A human T-lymphotropic virus-1 carrier who developed progressive multifocal leukoencephalopathy following immunotherapy for sarcoidosis: a case report

Abstract

Background: Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disorder of the central nervous system caused by opportunistic infection of the JC virus (JCV).

Case presentation: A 58-year-old Japanese woman was admitted to our hospital for aphasia. She had a 5-year history of untreated sarcoidosis and was a human T cell lymphotropic virus-1 (HTLV-1) carrier. Serum angiotensin-converting enzyme, soluble interleukin-2 receptor, lysozyme, and calcium levels were elevated. JCV-DNA was not detected in cerebrospinal fluid by PCR testing. Skin biopsy revealed noncaseating granuloma formation. Bilateral multiple nodular lesions were present on chest X-ray. Brain magnetic resonance imaging showed left frontal and temporal lesions without gadolinium enhancement. As we suspected that systemic sarcoidosis had developed into neurosarcoidosis, we started steroid and infliximab administration. After treatment, the chest X-ray and serum abnormalities ameliorated, but the neurological deficits remained. At 1 month after immunotherapy, she developed right hemiparesis. Cerebrospinal fluid was positive for prototype (PML-type) JCV on repeated PCR testing. Brain biopsy revealed demyelinating lesions with macrophage infiltration, atypical astrocytes, and JCV antigen-positive cells. We diagnosed her with PML and started mefloquine, leading to partial remission.

Conclusions: Sarcoidosis and HTLV-1 infection both affect T cell function, especially CD4⁺ T cells, and may developped the patient's PML. The comorbidity of sarcoidosis, PML, and HTLV-1 infection has not been reported, and this is the world's first report of PML associated with HTLV-1 infection and sarcoidosis.

Keywords: Case report; Demyelination; Human T-lymphotropic virus-1 (HTLV-1); Progressive multifocal leukoencephalopathy (PML); Sarcoidosis.

Fig. 1

Skin lesions and chest imaging findings on admission. A A brownish skin lesion with a diameter of 3 cm was observed on the left knee. B Chest computed tomography revealed bilateral infiltrating band-like opaque lesions. C Chest positron emission tomography revealed diffuse accumulation in the lung lesions. D Skin biopsy hematoxylin–eosin (HE) staining showed noncaseating granuloma formation with multinucleated giant cells. Scale bar: 50 μm

Fig. 2

Brain magnetic resonance imaging on admission. Brain magnetic resonance imaging showed a hyperintense lesion in fluid-attenuated inversion recovery imaging (A), diffusion-weighted imaging (B), and apparent diffusion coefficient mapping (C) (arrows) in the left temporal lobe. T2-weighted images also show high-intensity lesions (D, E). There was also a left frontal lobe lesion (F, arrow). These lesions lacked gadolinium enhancement (G, H, arrows)

Fig. 3

Brain magnetic resonance imaging after neurological deterioration. Brain magnetic resonance imaging showed an enlargement of the left frontal lobe lesion with hyperintensity in fluid-attenuated inversion recovery imaging (A), diffusion-weighted imaging (B), T2-weighted image (C, inset), and apparent diffusion coefficient mapping (D) with a “milky way appearance” (arrow). This lesion still lacked gadolinium enhancement (E) with “milky way appearance” in post-gadolinium enhancement (E, inset)

Fig. 4

Pathological findings of a brain biopsy from the left frontal lesion. A, B In low-magnification view of hematoxylin–eosin (HE) and Klüver-Barrera (KB)-stained sections. The sampled lesion consisted of inflammatory cell infiltration and myelin loss. C, D High-magnification view of HE. HE staining showed foamy macrophage infiltration and atypical astrocytes. E KB staining demonstrated demyelination with myelin-laden macrophages. F Double-staining of KB and neurofilament immunostaining revealed relatively preserved axonal structures compared to myelin. G Immunostaining showed that the infiltrating cells were CD68 ⁺ . H Immunohistochemistry using an anti-JCV VP2/3 antibody indicated the presence of JC virus antigen-positive cells. Scale bars: 200 μm (A, B), 20 μm (C–F, H), and 50 μm (G)