INTRODUCTION: Diagnosing neurosarcoidosis can be challenging without a CNS biopsy. However, treatment with immunosuppressive agents maybe be given in the right clinical context. Some of these agents may lead to viral reactivation ,and ultimately to lymphoproliferative disease.
CASE PRESENTATION: We present the case of a 45 year old Caucasian woman, diagnosed with pulmonary sarcoidosis in 2005 by mediastinal lymph node biopsy, who presented with new onset generalized tonic-clonic seizure. Following her initial diagnosis of sarcoidosis, she was treated with prednisone. In the year preceding her seizure, she was tapered off prednisone because of marked weight gain and treated with methotrexate 20 mg per week for persistent pulmonary symptoms. Computed tomography scans of the chest during the year prior to admission,while on methotrexate,showed worsening parenchymal disease. As part of her seizure evaluation, an MRI with contrast of the brain was performed and revealed three enhancing brain lesions .She was started on prednisone and Azathioprine for presumed neuro-sarcoidosis, Levetiracetam for seizure prophylaxis and trimethoprim-sulfamethoxazole for pneumocystis prophylaxis. Despite treatment, one month later she presented to the hospital again with a second episode of generalized tonic clonic seizure. She also experienced three instances of auras in her right visual field which had been treated with increased doses of Levetiracetam.She had no other medical problems and the rest of her history was unremarkable. Physical exam revealed a healthy middle aged woman with normal vital signs. Her physical examination, including eye and pulmonary exam was unremarkable.Routine laboratory studies were unremarkable. Repeat brain MRI showed an increase in the size of all 3 lesions.She ultimately underwent a brain biopsy of the left occipital mass.This showed hypercellular and dense lymphoid tissue infiltration ;comprised of small lymphocytes, admixed larger atypical lymphoid cells and few plasma cells; completely replacing normal brain parenchyma, consistent with Immunodeficiency associated(Epstein Barr virus associated) diffuse large B-cell lymphoma ,most likely secondary to Methotrexate therapy. PCR assay for heavy chain rearrangement was negative. EBER in situ for Epstein Barr virus was positive.She was rapidly tapered off the prednisone and Azathioprine and begun on Rituximab.
DISCUSSIONS: To our knowledge this is the first case of CNS EBV associated lymphoproliferative disorder developing while on Methotrexate therapy for sarcoidosis. One other EBV associated lymphoproliferative disorder reported in a sarcoidosis patient involved the lower gastrointestinal tract.Clinically apparent nervous system involvement occurs in about 5-15% of sarcoidosis patients. Neurosarcoidosis can occur in isolation without other organ systems involved. It can present acutely or as an insidious chronic illness. The diagnosis of neurosarcoidosis is definite when the clinical presentation is compatible with sarcoidosis and histopathology findings support direct nervous system involvement. Probable neurosarcoidosis can be diagnosed when the clinical and radiographic features are consistent with neurosarcoidosis and evidence exists of non caseating granulomas in another affected organ. We initially made a diagnosis of probable neurosarcoidosis given the previous histologic confirmation of sarcoidosis in the thorax, worsening lung disease and compatible radiographic findings. However, when disease progressed other causes were investigated . EBV associated lymphoproliferative disease has been reported in association with treatment of rheumatoid arthritis, dermatomyositis, polymyositis and psoriasis with low dose and high dose methotrexate. MTX induces reactivation of EBV from latent infection in host cells and leads to the release of infectious virions. Patients with rheumatoid arthritis or polymyositis who were treated with an MTX-containing regimen had statistically significantly higher EBV loads than patients on immunosuppressive regimens that did not include MTX. MTX also impairs the immune response to EBV.
CONCLUSION: Our case report should heighten awareness that EBV associated lymphoproliferative disease may occur during methotrexate treatment for sarcoidosis.
DISCLOSURE: Krithika Ramachandran, No Financial Disclosure Information; No Product/Research Disclosure Information