Reversible Cardiomyopathy Associated with Multicentric Castleman Disease: Successful Treatment with Tocilizumab, an Anti-Interleukin 6 Receptor Antibody

Abstract

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by systemic lymphadenopathy and inflammatory symptoms that are associated with the overproduction of interleukin 6 (IL-6). Although several nonlymphoid organs can also be damaged in MCD, only a few cases with cardiac complications have been reported to date. We report a case of congestive heart failure in a female patient with MCD. On admission, her echocardiogram revealed a dilated and diffusely hypokinetic left ventricle. No stenosis was evident in the coronary angiogram. A histopathologic examination of a myocardial biopsy specimen showed mildly hypertrophic myocytes without infiltration of plasma cells or amyloid deposits. Repeated administration of an anti-IL-6 receptor antibody, tocilizumab (formerly known as MRA), gradually improved the ventricular wall motion over 6 months without any additional treatment for heart failure, suggesting the involvement of IL-6 in the pathogenesis of her cardiomyopathy. This report is the first of MCD complicated by heart failure treated successfully with tocilizumab. Administering tocilizumab in cases of MCD with unexplained cardiac dysfunction is worthwhile, because such a complication could be reversible.

Protein Engineering for Cardiovascular Therapeutics

“…In addition, IL-6 inhibition has been pursued via antagonism of its receptor (IL-6R or CD126) by an engineered, humanized monoclonal antibody, tocilizumab. Encouragingly, a human case report of tocilizumab administration resulting in successful improvement of cardiac dysfunction associated with multicentric Castleman disease by has been published 78 , and a clinical trial investigating the efficacy of tocilizumab in MI is ongoing 79 . Thus interleukin receptor antagonists may represent a promising path forward for protein engineering applied to cardiovascular therapy.…”

Antibody-Based Therapies in Multiple Myeloma

“…Tocilizumab specifically blocks IL-6 actions and ameliorates diseases associated with IL-6 overproduction [16]. For example, besides Castleman's disease and rheumatoid arthritis (RA), tocilizumab has been shown to be effective in patients with juvenile idiopathic arthritis and Crohn's disease [17, 18].…”

Critical appraisal of tocilizumab in the treatment of moderate to severe rheumatoid arthritis

“…IL-6 is thought to play a role in the pathogenesis of this disease, and the reversibility of cardiomyopathy following the use of tocilizumab in this case is intriguing. 40 IL-6 may have prognostic significance in predicting cardiovascular events in patients with angiographically proven and clinically stable CAD. 41 Additionally, IL-6 was found to be an independent and useful biomarker of atherosclerosis of 42 IL-6 was evaluated in patients undergoing coronary artery bypass grafting, and elevated preoperative IL-6 levels were predictors of both early graft occlusion and late cardiovascular events after surgery.…”