Treatment
Acute primary pericarditis and recurrence are treated with a combination of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin and colchicine (Figure 1) (1). Restriction of physical activity is recommended (1). Colchicine as an adjunct to NSAIDs or aspirin produces more rapid resolution of symptoms and reduced risk of repeat hospitalisation and recurrence (1). Colchicine as maintenance treatment can also prevent recurrence in some patients.
In cases of acute primary pericarditis or a first recurrence, corticosteroids should only be used in patients with a contraindication for colchicine and NSAIDs or aspirin (1). The ESC guidelines recommend the use of corticosteroids such as prednisolone for subsequent recurrences (1). Tapering should take place over several months and only when the patient remains in remission during tapering (1). Nevertheless, many patients experience recurrence when the prednisolone dose is tapered to 10–15 mg daily (4). Long-term use of corticosteroids often leads to serious adverse reactions. Therefore, HbA1c, lipid profile, blood pressure and bone density must be measured, and prophylactic treatment given to prevent gastric ulcer and osteoporosis. Corticosteroids have also been associated with a dose-related risk of recurrence (5, 6). In the event of recurrence during tapering, consideration should be given to initiating treatment with immunomodulating drugs such as anakinra, azathioprine or intravenous immunoglobulins (IVIG) (1).
Following new understanding about the pathogenesis, there is increasing evidence for the use of interleukin-1 inhibitors in the treatment of recurrent pericarditis (15). The most widely used drug is anakinra (interleukin-1 receptor antagonist) as a daily subcutaneous injection (16). Anakinra has a half-life of approximately four to six hours, and in certain serious cases it may be appropriate to give a full dose two to three times daily at treatment initiation. When concomitant treatment is administered with prednisolone, NSAIDs or aspirin and colchicine, these can be tapered, one at a time, once the patient is in remission (1). Monotherapy with anakinra is adequate for most patients after eight to ten weeks (16). An attempt to taper anakinra can be made after three to six months, for example with the reduction of one daily dose per week every two or three weeks over a period of at least three months (16). Consideration can be given to attempting discontinuation, but the duration of treatment and tapering may have an impact on the rate of recurrence (16). Recurrence is experienced by 33–71 % of patients after tapering, and consequently anakinra (one to three injections per week) often needs to be administered for several years (4).
Use of interleukin-1 inhibitors early in the disease course and before initiating treatment with corticosteroids can be considered if there are signs of pericardial constriction, widespread inflammation on CMR, subacute course and high levels of CRP, ferritin or soluble interleukin-2 receptor (11, 16). Remission is usually achieved after a few days of treatment with anakinra. A lack of response should lead to further workup to investigate differential diagnoses. Transient cutaneous reactions at the injection site are common, while other adverse reactions, such as impact on liver function tests and leukopenia, are rare (16). It is important that the patient is trained in the use of anakinra and properly informed about the management of adverse reactions to prevent early discontinuation of treatment.
In the event of adverse reactions with anakinra, canakinumab, an anti-interleukin-1β antibody, can be tried. However, making such a switch requires that anakinra has been effective since canakinumab has the same mechanism of action (17). Canakinumab is administered every four to eight weeks and causes considerably fewer cutaneous reactions than anakinra, although the price is much higher.
Before initiating treatment with interleukin-1 inhibitors, pregnancy, tuberculosis, HIV and hepatitis B and C must be ruled out. Liver function tests and blood count must be checked before the start of treatment and after one month (16), and thereafter every three months during administration of the drug. Vaccination status should be updated before starting treatment, although patients can receive all non-live vaccines during treatment.
Azathioprine and intravenous immunoglobulins are possible alternatives to anakinra in cases of recurrent pericarditis, although the evidence for treatment with these drugs is sparse. Interleukin-6 inhibition, for example with tocilizumab, can be considered in the event of an incomplete response to anakinra with considerable elevation of CRP and interleukin-6 levels. However, there is little evidence for treatment with interleukin-6 inhibitors, and only for pericarditis associated with rheumatic diseases (18).
Pericardiectomy may be appropriate for individual patients with irreversible pericardial constriction when laboratory tests and imaging investigations no longer show signs of inflammation (19). Before pericardiectomy is considered, simultaneous right and left heart catheterisation should be performed to evaluate haemodynamic impact. Pericardiectomy is advanced surgery, but has potentially very good results at highly specialised centres (19).