Successful etanercept treatment of constrictive pericarditis complicating rheumatoid arthritis

E. Aslangul, S. Perrot, E. Durand1, E. Mousseaux2, C. Le Jeunne and L. Capron3

Service de Médecine Interne, Hotel Dieu, 1 Service de Cardiologie, 2 Service de Radiologie vasculaire, and 3 Service de Médecine Interne, Hopital Européen Georges Pompidou, Paris, France

Correspondence to: S. Perrot, Service de Médecine Interne, Université Paris 5, René Descartes, Hotel Dieu, Place du Parvis Notre Dame, 75003 Paris, France. E-mail: serge.perrot{at}htd.aphp.fr

SIR, Effusive-constrictive pericarditis is a rare complication of pericarditis. Indeed, Sagrista-Sauleda et al. [1] observed only 15 cases in a prospective series of 1184 patients with pericarditis collected over 15 yr. After observing one case of rheumatoid arthritis with relapsing pericarditis eventually leading to severe pericardial constriction, despite intensive use of common disease-modifying drugs, we tested etanercept, an antagonist of tumour necrosis factor alpha (TNF-{alpha}), in a last attempt to avoid surgery.

A 36-yr-old woman was admitted to the cardiothoracic surgery department of our hospital in September 2003 because of pericarditis with cardiac tamponade. She had been treated for nodular and erosive rheumatoid arthritis for the past 5 yr with 10 mg/day prednisolone and 2 g/day salazopyrin. She also had chronic quiescent hepatitis C infection. She was not a drug addict and not a smoker. No other extra-articular involvement related to rheumatoid arthritis was found. Pericardial drainage yielded 1100 ml of fluid containing inflammatory cells (neutrophils and macrophages) but no bacteria, especially no mycobacteria after culture. The concentration of blood rheumatoid factor was 335 IU/ml (normally <15 IU/ml), ESR was 80 mm in the first hour and CRP was 70 mg/l. Rheumatoid pericarditis was diagnosed and immunosuppressive treatment was intensified: one intravenous bolus (250 mg) of methylprednisolone, followed by 10 mg/day prednisolone and 50 mg/day azathioprine. The patient rapidly improved and was discharged from hospital after 1 week.

Three months later, she presented again with pericarditis and tamponade. She underwent a second pericardiocentesis with drainage of 1050 ml. Treatment was strengthened with 100 mg/day azathioprine and 1 mg/kg/day prednisolone. This resulted in complete resolution of the pericardial effusion within 1 week. Prednisolone was rapidly tapered, but a third episode of pericardial effusion recurred 1 month later, when the dose had reached 15 mg/day. This time, she presented progressive right heart failure and was diagnosed with constrictive pericarditis, on the basis of echocardiography showing an 8 mm-thick posterior pericardium with moderate pericardial effusion. Doppler examination revealed a dip-plateau aspect of the pulmonary regurgitation flow. Cardiac magnetic resonance imaging (MRI) revealed inflammation of the pericardium with circumferential pericardial effusion, increased thickness and high signal intensity of both visceral and parietal layers of the pericardium due to enhancement 10 min after gadolinium injection (Fig. 1). We started anti-inflammatory therapy with three intravenous boluses (500 mg each) of methylprednisolone. No improvement was noted after 1 week. In an attempt to avoid surgical epicardiectomy, we decided to try antagonization of TNF-{alpha} with subcutaneous etanercept, 25 mg twice weekly. After 1 week, oedema and ascites had completely disappeared. Cardiac Doppler revealed that the dip-plateau aspect had resolved. Pericardial extravasation had decreased from 14 to 5 mm. The patient was discharged from hospital 10 days after the start of anti-TNF-{alpha} therapy. Six months later, no right ventricular signs or oedema have recurred. The MRI revealed that the pericardium was still abnormally thick, but it was now mobile throughout the cardiac cycle and did not enhance after contrast administration (Fig. 1).



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FIG. 1. Four chamber views of the heart in a cine gradient-echo technique (A and B) and small axis views in an inversion recovery gradient echo-technique 10 min after contrast administration (0.2 mmol/kg body weight Gd-DTPA) (C and D), before (A and C) and after three months of anti-TNF treatment (B and D).

Note the pericardial effusion (arrow in A and C), and the high signal intensity of both visceral and parietal layers of the pericardium due to the enhancement (open arrow head in C, before anti-TNF treatment), which are signs of acute inflammation. The increased thickness of the pericardium was still observed (filled arrow heads in B and D) after treatment but this pericardium was mobile using cine dysplay and not enhanced using the same inversion recovery gradient echo-technique after contrast administration.

 
Pericarditis occurs in 30–50% of rheumatoid arthritis patients, but only 1–3% were symptomatic in a set of patients assessed before 1990 [2]. Analysis of pericardial fluid commonly reveals inflammation with neutrophils [2]. Corticotherapy is usually curative but does not prevent recurrences or complications, and disease-modifying drugs are not efficient in rheumatoid pericarditis [2]. Complications of pericarditis, such as cardiac tamponade or constriction, are very rare in rheumatoid arthritis: 200 cases have been reported in the literature [3]. In rheumatoid pericardial constriction, steroids are totally inefficient and epicardiectomy is the only effective treatment described so far [3].

In our case, the first two episodes of pericarditis were complicated by cardiac tamponade. Surgical pericardial drainage preceded intensification of steroid therapy, which was successful on both occasions, with complete regression of clinical and echocardiographic abnormalities within 1 week. During the third episode within 4 months, constrictive pericarditis was diagnosed using echocardiography and Doppler, which showed signs typical enough to avoid cardiac catheterization [4]. Corticosteroid therapy, the aim of which was to reduce pericardial inflammation and effusion, was totally inefficient despite very high doses of methylprednisolone [5]. We decided to try anti-TNF-{alpha} therapy because the patient was quite reluctant to undergo a third surgical intervention and because anti-TNF therapy is the reference treatment for rheumatoid arthritis [6]. Dramatic clinical echocardiographic improvement followed rapidly: the dip-plateau disappeared within 1 week, and pericardial effusion completely resolved within 1 month. As pericardial inflammation involved the entire circumference, as shown by MRI, it is likely that the fibrosis was not yet fixed [7].

This report strongly suggests that anti-TNF-{alpha} therapy is effective in cases of constrictive pericarditis complicating rheumatoid arthritis, with established resistance to more conventional disease-modifying drugs. We conclude that etanercept therapy seems to be highly effective in inflammatory and constrictive pericarditis complicating rheumatoid arthritis, and should be considered as an alternative to surgery.

References

  1. Sagrista-Sauleda J, Angel J, Sanchez A et al. Effusive-constrictive pericarditis. N Engl J Med 2003;350:469–75.[CrossRef][ISI]
  2. Hara KL, Ballard DJ, Ilstrup DM et al. Rheumatoid pericarditis. Medicine 1990;69:81–91.[ISI][Medline]
  3. Escalante A, Kaufman RL, Quismorio FP et al. Cardiac compression in rheumatoid pericarditis. Arthritis Rheum 1990;20:148–63.[CrossRef]
  4. Cohen A, Guyon P, Chauvel C et al. Relations between Doppler tracings of pulmonary regurgitation and invasive hemodynamics in acute right ventricular infarction complicating inferior wall left ventricular infarction. Am J Cardiol 1995;75:425–30.[CrossRef][ISI][Medline]
  5. McRorie ER, Errington ML, Luqmani RA. Rheumatoid constrictive pericarditis. Br J Rheumatol 1997;36:100–3.[CrossRef][ISI][Medline]
  6. Weinblatt ME, Kremer JM, Bankhurst AD et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253–9.[Abstract/Free Full Text]
  7. Klein C, Graf K, Fleck E et al. Acute fibrinous pericarditis assessed with magnetic resonance imaging. Circulation 2003;107:e82.[Free Full Text]
Accepted 14 July 2005





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