymal changes associated with TB were seen. Findings of low-density rim enhancing lymph nodes strongly suggest tuberculous lymphadenopathy.23 MRI may also be used and has the added advantage of assessing the extent of pericardial inflammation and myocardial involvement.13 Fluorodeoxyglucose-PET CT scan can be used to differentiate between acute tuberculous pericarditis from idiopathic pericarditis based on the degrees of fluorodeoxyglucose uptake in the pericardium and the mediastinal and supraclavicular lymph nodes.12 Pathologic Discussion
Pericardial involvement usually develops by retrograde lymphatic spread of mycobacteria from mediastinal lymph nodes or by hematogenous spread from the site of primary infection.4 A delayed hypersensitivity reaction to the protein antigens of viable acid-fast bacilli penetrating the pericardium is responsible for the formation of tuberculous pericarditis and is largely mediated by Th1 lymphocytes.4 Several pathologic stages may be recognizable in the natural history of tuberculous pericarditis: (1) initial polymorphonuclear leukocytosis and fibrinous exudate with abundant mycobacteria and early granuloma formation; (2) serosanguinous effusion with a predominantly lymphocytic exudate with monocytes and foam cells; (3) absorption of effusion with organization of granulomatous caseation and pericardial thickening caused by fibrin organization; and (4) fibrosis of the visceral and parietal pericardium causing constrictive pericarditis, in turn causing impaired diastolic filling.9 The immune status of a patient may affect the histologic pattern of TB pericardial effusion with less or no granuloma formation in immune-compromised states.4 Light’s criteria for an exudative pleural effusion are likely to have the same clinical significance in pericardial e41
Figure 3 – A, B, Chest CT scan showing (A) enlarged low-density ring enhancing lymphadenopathy and (B) enlarged mediastinal and perivascular lymphadenopathy and pericardial thickening.
effusions.4 Tuberculous pericardial effusions are thus typically exudative and characterized by high protein content and an increased leukocyte count with a predominance of lymphocytes and monocytes.24 In one study, a pericardial lymphocyte to neutrophil ratio ⱖ 1.0 had high sensitivity, specificity, and positive predictive value for diagnosis of a tuberculous cause of pericardial effusion (73%, 79%, and 86%, respectively).24 However, other causes of pericardial exudate need to be excluded, such as bacterial infections other than mycobacteria and fungal agents. Also, the presence of numerous lymphocytes may raise suspicion for lymphoma or other malignancies for which further testing for immunohistochemical markers and flow cytometry on fresh specimens may be required. Measurement of pericardial fluid adenosine deaminase levels . 35 U/L has a sensitivity of 90% and specificity of 74%.4 A pericardial lysozyme level, when elevated, has a sensitivity of 100% and specificity of 91% in MTB pericardial effusions. And finally, interferon g measured by radioimmunoassay, when elevated, has a sensitivity of 92% but a specificity of 100% in MTB pericardial effusions.4
Conclusions Effusive tuberculous pericarditis is an uncommon but important differential diagnosis of postpartum fever, especially in endemic areas, and presentation with pericardial tamponade carries a high mortality risk. Prompt clinical and radiologic diagnosis of tamponade and immediate pericardiocentesis restored this patient’s hemodynamics. She was treated with a four-drug anti-MTB regimen and corticosteroids along with vitamin B6. There was dramatic improvement of symptoms. A CXR showed radiographic resolution of pleural effusions and an echocardiogram repeated 1 week after treatment confirmed resolution of the pericardial effusion. e42 Chest Imaging and Pathology for Clinicians
She is being followed closely for development of recurrent pericardial effusions and constriction, none of which have occurred thus far.
Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/ organizations whose products or services may be discussed in this article. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met. Additional information: The Video can be found in the Multimedia section of the online article.
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12. Dong A, Dong H, Wang Y, Cheng C, Zuo C, Lu J. (18)F-FDG PET/CT in differentiating acute tuberculous from idiopathic pericarditis: preliminary study. Clin Nucl Med. 2013;38(4):e160-e165. 13. Syed FF, Mayosi BM. A modern approach to tuberculous pericarditis. Prog Cardiovasc Dis. 2007;50(3):218-236. 14. Olsen PS, Sørensen C, Andersen HO. Surgical treatment of large pericardial effusions. Etiology and long-term survival. Eur J Cardiothorac Surg. 1991;5(8):430-432. 15. Jana N, Barik S, Arora N, Singh AK. Tuberculosis in pregnancy: the challenges for South Asian countries. J Obstet Gynaecol Res. 2012; 38(9):1125-1136. 16. Centers for Disease Control and Prevention. Latent tuberculosis infection: a guide for primary health care providers. Centers for Disease Control and Prevention website. http://www.cdc.gov/tb/ publications/LTBI/treatment.htm. Accessed March 28, 2012. 17. Blumberg HM, Burman WJ, Chaisson RE, et al; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167(4): 603-662.
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