Infectious CNS disease as a differential diagnosis in systemic rheumatic diseases: three case reports and a review of the literature

Warnatz, Klaus; Peter, Hans‐Hartmut; Schumacher, M.; Wiese, Lothar; Prasse, Antje; Petschner, F; Vaith, P; Volk, Bruno W.; Weiner, Stefan M.

doi:10.1136/ard.62.1.50

Cited by 95 publications

(54 citation statements)

References 59 publications

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“…60 There has been one documented case of progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematous receiving leflunomide. 61 This case was complicated by the fact that the patient had already been on several immunosuppressive drugs including prednisone, azathioprine, chloroquine, danazol, cyclosporine A, and finally, methotrexate. No data exists linking teriflunomide use with progressive multifocal leukoencephalopathy.…”

Section: Safety and Tolerability Of Teriflunomidementioning

confidence: 99%

Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis

Nwankwo¹,

Allington²,

Rivey³

2012

DNND

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Treatment for multiple sclerosis (MS), a chronic disease of the central nervous system, has historically relied exclusively on the use of injectable therapies. As the disease requires lifelong therapy, the development of oral therapies that are safe and effective would provide a more convenient dosage form that may improve patient compliance. One oral medication (fingolimod) was recently approved for treatment of MS. Teriflunomide, an immunomodulator, is one of four oral therapies currently undergoing Phase III trials. Teriflunomide exerts its clinical effects via selective inhibition of de novo pyrimidine synthesis, primarily targeting proliferating T and B lymphocytes in the periphery. Teriflunomide was effective as monotherapy in reducing magnetic resonance imaging lesions and annual relapse rates in Phase II and Phase III trials. When teriflunomide was added to interferon or glatiramer acetate therapy in Phase II trials, teriflunomide reduced magnetic resonance imaging lesions significantly more than either interferon or glatiramer acetate alone. Treatment-emergent adverse events occurred at similar rates among all groups in teriflunomide studies, with a trend towards a higher treatment emergent adverse events rate in the higher dosage group of teriflunomide (14 mg daily). Treatment discontinuations in teriflunomide trials were relatively low, suggesting that teriflunomide monotherapy is well tolerated. This article reviews the mode of action of teriflunomide, its pharmacokinetic, clinical efficacy, and safety profiles.

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Section: Safety and Tolerability Of Teriflunomidementioning

confidence: 99%

Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis

Nwankwo¹,

Allington²,

Rivey³

2012

DNND

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“…PML has been described mainly in patients infected with the human immunodeficiency virus (HIV). However, other immunosuppressed patient populations, including those with malignancies, organ transplants, and systemic lupus erythematosus (SLE) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and other rheumatic diseases (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), are at risk of developing this complication.…”

Section: Introductionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

Calabrese¹,

Molloy²,

Huang³

et al. 2007

Arthritis & Rheumatism

167

102

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“…PML manifests clinically with signs of neurological deficits of various degrees, including weakness, visual deficits, and cognitive abnormalities. PML is mainly associated with advanced human immunodeficiency virus (HIV)-induced diseases and AIDS (8,9), lymphoproliferative or myeloproliferative diseases, malignancies, and rheumatic disorders treated with corticosteroids and cytotoxic drugs (1,16,25,34,39,52,58,71,75,77). Recently, PML has also been diagnosed in patients with multiple sclerosis and Crohn's disease receiving natalizumab (37,40,42,74), a humanized monoclonal antibody that binds to the ␣4 subunit of ␣4␤1 and ␣4␤7 integrins and inhibits the trafficking of leukocytes across the blood-brain barrier.…”

mentioning

confidence: 99%

JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis

Merabova

Kaniowska

Kaminski

et al. 2008

J Virol

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Productive infection of oligodendrocytes, which are responsible for the formation of myelin sheath in the central nervous system, with the human neurotropic virus JC virus (JCV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In addition to encoding T antigen and the capsid proteins, which are produced at the early and late phases of the infection cycle, respectively, JCV encodes a small regulatory protein named agnoprotein that is important for successful completion of the virus life cycle. Here we used bipotential CG-4 cells to examine the impact of agnoprotein on oligodendrocyte differentiation and survival in the absence of JCV lytic infection. We demonstrate that the expression of agnoprotein delayed the formation of complex outgrowth networks of the cells during oligodendrocyte differentiation. These alterations were accompanied by high levels of DNA damage, induction of proapoptotic proteins, and suppression of prosurvival signaling. Accordingly, apoptosis was significantly increased upon the induction of CG-4 cells toward differentiation in cells expressing agnoprotein. These observations provide the first evidence for the possible involvement of agnoprotein, independent from its role in viral replication, in a series of biological events that may contribute to the pathological features seen in PML lesions.First exposure to the human polyomavirus JC virus (JCV) commonly occurs during childhood and results in a subclinical outcome. Reactivation of the initially latent virus in individuals with impaired immune systems results in the development of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) (9,31,35). PML manifests clinically with signs of neurological deficits of various degrees, including weakness, visual deficits, and cognitive abnormalities. PML is mainly associated with advanced human immunodeficiency virus (HIV)-induced diseases and AIDS (8, 9), lymphoproliferative or myeloproliferative diseases, malignancies, and rheumatic disorders treated with corticosteroids and cytotoxic drugs (1,16,25,34,39,52,58,71,75,77). Recently, PML has also been diagnosed in patients with multiple sclerosis and Crohn's disease receiving natalizumab (37,40,42,74), a humanized monoclonal antibody that binds to the ␣4 subunit of ␣4␤1 and ␣4␤7 integrins and inhibits the trafficking of leukocytes across the blood-brain barrier.The histological hallmarks of white matter from PML patients include the appearance of oligodendrocytes with enlarged hyperchromatic nuclei that contain inclusion bodies shaped by crystalline arrays of JCV particles and astrocytes with bizarre nuclei and mitotic figures (21, 35). The presence of virions has also been demonstrated among lamellae of the myelin sheath of a viable axon (47). In cell culture systems, JCV efficiently infects primary cultures of human brain containing oligodendrocytes and astrocytes. Recent studies have shown that JCV can infect multipotential human central nervous system progenitor cells isolated fro...

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Infectious CNS disease as a differential diagnosis in systemic rheumatic diseases: three case reports and a review of the literature

Cited by 95 publications

References 59 publications

Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis

Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis

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Infectious CNS disease as a differential diagnosis in systemic rheumatic diseases: three case reports and a review of the literature

Cited by 95 publications

References 59 publications

Emerging oral immunomodulating agents &ndash; focus on teriflunomide for the treatment of multiple sclerosis

Emerging oral immunomodulating agents &ndash; focus on teriflunomide for the treatment of multiple sclerosis

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis

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Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis

Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis