Lupus (2014) 23, 711–713 http://lup.sagepub.com
CASE REPORT
A case of progressive multifocal leukoencephalopathy in a lupus patient treated with belimumab CA Fredericks1, KA Kvam1, J Bear1, GS Crabtree2 and SA Josephson1 1
University of California San Francisco, San Francisco, USA; and 2Thomas Jefferson University, Philadelphia, USA
Belimumab is a monoclonal antibody against soluble B-lymphocyte stimulator, an essential growth factor for B-cell maturation and activation, which was approved by the US FDA in 2011 for patients with active autoantibody-positive systemic lupus erythematosus (SLE) who have failed standard treatment. Here we present the case of a 40-year-old woman with SLE diagnosed with progressive multifocal leukoencephalopathy (PML) on belimumab. After a total of 10 infusions of belimumab, from August 2012 through April 2013, in April 2013 she developed progressive neurologic decline with episodic dystonia and autonomic symptoms. Her imaging showed multifocal, confluent regions of T2 hyperintensity in the white matter bilaterally, and CSF JCV PCR returned positive. Based on the patient’s clinically mild SLE and the timing of symptom onset, belimumab likely played a key role in the development of PML. Trials of belimumab for other autoimmune diseases are ongoing; as applications for this novel drug broaden, careful monitoring for this potentially fatal adverse effect is warranted. Lupus (2014) 23, 711–713. Key words: Systemic lupus erythematosus; PML; neuropsychiatric lupus
Belimumab is a fully humanized monoclonal antibody against soluble B-lymphocyte stimulator (BLyS), an essential growth factor for B-cell maturation and activation.1 B-cell activation plays a key role in the pathophysiology of systemic lupus erythematosus (SLE), leading to increased formation of antibody-producing plasma cells, increased secretion of pro-inflammatory cytokines, and increased availability of B cells to present autoantigens to T cells. BLyS promotes B-cell activation and has been found to be elevated in the serum of at least 50% of patients with SLE.2 Belimumab was approved by the Unites States Food and Drug Administration in March 2011 for patients with active autoantibody-positive SLE who have failed standard treatment. We diagnosed progressive multifocal leukoencephalopathy (PML) in a 40-year-old woman with SLE who was on belimumab. She had received a Correspondence to: CA Fredericks, University of California, San Francisco. 505 Parnassus Ave, Box 0114, San Francisco, CA 94143. Email: [email protected] Received 4 November 2013; accepted 23 January 2014
total of 10 monthly belimumab infusions from August 2012 through April 2013, during which time she was also taking mycophenolate mofetil and low-dose prednisone. In April 2013, she developed progressive neurologic decline with prominent bulbar weakness and episodic dystonic posturing, tachycardia, and hypertension. In May 2013, she was hospitalized at another institution and diagnosed with central nervous system (CNS) lupus based in part on magnetic resonance imaging (MRI) of the brain (Figure 1). She was treated with high-dose steroids and two cycles of cyclosphosphamide but continued to decline. On admission to our hospital in August 2013, repeat MRI of the brain showed increased multifocal, confluent areas of T2 hyperintensity in the bilateral white matter (Figure 1). Serum testing showed normal levels of CD3 and CD8 cells but undetectable CD19 (
CASE REPORT
A case of progressive multifocal leukoencephalopathy in a lupus patient treated with belimumab CA Fredericks1, KA Kvam1, J Bear1, GS Crabtree2 and SA Josephson1 1
University of California San Francisco, San Francisco, USA; and 2Thomas Jefferson University, Philadelphia, USA
Belimumab is a monoclonal antibody against soluble B-lymphocyte stimulator, an essential growth factor for B-cell maturation and activation, which was approved by the US FDA in 2011 for patients with active autoantibody-positive systemic lupus erythematosus (SLE) who have failed standard treatment. Here we present the case of a 40-year-old woman with SLE diagnosed with progressive multifocal leukoencephalopathy (PML) on belimumab. After a total of 10 infusions of belimumab, from August 2012 through April 2013, in April 2013 she developed progressive neurologic decline with episodic dystonia and autonomic symptoms. Her imaging showed multifocal, confluent regions of T2 hyperintensity in the white matter bilaterally, and CSF JCV PCR returned positive. Based on the patient’s clinically mild SLE and the timing of symptom onset, belimumab likely played a key role in the development of PML. Trials of belimumab for other autoimmune diseases are ongoing; as applications for this novel drug broaden, careful monitoring for this potentially fatal adverse effect is warranted. Lupus (2014) 23, 711–713. Key words: Systemic lupus erythematosus; PML; neuropsychiatric lupus
Belimumab is a fully humanized monoclonal antibody against soluble B-lymphocyte stimulator (BLyS), an essential growth factor for B-cell maturation and activation.1 B-cell activation plays a key role in the pathophysiology of systemic lupus erythematosus (SLE), leading to increased formation of antibody-producing plasma cells, increased secretion of pro-inflammatory cytokines, and increased availability of B cells to present autoantigens to T cells. BLyS promotes B-cell activation and has been found to be elevated in the serum of at least 50% of patients with SLE.2 Belimumab was approved by the Unites States Food and Drug Administration in March 2011 for patients with active autoantibody-positive SLE who have failed standard treatment. We diagnosed progressive multifocal leukoencephalopathy (PML) in a 40-year-old woman with SLE who was on belimumab. She had received a Correspondence to: CA Fredericks, University of California, San Francisco. 505 Parnassus Ave, Box 0114, San Francisco, CA 94143. Email: [email protected] Received 4 November 2013; accepted 23 January 2014
total of 10 monthly belimumab infusions from August 2012 through April 2013, during which time she was also taking mycophenolate mofetil and low-dose prednisone. In April 2013, she developed progressive neurologic decline with prominent bulbar weakness and episodic dystonic posturing, tachycardia, and hypertension. In May 2013, she was hospitalized at another institution and diagnosed with central nervous system (CNS) lupus based in part on magnetic resonance imaging (MRI) of the brain (Figure 1). She was treated with high-dose steroids and two cycles of cyclosphosphamide but continued to decline. On admission to our hospital in August 2013, repeat MRI of the brain showed increased multifocal, confluent areas of T2 hyperintensity in the bilateral white matter (Figure 1). Serum testing showed normal levels of CD3 and CD8 cells but undetectable CD19 (
