Progressive multifocal leukoencephalopathy and CD4+ T-lymphocytopenia in a patient with Sjögren syndrome

doi:10.1016/j.jns.2007.12.015

Journal of the Neurological Sciences

Volume 268, Issues 1–2, 15 May 2008, Pages 195-198

https://doi.org/10.1016/j.jns.2007.12.015 Get rights and content

Abstract

We report progressive multifocal leukoencephalopathy (PML) and CD4+ T-lymphocytopenia in a 71-year-old man with Sjögren syndrome (SjS). The patient was admitted to our hospital because of progressive dementia and gait disturbance. T2-weighted MR images showed high-intensity lesions in his left frontal white matter thalamus, cerebellum and brainstem. A pathological diagnosis of PML was made by brain biopsy. SjS is frequently accompanied with immunological complications; however, there are few reports on PML in patients with SjS. Recently, isolated CD4+ T-lymphocytopenia is reported to be one of the based immunological conditions associated with the development of PML. In the present case, CD4+ T-lymphocytopenia was also observed on admission, which is also associated with SjS.

Introduction

Progressive multifocal leukoencephalopathy (PML), which is caused by the JC virus (JCV), usually develops as a central nervous system (CNS) opportunistic infectious disease in immunocompromised patients, such as those with acquired immunodeficiency syndrome (AIDS), a variety of collagen diseases, or those who are undergoing steroid hormone or immunosuppressive therapy [1]. Sjögren syndrome (SjS) is one of the collagen diseases and highly accompanied with immunological complications. However, to date, the disease has not been considered to be a high risk factor of PML. Here we report a rare case of PML developing in an aged patient with SjS accompanied with CD4+ T-lymphocytopenia.

Section snippets

Case report

The patient, a 71-year-old Japanese man with a 5-year history of primary SjS, was admitted to our hospital because of progressive dementia and gait disturbance that were observed 2 months and 1 month before his visit, respectively. His first symptom of SjS was dry mouth. His diagnosis of SjS was made 5 years ago by Saxon and Shirmer tests, scintigraphy of the parotid and submandibular glands, and lip biopsy that revealed many lymphocytes and plasma cells infiltrating the small salivary glands.

Discussion

We have described a case of PML with SjS, in which progressive dementia, right hemiparesis, and truncal and limb ataxia were the clinical features.

In this case, tumefactive multiple sclerosis (MS), cerebral vasculitis with SjS and primary CNS malignant lymphoma were initially considered as differential diagnoses from the MRI findings.

IMP-SPECT images demonstrated delayed high accumulation of IMP in the left frontal white matter. Primary CNS malignant lymphoma, malignant astrocytoma, and

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Pseudotumoral brain lesion as the presenting feature of primary Sjögren's syndrome
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Our patient with established pSS exhibited a pseudotumoral lesion. Differential diagnosis including lymphoma and progressive multifocal leukoencephalopathy, which are potential complications of pSS [7,8], was excluded particularly with regard to the spontaneous favorable outcome. Although described in other autoimmune CNS diseases like MS, tumefactive lesions have been rarely reported in pSS [9,10].
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The present case suggests that a pseudotumoral brain lesion can occur as an initial symptom of pSS.
Progressive multifocal leukoencephalopathy in autoimmune diseases
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The main systemic diseases associated with PML are the vasculitides [13], most notably Wegener's granulomatosis [38,39] and poly- or dermatomyositis [7,40]. A few cases have been reported in patients with scleroderma [7] or Sjogren's syndrome with CD4+ counts lower than 300/mm3 [41]. At present, no tools are available for preventing or evaluating the risk of PML in patients with chronic inflammatory joint diseases associated with autoimmune disorders.
Progressive multifocal leukoencephalopathy (PML) is a subacute central nervous system infection due to reactivation of the JC virus. Most reported cases occurred in HIV-infected patients (80% of cases), patients with lymphoid malignancies (13%) and transplant recipients taking immunosuppressants (5%). Less often, PML has been described in patients with chronic inflammatory joint diseases associated with autoimmune disorders (lupus, rheumatoid arthritis [RA] and vasculitis) (2%). Magnetic resonance imaging of the brain shows suggestive changes and confirmation of the diagnosis is obtained by performing PCR tests to identify the JC virus in the cerebrospinal fluid or, when necessary, a brain biopsy. No treatments have been proven effective. Most patients experience progressive disease that is fatal within a few months or induces incapacitating neurological impairments. The risk of PML is 0.4/100 000 in patients with RA. In the few case-reports of PML in RA patients, the treatments used included methotrexate (five cases) combined with a biological agent such as infliximab (one case), rituximab (four cases), or leflunomide (two cases including one with concomitant rituximab). PML is an extremely rare but devastating complication. Rituximab therapy is associated with an increased prevalence of PML in RA patients (4/100 000), who should be informed of this risk. In patients with lupus, the risk of PML is higher than in RA (4/100 000) and 40% of cases of PML occur during low-dose glucocorticoid therapy without immunosuppressive therapy.
Progressive multifocal leukoencephalopathy in autoimmune diseases
2012, Revue du Rhumatisme (Edition Francaise)
La leucoencéphalite multifocale progressive (LEMP) est une infection subaiguë du système nerveux central due à la réactivation du virus JC. Elle a été principalement décrite chez les patients infectés par le VIH (80 % des cas), au cours des maladies hématologiques lymphoïdes malignes (13 %), chez les transplantés sous traitement immunosuppresseur (5 %) mais également dans les rhumatismes inflammatoires chroniques à composante auto-immune (lupus, polyarthrite rhumatoïde [PR], vascularite) (2 %). Le diagnostic repose sur l’aspect IRM évocateur et la mise en évidence du virus JC par PCR dans le LCR ou à la biopsie cérébrale qui est parfois nécessaire. En l’absence de traitement reconnu, l’évolution se fait dans la majorité des cas vers l’aggravation et est le plus souvent fatale en quelques mois ou s’accompagne dans les meilleurs cas de séquelles neurologiques invalidantes. Le risque de développer une LEMP est de 0,4/100 000 dans la PR. Quelques cas rapportés au cours de la PR ont détaillé les traitements utilisés : méthotrexate (cinq cas), associés à une biothérapie comme l’infliximab (un cas), le rituximab (quatre cas) et, le léflunomide (deux cas) dont un cas en association au rituximab. La survenue de cette complication très grave est très rare. En cas de traitement par rituximab, la prévalence est augmentée (4/100 000) dans la PR ce qui nécessite d’en informer le patient. Au cours du lupus, le risque de LEMP est plus élevé (4/100 000) qu’au cours de la PR et peut survenir dans 40 % des cas en l’absence de traitement immunosuppresseur sous une corticothérapie à faible dose.
Progressive multifocal leukoencephalopathy in patients with rheumatic diseases: Are patients with systemic lupus erythematosus at particular risk?
2008, Autoimmunity Reviews
Citation Excerpt :
Overall, of the additional 10 cases mentioned above, 7 patients had SLE [2,3,5,7,8]. Of the other 3 patients, 1 had RA [8], one patient had a 3 year history of destructive polyarthritis and Raynaud's phenomenon with positive ANA and Jo1 antibodies and CD4+ lymphopenia [6] and one patient developed PML in the setting of Sjögren's syndrome and CD4+ lymphopenia [4]. Reported cases of proven PML in patients with rheumatic diseases are summarized in Table 1.
Progressive multifocal leukoencephalopathy (PML) is a rare, frequently fatal, infectious complication occurring in immunocompromised patients. PML has been well-reported in patients with chronic inflammatory rheumatic diseases taking immunosuppressive drugs. Awareness of the occurrence of PML in patients with rheumatic diseases has recently been highlighted by the occurrence of several cases of PML following administration of natalizumab and rituximab, biologic agents which have been used for the treatment of rheumatic diseases. Nearly two thirds of cases of PML in patients with rheumatic diseases reported in the medical literature occurred in patients with systemic lupus erythematosus (SLE). Over 40% of PML cases in SLE occurred in patients who had had minimal iatrogenic immunosuppression, suggesting that SLE itself may predispose to PML. The mechanism of this putative predisposition of SLE patients to the development of PML remains unexplained.

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Short communicationProgressive multifocal leukoencephalopathy and CD4+ T-lymphocytopenia in a patient with Sjögren syndrome

Abstract

Introduction

Section snippets

Case report

Discussion

Virology

Am J Ophthalmol

Clin Diagn Virol

Review of progressive multifocal leukoencephalopathy and natalizumab

Neurologist

Unusual uptake and retention of I-123 IMP in brain tumors

Clin Nucl Med

High 123I-IMP retention on SPECT image in primary central nervous system lymphoma

J Neuro-Oncol

Evaluating brain tumors with SPECT

J Med Soc Toho

Increased accumulations of N-isopropyl-p-[123I]-iodoamphetamine related to tumefactive multiple sclerosis

Ann Nucl Med

Oligoclonal measles virus-specific antibodies isolated from cerebrospinal fluids, brain extracts, and sera from patients with subacute sclerosing panencephalitis and multiple sclerosis

Scand J Immunol

Short communication
Progressive multifocal leukoencephalopathy and CD4+ T-lymphocytopenia in a patient with Sjögren syndrome

High ¹²³I-IMP retention on SPECT image in primary central nervous system lymphoma

Increased accumulations of N-isopropyl-p-[¹²³I]-iodoamphetamine related to tumefactive multiple sclerosis