Diagnosis and Treatment

Understanding The Current Standard of Care

Management of recurrent pericarditis is a particular clinical challenge. There are currently no treatment guidelines issued in the US for the management of pericarditis, although some experts have developed their own approach based on guidelines from the European Society of Cardiology (ESC).1-3

Standard therapies may address the symptoms of recurrent pericarditis, but not the underlying IL-1 -mediated pathophysiology .1,4

Diagnosing Pericarditis

Diagnosis of acute pericarditis requires 2 of these 4 pericarditis
diagnostic characteristics1:

  • Pleuritic chest pain that is worse with inspiration and when supine

  • Pericardial friction rub as heard through a stethoscope) 

  • Characteristic ST-segment elevation and PR depression on electrocardiogram (ECG)

  • Pericardial effusion that is more than trivial  
Diagnosis of subsequent recurrences of pericarditis in patients with an established history of recurrent pericarditis is challenging because these patients5:
  • Often have chest pain regardless of their recurrence status

  • Lack enough clinical evidence to meet the diagnostic criteria of pericarditis because patients are on multiple anti-inflammatory medications


In addition to the established diagnostic criteria, these additional tests are suggested2:

  • Serologic tests
    • C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) to confirm inflammation2
  • Imaging tests
    • Computed tomography (CT) or cardiac magnetic resonance (CMR) to help assess the risk of developing complications that include pericardial tamponade or constrictive pericarditis2
    • Pericardial delayed hyperenhancement (DHE) on CMR images to help improve the ability to diagnose ongoing recurrences and help provide insights into the duration and expected response to therapy in patients with an established history of recurrent pericarditis5,6

A diagnosis of recurrent pericarditis follows the same
criteria as acute pericarditis, plus history of a previous
episode at least 4 to 6 weeks prior.2

Treatment Approaches

In the US, treatment of recurrent pericarditis generally involves the use of therapies that are not FDA-approved for the treatment or prevention of recurrent pericarditis. US experts have drawn from the ESC guidelines to develop a stepwise approach that depends on phases of recurrence.1,3

Suggested treatment approach for complicated pericarditis1,3,7

Therapy typically starts with aspirin or nonsteroidal anti-inflammatory drugs
(NSAIDs) with or without colchicine. Physicians may also add low-dose
corticosteroids and other agents as needed. Restrictions on exercise may
also be advised.4


  • NSAIDs (weeks)
  • Colchicine (3 months)

First recurrence

Aspirin or NSAIDs (weeks)
+ Colchicine (>6 months)

Multiple recurrences

Aspirin or NSAIDs
+ Colchicine
+ Low-dose corticosteroids for
   >6 months (taper as tolerated)

Consider use of steroid-sparing immunomodulators

Colchicine resistant or steroid dependent*

+ Colchicine
+ Corticosteroids
+ Steroid-sparing agent (AZA or IVIG) for
   >6-12 months (taper as tolerated)

Consider pericardiectomy
(warrants further study)

*Unable to withdraw corticosteroids without a relapse.


  • Intensify medical therapy
  • Pericardiectomy if all other options are exhausted

Targeting autoinflammation

Most treatments currently being used to manage recurrent pericarditis symptoms do not target the specific mechanism of autoinflammation primarily driven by IL-1? and IL-1β.1,8,9


  • NSAIDs and corticosteroids nonspecifically reduce inflammation
    • For some patients, it has been shown that the recurrence rate is lower following the first episode of acute idiopathic pericarditis when no corticosteroids are administered10
  • Colchicine blocks tubulin polymerization, thereby nonspecifically disrupting several functions in immune cells (especially granulocytes)7
    • Colchicine administration does not seem to have any relevant influence on the recurrence rate or on the severity of clinical manifestations10
  • Immunomodulators are potent steroid-sparing agents that broadly suppress or modulate the immune system11,12


Possible side effects of treatment approaches

While none of the following therapies for pericarditis are FDA approved for the condition, physicians have achieved some success with these treatments. There are limited studies assessing their utility in recurrent pericarditis, and all carry the potential risk of side effects that can complicate management.7 Below is a partial list of possible side effects based on reviews from experts in the field of pericarditis.


  • Gastrointestinal (GI) disturbances7
  • Potential for serious GI bleeding13
  • Heart attack14
  • Stroke14


  • GI disturbances, particularly diarrhea


  • Mood change
  • Mental health problems
  • Fatty deposits in the face
  • Osteoporosis
  • Previous use is reported to be associated
    with an increased risk of recurrence


  • Transient hepatotoxicity
  • Leukopenia
  • Transient gastrointestinal symptoms
  • Liver toxicity and myelosuppression


  • Headache
  • Possible safety concerns associated with
    infusing a derivative of donor plasma

The last treatment option

The lack of an appropriate therapy often results in an increase in both the frequency
and rate of recurrences.15 In some patients, it can also increase the risk of developing
chronic constrictive pericarditis requiring pericardiectomy. Surgical removal of the
pericardium has been associated with postoperative mortality rates of 6% to 12%.3

Other possible approaches

In addition to the treatments listed above, alternative, targeted immunomodulating approaches are being assessed that block IL-1 
signaling are also available.4,16 

Recombinant IL-1
receptor antagonist

Directly blocks the IL-1 receptor,
thereby antagonizing the action
of both IL-1α and IL-1β17

Monoclonal antibody

Specifically binds and neutralizes
IL-1β with no effect on IL-1α18

IL-1 decoy
receptor trap

Specifically binds and neutralizes
(traps) both IL-1α and IL-1β19


There are currently no treament guidelines issued in the US for the management of recurrent pericarditis.4

Standard therapies may address the symptoms of recurrent pericarditis, but not the underlying IL-1-mediated pathophysiology.1,4

Alternative immunomodulating approaches are being assessed for targeting and blocking IL-1 signaling are also available.4,16

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  2. Chiabrando JG, Bonaventura A, Vecchie A, et al. Management of acute and recurrent pericarditis. J Am Coll Cardiol. 2020;75(1):76-92.
  3. Adler Y, Charron P, Imazio M, et al. 2015 ESC guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2015;36(42):2921-2964.
  4. Klein, AL, Imazio M, Brucato A, et al. RHAPSODY: rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β trap, in patients with recurrent pericaditis. Am Heart J  2020;228:81-90.
  5. Kumar A, Sato K, Verma BR, et al. Quantitative assessment of pericardial delayed hyperenhancement helps identify patients with ongoing recurrences of pericarditis. Open Heart. 2018;5:e000944.
  6. Kumar A, Sato K, Yzeiraj E, et al. Quantitative pericardial delayed hyperenhancement informs clinical course in recurrent pericarditis. JACC Cardiovasc Imaging. 2017;10(11):1337-1346.
  7. Imazio M, Lazaros G, Brucato A, Gaita F. Recurrent pericarditis: new and emerging therapeutic options. Nat Rev Cardiol. 2016;13(3):99-105.
  8. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633-652.
  9. Brucato A, Imazio M, Cremer PC, et al. Recurrent pericarditis: still idiopathic? The pros and cons of a well-honoured term. Intern Emerg Med. 2018;13(6):839-844.
  10. Sambola A, Roca Luque I, Mercé J, et al. Colchicine administered in the first episode of acute idiopathic pericarditis: a randomized multicenter open-label study. Rev Esp Cardiol (Engl Ed). 2019;72(9):709-716.
  11. Maltzman JS, Koretzky GA. Azathioprine: old drug, new actions. J Clin Invest. 2003;111(8): 122-124.
  12. Gilardin L, Bayry J, Kaver SV. Intravenous immunoglobulin as clinical immune-modulating therapy. CMAJ. 2015;187(4):257-264.
  13. Buckley LF, Viscusi MM, Van Tassel BW, Abbate A. Interleukin-1 blockade for the treatment of pericarditis. Eur Heart J Cardiovasc Pharmacother. 2018;4(1):46-53.
  14. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. US Food and Drug Administration. July 9, 2015. Updated February 26, 2018. Accessed April 14, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory
  15. Data on file #8. Kiniksa Pharmaceuticals (UK), Ltd.
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  17. Kineret. Package insert. Swedish Orphan Biovitrum AB; 2018.
  18. Ilaris. Package insert. Novartis Pharmaceuticals Corporation; 2016.
  19. ARCALYST. Package insert. Kiniksa Pharmaceuticals (UK), Ltd; 2021.