Rheumatology Advance Access originally published online on December 21, 2007
Rheumatology 2008 47(2):227-228; doi:10.1093/rheumatology/kem336
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Complete heart block after infliximab therapy
1Department of Medicine for the Elderly, 2Rheumatology Department, Llandudno General Hospital, Llandudno, Conwy and 3School of Medical Sciences, Bangor University, Brigantia, Penrallt Road, Bangor, UK
Correspondence to: S. Green, Rheumatology department, Llandudno General Hospital, Llandudno, Conwy, LL30 1LB. E-mail: sandraemgreen{at}hotmail.com
SIR, we report the case of a 78-yr-old woman who developed complete heart block (CHB) following her third dose of infliximab.
She was diagnosed with RA RF-positive at age 50 and was treated sequentially with sulphasalazine, azathioprine, methotrexate and leflunomide. Each DMARD was discontinued either due to side-effects or lack of efficacy. She was then treated with etanercept from summer 2003 to October 2004. This had to be discontinued due to hypertension and headaches (which improved with stopping etanercept). Subsequently, she was treated for 12 months with adalimumab, which was ineffective (discontinued in December 2005).
Her RA continued to be active on prednisolone 10 mg once daily and in August 2006 she started infliximab (3 mg/kg) and methotrexate (7.5 mg once weekly). Her other medical problems were hypertension, osteoporosis, indigestion and nausea for which she was taking lisinopril, amlodipine, residronate, omeprazole and metoclopramide. There was no history of ischaemic heart disease, but a routine ECG performed in April 2006 showed first-degree heart block, at a rate of 70 beats/min.
Patients having infliximab in our unit are admitted overnight for the first three infusions. The first infusion was uneventful at week 0. Following the second infusion 2 weeks later, she then gave a history of dry cough for 3–4 months. A chest X-ray was performed, which showed an increased number of nodules (which were of varying sizes) in comparison to a chest X-ray taken 2 months previously, which had been initially reported as ‘normal’ but on review showed a small number of opacities. A high-resolution computed tomography (HRCT) chest scan was then performed, which confirmed the presence of these opacities, but excluded hilar lymphadenopathy or interstitial lung disease. The patient refused a lung biopsy to confirm that these were rheumatoid nodules (RhN). However, a multidisciplinary meeting involving the rheumatologist, respiratory physician and radiologist concluded that these nodules were most likely rheumatoid in nature taking into account the rapidity with which the opacities increased, and the clinical condition of the patient.
A third dose of infliximab was given at 6 weeks. Routine observations carried out immediately post-infusion picked up a pulse rate of 42 beats/min. She continued to remain bradycardic, and by 18 h post-infusion, her pulse rate had dropped to 25 beats/min. She maintained an adequate blood pressure with an average of 180/90 mmHg. She had no cardiorespiratory symptoms or signs of heart failure. A 12 lead ECG confirmed the bradycardia at a rate of 35–40 beats/min and CHB. Urea and electrolytes, thyroid function tests, cardiac enzymes including troponins were all normal. After cardiology review, she was discharged home, and a permanent pacemaker was inserted at a later date. Review of her RA at 3 months did not show an improvement in disease activity score (DAS)-28 and no further infliximab was given.
Bradycardia [1] and heart failure are recognized side-effects of infliximab, and there are two case reports of patients developing second-degree atrioventricular block during the infliximab infusion [2]. To our knowledge there are no reports in the medical literature of CHB following infliximab infusion or treatment with any other anti-TNF.
Conduction disturbances, including CHB, are well recognized within the RA population [3]. Cardiac RhN are reported to be present in between 1% and 3% of RA patients [4–6]. Pizzarello and Goldberg [3] suggest that RhN could cause conduction disturbances at the sino-atrial or atrioventricular (AV) nodes or His-Purkinje system. The conduction tissue could be compressed by RhN, or directly invaded, or be compromised by impaired blood supply.
In this patient, it was noticed that she had increased pulmonary nodulosis after commencing infliximab. It was at this stage that she developed complete heart block. It is probable that the CHB was due to a RhN at the AV node. Our patient did not have any subcutaneous nodules.
There are case reports of accelerated nodulosis (subcutaneous and pulmonary) following etanercept [7, 8] and infliximab therapy [9]. The authors postulate that this could have been due to autoimmune phenomena occurring with anti-TNF therapy or due to the natural history of RA. Other authors hypothesize that the mechanisms of nodulosis are largely TNF-
-independent [10].
Given that the onset of CHB in this patient was immediately following her third infliximab infusion, it is likely that infliximab played a role in the development of CHB in this case, probably by exacerbating a nodule at the AV node. Unfortunately, we were unable to prove the presence of nodules in this patient's heart as we were unable to obtain a magnetic resonance imaging scan prior to pacemaker insertion. HRCT scanning of our patient is not justified on clinical grounds.
We recommend that all patients have an ECG performed prior to anti-TNF to exclude cardiac conduction abnormalities. It would seem prudent to be vigilant in patients with pre-existing cardiac conduction problems or nodulosis elsewhere if the decision to treat with infliximab is made.
Disclosure statement: The authors have declared no conflicts of interest.
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