86. Case Report: Histoplasmosis Pericarditis Complicated by Cardiac Tamponade – Georgetown University

CardioNerds (Amit Goyal & Daniel Ambinder) join Georgetown University/Washington Hospital Center cardiology fellows (Nitin Malik, AJ Grant, and Tsion Aberra) for some fresh Maryland blue crab cakes at the Georgetown waterfront in Washington, DC. They discuss a rare case of histoplasmosis pericarditis complicated by cardiac tamponade. Dr. Patrick Bering provides the E-CPR and program director Dr. Gaby Weissman provides a message for applicants. Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.  

Jump to: Patient summaryCase mediaCase teachingReferences

CardioNerds (Amit Goyal & Daniel Ambinder) join Georgetown University/Washington Hospital Center cardiology fellows (Nitin Malik, AJ Grant, and Tsion Aberra) for some fresh Maryland blue crab cakes at the Georgetown waterfront in Washington, DC. They discuss a rare case of histoplasmosis pericarditis complicated by cardiac tamponade. Dr. Patrick Bering provides the E-CPR and program director Dr. Gaby Weissman provides a message for applicants. Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.
Episode graphic by Dr. Carine Hamo

The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus.

We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director.

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Patient Summary

A woman in her early 30s with a history of Crohn’s disease on TNF-inhibitor therapy and chronic prednisone presented to the ED after two months of abdominal pain and fevers. She was found to have a perforated bowel and taken to emergent surgery and eventually found to have disseminated histoplasmosis. Post-surgery, her hypotension worsened. At this point, the Georgetown University Cardionerds were involved. Listen to the podcast now to learn about histoplasmosis, it’s cardiac involvement, and management of acute effusive pericarditis!


Case Media

A. Left: Admission chest x-ray (PA film), which was overall unremarkable. Right: Chest x-ray from hospital day 12 – which revealed pulmonary edema with bilateral perihilar haziness, increased prominence of pulmonary vascularity, and small-moderate bilateral pleural effusions. Note increased size of cardiac silhouette. At the corresponding time, pericardial effusion (without tamponade) had been diagnosed.
B. EKG: Sinus tachycardia and low-voltage QRS complexes.
C. CT abdomen/pelvis on hospital day 14. Free air noted within the abdomen (left). Moderate pericardial effusion also incidentally appreciated (right).
D. Pulse-Wave Doppler of mitral inflow. Flow variation is present, but variation is less than <30%.
E. (A) Small bowel resection showing focal mucosal ulceration, serositis, and formation of a granuloma. (B) Transmural inflammation seen on small bowel resection. (C) Pathology of ileocecectomy showing focal histoplasmosis characterized by intracytoplasmic yeast-like forms (black circles)

Parasternal short axis view on echocardiogram showing a moderate pericardial effusion without diastolic septal flattening.
Apical view showing profound tachycardia but without chamber collapse. Ejection fraction was moderately reduced.
Parasternal short axis view on echocardiogram showing a moderate pericardial effusion with intermittent septal flattening.
Apical view showing early diastolic RV chamber collapse. 

Episode Schematics & Teaching

The CardioNerds 5! – 5 major takeaways from the #CNCR case

  1. How does one diagnose acute pericarditis? What are the most common etiologies?
    1. Based on the 2015 ESC guidelines on pericardial disease, acute pericarditis is diagnosed when at least two of the following four criteria are present:
      1. Chest pain characteristic of pericarditis
        1. Acute onset, improves with leaning forward, pleuritic
      2. Pericardial rub
      3. EKG changes consistent with pericarditis
        1. PR depressions, ST segment elevation though depending on time course these can normalize or become T wave inversions
      4. New or worsening pericardial effusion
    2. Etiology can vary by geography. In most developed countries, viruses are thought to be the most common cause, though even when a viral cause is suspected, the majority of cases end up being idiopathic. Other etiologies include bacterial (TB is the most common cause of pericarditis in developing countries), autoimmune, hypothyroidism, malignancy, radiotherapy-induced, and immune checkpoint inhibitor-associated pericarditis.
  2. How does one medically manage acute pericarditis? What are the possible treatment strategies? What about recurrent pericarditis?
    1. High dose NSAIDs are typically used as first line treatment in acute pericarditis, though kidney disease and GIB are common comorbidities that can complicate their use. In patient with risk factors for GIB (e.g. age >65, history of PUD) a PPI should be added for gastrointestinal protection. In patients with concomitant CAD, aspirin is often preferred. NSAIDs are often used for 1-2 weeks until symptoms resolve and/or CRP normalizes, after which they should be tapered off. Multiple RCTs, including the COPE and ICAP trials, support the addition of colchicine to NSAIDs to reduce symptoms and recurrence. Colchicine is typically given for 3 months after an acute episode.
    2. Corticosteroids can also be used as 2nd or 3rd line treatment for acute pericarditis, but they have been associated with longer course of disease and higher recurrence rates in meta-analyses. To reduce this risk, low dose steroids are preferred (i.e. prednisone 0.2-0.5 mg/kg/day) and they should be slowly tapered after symptoms resolve and CRP normalizes with close CRP monitoring to detect recurrence. Steroids can be beneficial as first line therapy in cases of autoimmune or immune checkpoint inhibitor-associated pericarditis.
    3. In patients with a lack of response to initial therapy with NSAIDs + colchicine, further workup might be required as these treatments are most effective in viral or idiopathic pericarditis. Treatment failure could indicate the presence of bacterial or malignant pericarditis, which often do not respond to the typical anti-inflammatories.
    4. In patients with recurrence of symptoms after resolution, multiple clinical trials, including the CORE and CORP trials, support the use of colchicine for recurrent pericarditis. Low dose steroids as described above are also often used in patients who had recurrence with first line therapy.
    5. Immunologic therapies like anakinra, an IL-1 antagonist, have shown benefit in RCTs even in patients who are resistant to colchicine and steroid dependent. In the recently published phase III RHAPSODY trial, rilonacept (an IL-1alpha and IL-1beta cytokine trap) led to resolution of recurrent pericarditis compared to placebo.
  3. How should pericardial effusions be managed in the setting of acute pericarditis? When should you consider draining a pericardial effusion?
    1. When a pericardial effusion is detected, the first step should be determining the size and hemodynamic significance with physical exam and echocardiography. For more on the relevant physical exam and echo findings, please see the show notes for Episode 72 on effusive-constrictive pericarditis! Hemodynamically significant effusions require urgent consultation for drainage. In this situation, pericardial drainage catheters should be left in place until drainage ceases, which improves apposition of the pericardial layers and reduces recurrence.
    1. Pericardiocentesis for diagnostic purposes is not routinely recommended. Patients who are resistant to initial treatment, or in whom a bacterial or neoplastic cause is suspected, should undergo pericardiocentesis with diagnostic studies to identify the underlying etiology.
  4. What is histoplasmosis? How does it usually present? What is the difference between histoplasmosis and disseminated histoplasmosis? How common in pericardial involvement?
    1. Histoplasma capsulatum is a dimorphic fungus and the most prevalent endemic mycosis in the US. Endemic to the Ohio and Mississippi River valleys, it is inhaled into the lungs as a mold where it will become a yeast in tissues at 37 degrees C. Once it the lungs it is consumed by macrophages leading to lymphatic and eventually hematogenous spread. Even with systemic spread, most cases are asymptomatic, but approximately 1 in 2000 cases can result in a severe infection. Most cases of severe infection occur in those with high-inoculum exposure, the elderly, or severely immunocompromised as T-cells and TNF play a vital role in host immune response.
    2. When symptoms do arise, they are usually mild, self limited, and resolve without treatment. The most common symptoms are fever, chills, myalgias, cough, pleuritic chest pain, and headache.
    3. Even among severe infections, isolated pulmonary manifestations are most common. When infection spreads to other organ systems outside of the lungs it is labeled disseminated histoplasmosis.
    4. Pericarditis associated with histoplasmosis is uncommon and occurs in around 5-10% of cases. It is most common in pulmonary histoplasmosis and is thought to be primarily an inflammatory response to the pulmonary disease rather than an invasion of the infection in to the pericardium.
  5. How is disseminated histoplasmosis treated? How does this differ from pulmonary histoplasmosis?
    1. Histoplasmosis can affect a wide range of organ systems including skin, GI tract, brain, bone marrow, and lungs. Most patients with isolated pulmonary symptoms or even disseminated histoplasmosis have minimal symptoms and the infection is self-limited and doesn’t require treatment.
    2. Patients with mild to moderate symptoms, either acute pulmonary histoplasmosis that does not resolve or mild to moderate disseminated histoplasmosis, can be treated with azole therapy (e.g., itraconazole). Liposomal amphotericin B is required for patients with severe symptoms regardless of location. After improvement in clinical status, patients can be transitioned to azole therapy to complete 12 months of treatment, though some patients with chronic disease require 18-24 months of therapy.
    3. Pearl: The differential for hyperferritinemia (greater than 10,000) should include disseminated histoplasmosis.

References

  1. Adler, Y., Charron, P., Imazio, M., Badano, L., Barón-Esquivias, G., Bogaert, J., Brucato, A., Gueret, P., Klingel, K., Lionis, C., Maisch, B., Mayosi, B., Pavie, A., Ristić, A. D., Sabaté Tenas, M., Seferovic, P., Swedberg, K., Tomkowski, W., ESC Scientific Document Group, … Nesukay, E. (2015). 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. European Heart Journal, 36(42), 2921–2964. https://doi.org/10.1093/eurheartj/ehv318
  2. Assi, M. A., Sandid, M. S., Baddour, L. M., Roberts, G. D., & Walker, R. C. (2007). Systemic Histoplasmosis: A 15-Year Retrospective Institutional Review of 111 Patients. Medicine, 86(3), 162–169. https://doi.org/10.1097/md.0b013e3180679130
  3. Brucato, A., Imazio, M., Gattorno, M., Lazaros, G., Maestroni, S., Carraro, M., Finetti, M., Cumetti, D., Carobbio, A., Ruperto, N., Marcolongo, R., Lorini, M., Rimini, A., Valenti, A., Erre, G. L., Sormani, M. P., Belli, R., Gaita, F., & Martini, A. (2016). Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA, 316(18), 1906. https://doi.org/10.1001/jama.2016.15826
  4. Chiabrando Juan Guido, Bonaventura Aldo, Vecchié Alessandra, Wohlford George F., Mauro Adolfo G., Jordan Jennifer H., Grizzard John D., Montecucco Fabrizio, Berrocal Daniel Horacio, Brucato Antonio, Imazio Massimo, & Abbate Antonio. (2020). Management of Acute and Recurrent Pericarditis. Journal of the American College of Cardiology, 75(1), 76–92. https://doi.org/10.1016/j.jacc.2019.11.021
  5. Klein AL, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, Insalaco A, LeWinter M, Lewis BS, Lin D, Luis SA, Nicholls SJ, Pano A, Wheeler A, Paolini JF; RHAPSODY Investigators. Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis. N Engl J Med. 2021 Jan 7;384(1):31-41. doi:10.1056/NEJMoa2027892.
  6. Imazio, M., & Adler, Y. (2013). Management of pericardial effusion. European Heart Journal, 34(16), 1186–1197. https://doi.org/10.1093/eurheartj/ehs372
  7. Imazio, M., Belli, R., Brucato, A., Cemin, R., Ferrua, S., Beqaraj, F., Demarie, D., Ferro, S., Forno, D., Maestroni, S., Cumetti, D., Varbella, F., Trinchero, R., Spodick, D. H., & Adler, Y. (2014). Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): A multicentre, double-blind, placebo-controlled, randomised trial. The Lancet, 383(9936), 2232–2237. https://doi.org/10.1016/S0140-6736(13)62709-9
  8. Imazio, M., Bobbio, M., Cecchi, E., Demarie, D., Pomari, F., Moratti, M., Ghisio, A., Belli, R., & Trinchero, R. (2005). Colchicine as first-choice therapy for recurrent pericarditis: Results of the CORE (COlchicine for REcurrent pericarditis) trial. Archives of Internal Medicine, 165(17), 1987–1991. https://doi.org/10.1001/archinte.165.17.1987
  9. Imazio, M., Brucato, A., Cemin, R., Ferrua, S., Belli, R., Maestroni, S., Trinchero, R., Spodick, D. H., Adler, Y., & CORP (COlchicine for Recurrent Pericarditis) Investigators. (2011). Colchicine for recurrent pericarditis (CORP): A randomized trial. Annals of Internal Medicine, 155(7), 409–414. https://doi.org/10.7326/0003-4819-155-7-201110040-00359
  10. Imazio, M., Brucato, A., Cemin, R., Ferrua, S., Maggiolini, S., Beqaraj, F., Demarie, D., Forno, D., Ferro, S., Maestroni, S., Belli, R., Trinchero, R., Spodick, D. H., & Adler, Y. (2013). A Randomized Trial of Colchicine for Acute Pericarditis. New England Journal of Medicine, 369(16), 1522–1528. https://doi.org/10.1056/NEJMoa1208536
  11. Imazio, M., Pivetta, E., Restrepo, S. P., Sormani, P., Pedrotti, P., Quarta, G., Brucato, A., Bubbico, E., Corso, M. D., Milazzo, A., Quattrocchi, G., Andriani, M., Bodoni, L. L., Davini, O., Sironi, S., Giannattasio, C., Giustetto, C., Bogaert, J., Adler, Y., … Ferrari, G. M. D. (2020). Usefulness of Cardiac Magnetic Resonance for Recurrent Pericarditis. American Journal of Cardiology, 125(1), 146–151. https://doi.org/10.1016/j.amjcard.2019.09.026
  12. Imazio Massimo, Bobbio Marco, Cecchi Enrico, Demarie Daniela, Demichelis Brunella, Pomari Franco, Moratti Mauro, Gaschino Gianni, Giammaria Massimo, Ghisio Aldo, Belli Riccardo, & Trinchero Rita. (2005). Colchicine in Addition to Conventional Therapy for Acute Pericarditis. Circulation, 112(13), 2012–2016. https://doi.org/10.1161/CIRCULATIONAHA.105.542738
  13. Kauffman, C. A. (2017). Treatment of the Midwestern Endemic Mycoses, Blastomycosis and Histoplasmosis. Current Fungal Infection Reports, 11(3), 67–74. https://doi.org/10.1007/s12281-017-0281-x
  14. Lotrionte, M., Biondi-Zoccai, G., Imazio, M., Castagno, D., Moretti, C., Abbate, A., Agostoni, P., Brucato, A. L., Di Pasquale, P., Raatikka, M., Sangiorgi, G., Laudito, A., Sheiban, I., & Gaita, F. (2010). International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. American Heart Journal, 160(4), 662–670. https://doi.org/10.1016/j.ahj.2010.06.015
  15. Vecchié, A., Chiabrando, J. G., Dell, M. S., Bonaventura, A., Mauro, A. G., Wohlford, G., Van Tassell, B. W., Berrocal, D. H., Montecucco, F., Beutler, A., Paolini, J. F., Gal, T. S., & Abbate, A. (2020). Clinical Presentation and Outcomes of Acute Pericarditis in a Large Urban Hospital in the United States of America. Chest, S0012369220320584. https://doi.org/10.1016/j.chest.2020.07.039
  16. Wang, J. J., & Reimold, S. C. (2006). Chest Pain Resulting From Histoplasmosis Pericarditis: A Brief Report and Review of the Literature. Cardiology in Review, 14(5), 223–226. https://doi.org/10.1097/01.crd.0000204751.21288.20
  17. Wheat, L. J. (2006). Histoplasmosis: A review for clinicians from non-endemic areas. Mycoses, 49(4), 274–282. https://doi.org/10.1111/j.1439-0507.2006.01253.x
  18. Wheat, L. J., Freifeld, A. G., Kleiman, M. B., Baddley, J. W., McKinsey, D. S., Loyd, J. E., & Kauffman, C. A. (2007). Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 45(7), 807–825. https://doi.org/10.1086/521259

CardioNerds Case Reports: Recruitment Edition Series Production Team

86. Case Report: Histoplasmosis Pericarditis Complicated by Cardiac Tamponade – Georgetown University