Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus and autoimmune hepatitis

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating central nervous system illness encountered in the setting of immunosuppressive conditions like human immunodeficiency virus / acquired immunodeficiency syndrome, autoimmune diseases and hematologic malignancies. We had a 54-year-old woman with systemic lupus erythematosus and coexisting autoimmune hepatitis who presented with progressive cognitive decline, right hemiparesis and ataxia who was found to have PML. She had severe CD4 lymphopenia. She was managed with low-dose prednisolone and plasma exchange after which she showed significant clinical improvement. This case highlights the diagnostic and therapeutic challenges encountered in managing a case of PML in the setting of autoimmune conditions with profound lymphopenia.

Progressive Multifocal Leukoencephalopathy in Systemic Lupus Erythematosus: A Consequence of Patient-Intrinsic or -Extrinsic Factors?

“…This observation, coupled with the excessive PML risk in lupus [1,7], has put forward the hypothesis that disease-intrinsic immune deregulation might contribute to JCV activation. In this regard, lymphopenia, especially of CD4+ T cells, has been proposed as a risk factor for PML in SLE [6,[10][11][12] and other individuals [27]. Lymphopenia is considered a typical disease manifestation of lupus, although it may also occur as a side effect of administered immunosuppressive therapy.…”

“…To this end, effective treatment of PML in non-HIV individuals such as those with SLE represents a major unmet need. Nonetheless, there is rationale to explore immune-directed modalities, and accordingly, the possible utility of exogenous IL-2 and IL-7 to expand the pool of CD4+ T cells has been proposed [12].…”

“…To this end, no robust risk factors for SLE-associated PML have been identified so far, although such an endeavor is arduous due to the rarity of the disorder [7]. Nonetheless, previous studies have implicated lymphopenia, especially of the CD4+ T-cell compartment, as a predisposing factor [6,[10][11][12]. Still, the majority of SLE patients with lymphopenia will not develop PML during their lifetime; therefore, the etiopathogenesis of JCV activation/PML in this context remains elusive.…”

John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis

“…For instance, PML has been associated with chemotherapy-induced lymphocytopenia in solid tumors and it has been recorded in a case with follicular lymphoma treated with anti-CD20 monoclonal antibodies, and another spontaneous report was on a patient undergoing treatment for advanced ductal breast carcinoma and systemic sclerosis who developed the disease, whereas it has been discussed that atypical findings should not exclude diagnosis in cases that are not likely to have classical PML [49][50][51][52]. PML has been documented in people with various autoimmune-supposed conditions-apart from MS-who follow immunomodulation therapy, like Systemic Lupus Erythematosus (SLE) in parallel with cancer complications or not, Rheumatoid Arthritis (RA), ANCA-associated vasculitis, autoimmune hepatitis, myositis, ulcerative colitis, lupus nephritis, ankylosing spondylitis and Crohn's disease [53][54][55][56][57][58][59][60][61][62]. Also, PML has possibly been evident in a case with Coronavirus Disease 2019 (COVID-19) as well as in a patient with Hepatitis B virus-induced CD4 lymphocytopenia, while the disease may occur in the context of systemic sarcoidosis without immunosuppression in which it can even be the first sign, and it can initially be mistaken for neurosarcoidosis or other complications of sarcoidosis [63][64][65].…”