Recurrent Pericarditis: Is Immunotherapy the Answer? Shir Azrielant MD1,3, Yehuda Shoenfeld MD, FRCP, MACR1,3,4 and Yehuda Adler MD, MHA2,3
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EDITORIALS ,0$-ǯ92/20ǯ0$5&+2018 Recurrent Pericarditis: Is Immunotherapy the Answer? Shir Azrielant MD1,3, Yehuda Shoenfeld MD, FRCP, MACR1,3,4 and Yehuda Adler MD, MHA2,3 1Zabludowicz Center for Autoimmune Diseases and 2Department of Hospital Management, Sheba Medical Center, Tel Hashomer, Israel 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 4Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases INTERLEUKIN-1 ANTAGONISTS site reaction in up to 44% of patients [13]. KEY WORDS: recurrent pericarditis, Interleukin-1 (IL-1) is a family of cyto- Other rare adverse effects include transami- immunotherapy, interleukin 1 (IL1), kines involved in both acute and chronic nases elevation [9,10], herpes zoster, and intravenous immunoglobulin (IVIG) inflammation. IL-1β was found to be asso- optic neuropathy [10]. IMAJ 2018; 20: 190–191 ciated with autoimmune conditions, and is therefore used as a therapeutic target. IL-1 INTRAVENOUS IMMUNOGLOBULINS antagonists, such as anakinra, are used to Intravenous immunoglobulins (IVIG) are treat autoimmune and autoinflammatory comprised of pooled immunoglobulin G ericarditis is considered recurrent when conditions such as familial Mediterranean (IgG) antibodies from serum of thousands P reappearance of symptoms occurs after fever [7]. of donors. Although initially intended for resolution of the initial acute attack, usually Treatment with anakinra was previously treatment of immunocompromised patients, after 4 to 6 weeks. This complication is seen tested in relatively small samples, but the discovery of its immunomodulatory effects in up to 32% of acute pericarditis cases, results seemed promising. The treatment led to its use in different autoimmune and and may increase up to 50% in untreated resulted in complete remission in cortico- autoinflammatory conditions [15]. cases [1]. steroid-dependent patients and enabled In recent years, evidence has accumu- The pathogenesis and specific etiologies discontinuation of corticosteroid treatment lated regarding the beneficial role of IVIG in of recurrent pericarditis are still largely [8]. Another study reached similar conclu- the treatment of refractory recurrent peri- unknown, and therefore it is also referred sions, with complete and relatively fast carditis. Early evidence from case reports to as idiopathic recurrent pericarditis. remission (within a few days) [9]. An inter- show efficacy and safety of high-dose Autoimmunity, however, seems to play a ventional double-blind placebo-controlled IVIG treatment for recurrent pericarditis crucial role. The autoimmune and autoin- trial from Italy demonstrated significant attributed to different etiologies [16,17]. A flammatory nature of the disease can be reduction in pericarditis recurrence in small scale retrospective trial conducted in shown by the prevalence of autoantibodies colchicine-resistant and corticosteroid- patients with no documented autoimmune in recurrent pericarditis patients [2] and in dependent patients [10]. Similar results diseases concluded that IVIG was effective the effectiveness of immunosuppressant were also seen in case reports, in both chil- in recurrent pericarditis treatment, with therapies in the disease [1]. dren [11] and adults [12]. no major side effects documented [18]. A The management of recurrent pericardi- A review conducted in 2016 by Lazaros recent review of all published cases reported tis is challenging. The efficacy of colchicine et al. [13] reported that C-reactive protein 73.3% of patients treated with one cycle of [3,4] and non-steroidal anti-inflammatory (CRP) levels were normalized within an IVIG (400–500 mg/kg/day for 5 consecutive drugs (NSAID) [1] in prevention of recur- average of 7.1 days, and corticosteroids days) did not have recurrent episodes, and rence is well-established, as are certain were discontinued within 62 days. only 16.6% still needed corticosteroid treat- corticosteroid regimens in refractory cases It is important to note that discontinu- ment at the end of the follow-up period [19]. [5]. In the case of corticosteroids, however, ation of anakinra leads to relapses in many The recommended dose for IVIG is aside from their well-known adverse effects cases, and therefore it seems that anakinra 400–500 mg/kg daily for 5 days, with no on other organ systems, they have also been should be used as a long-term treatment tapering needed [14]. The adverse effects associated with an increased recurrence of [8,9]. The length of the treatment protocol that are described include headaches, pericarditis, making them a double-edged is still unknown. which were documented in 3% of subjects sword [6]. Certain immunosuppressive The recommended dose is 1–2 mg/kg [19], as well as flushing, chills, tachycardia, therapies, such as azathioprine, have also daily, up to 100 mg/daily in adults, for nausea, fatigue, and hypotension [20]. been previously suggested [1]. several months. It is not yet determined The major disadvantage of IL-1 antago- In this article, we will discuss new emerg- whether tapering down is needed [14]. nists and IVIG therapies is their high cost ing therapies for recurrent pericarditis. Adverse effects described are injection and their methods of administration. 190 ,0$-ǯ92/20ǯ0$5&+2018 EDITORIALS Anakinra is injected subcutaneously, while Heart J 2015; 36 (42): 2921-64. 11. Picco P, Brisca G, Traverso F, et al. Successful IVIG is infused, usually in a hospital set- 2. Imazio M, Brucato A, Doria A, et al. Antinuclear treatment of idiopathic recurrent pericarditis in children with interleukin‐1β receptor antagonist ting. Currently, these agents serve as a antibodies in recurrent idiopathic pericarditis: prevalence and clinical significance. Int J Cardiol (anakinra): an unrecognized autoinflammatory fourth-line of treatment, after different 2009; 136: 289-93. disease? Arthritis Rheum 2009; 60: 264-8. combinations of aspirin, NSAID, and col- 3. Adler Y, Finkelstein Y, Guindo J, et al. Colchicine 12. Scott IC, Hajela V, Hawkins PN, et al. A case series and systematic literature review of anakinra chicine [14]. This recommendation is clas- treatment for recurrent pericarditis. Circulation 1998; 97: 2183-5. and immunosuppression in idiopathic recurrent sified as class IIb [1]. pericarditis. J Cardiol Cases 2011; 4: e93-7. 4. Imazio M, Bobbio M, Cecchi E, et al. 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