Progressive multifocal leucoencephalopathy in a patient with Sézary syndrome
Authors: C. Le Roux-Villet, L. Michel, J. Gasnault, Y. Taoufik, H. Bachelez
Journal: British Journal of Dermatology (2010)

Conflicts of interest: H.B. has carried out consultant activities for Abbott, Cephalon‐Zeneus, Janssen‐Cilag, Merck‐Serono, Schering‐Plough, Wyeth Pharmaceuticals. J.G. has received travel grants, consultancy fees or honoraria from Abbott, Bristol‐Myers‐Squibb, Gilead Sciences, Glaxo‐Smith‐Kline, Janssen‐Cilag‐Tibotec and Roche. The authors declare no conflict of interest. Madam, Progressive multifocal leucoencephalopathy (PML) is a subacute, life‐threatening demyelinating disease of the brain caused by reactivation of the JC virus (JCV), which has been reported in severe immunosuppression related to cancer, organ transplantation or acquired immune deficiency syndrome (AIDS).1, 2 We report the first case of PML occurring in a patient treated for Sézary syndrome, a leukaemic variant of primary cutaneous T‐cell lymphoma (CTCL). A 48‐year‐old man was referred for a generalized eruption lasting for 2 years. He had a history of tonsil carcinoma, treated 5 years previously with combined surgery, radiation and chemotherapy with further sustained complete remission. The diagnosis of Sézary syndrome was established by skin histology, and detection of circulating Sézary cells (1200 cells μL−1) and of a T‐cell clone in skin and blood. Treatment with interferon alfa 5 million units (MU) 5 days per week led to a clinical response, without evidence of any residual circulating Sézary cells, while the peripheral blood clonality status returned to polyclonal. Three years later, the interferon alfa dosage was increased to 7 MU daily 5 days per week because of a relapse; this led to a dramatic improvement. After another 3 years, treatment was switched from interferon alfa to bexarotene 300 mg m−2 daily due to evolving disease. Two weeks later, the patient was admitted for a left arm neurological motor defect, with hemianopsia and disorientation. Magnetic resonance imaging showed T2‐weighted hyperintense lesions in the parietal and occipital lobes. The diagnosis of PML was confirmed by the positive detection of JCV DNA by polymerase chain reaction‐based analysis of a cerebrospinal fluid sample. Serological tests for human immunodeficiency virus (HIV)‐1/2 and human T‐cell lymphotropic virus‐I were negative. Peripheral blood lymphocyte (PBL) absolute count was 1840 cells μL−1, with 1309 CD4+ T cells μL−1, most of them lacking CD7 expression and 240 CD8+ T cells μL−1, and a normal CD19+ B‐cell count of 79 μL−1. Flow cytometry analysis of the PBL repertoire using monoclonal antibodies to T‐cell receptor β variable (TCRVβ) segments showed that TCRVβ17+ cells represented more than 84% of all CD4+ cells (Fig. 1). Finally, functional analysis of T cell‐mediated proliferative responses was performed using the patient’s PBLs and control PBLs from healthy donors. This addressed proliferative responses to mitogenic stimulus by phytohaemagglutinin and JCV‐specific CD4+ T‐cell responses by using a proliferative assay to purified JCV (Mad‐4 strain) as previously described.3 As shown in Table 1, a striking defect in the JCV‐specific response was observed using the patient’s PBLs, while no defect of response to mitogenic stimuli could be detected. Treatment with cidofovir and cytosine arabinoside was initiated but the patient died 1 month later after neurological worsening and severe pneumonia.