Hepatic microabscesses during CMV reactivation in a multiple sclerosis patient after alemtuzumab treatment

Barone, Stefania; Scannapieco, Sara; Torti, Carlo; Filippelli, Enrica; Pisani, Vincenzo; Granata, Alfredo; Console, Domenico; Demonte, Giulio; Tallarico, Tiziana; Polidoro, Serena; Quattrone, Aldo; Valentino, Paola

doi:10.1016/j.msard.2017.12.009

Cited by 12 publications

(5 citation statements)

References 11 publications

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“…Incidences of severe herpes virus infections led to the implementation of testing for antibody to VZV before starting alemtuzumab treatment and to consider the vaccination of antibody-negative patients, as well as a prophylactic anti-herpes virus treatment with acyclovir during the first month after alemtuzumab infusion [86]. An increased risk of human papillomavirus cervicitis (HPV) [78] and occasional cases of cytomegalovirus (CMV) disease have been described [79,[87][88][89]. The prognostic characteristics and risk factors for opportunistic infections in MS patients treated with alemtuzumab have yet to be accurately assessed.…”

Section: Infection Riskmentioning

confidence: 99%

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Rolla

Maglione

Mercanti

et al. 2020

Cells

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Alemtuzumab is a monoclonal antibody that binds to CD52, a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes are derived. It is currently used as an immune reconstitution therapy in patients with relapsing–remitting multiple sclerosis. Alemtuzumab treatment is an intermittent infusion that induces long-term remission of Multiple Sclerosis also in the treatment-free period. After the robust T and B cell depletion induced by alemtuzumab, the immune system undergoes radical changes during its reconstitution. In this review, we will discuss the current knowledge on the reconstitution of the lymphocyte repertoire after alemtuzumab treatment and how it could affect the development of side effects, which led to its temporary suspension by the European Medical Agency.

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Section: Infection Riskmentioning

confidence: 99%

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

Rolla

Maglione

Mercanti

et al. 2020

Cells

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“…HCV exacerbation and possibly reactivation have also been described in patients receiving alemtuzumab therapy [180,181]. Furthermore, cases of HEV-related acute hepatitis [182], cytomegalovirus-related hepatitis [183], and adenovirus hepatitis [184] after alemtuzumab therapy have been reported (Table 4).…”

Section: Alemtuzumabmentioning

confidence: 98%

The Disease-Modifying Therapies of Relapsing-Remitting Multiple Sclerosis and Liver Injury: A Narrative Review

et al. 2021

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In this narrative review, we analyze pre-registration and post-marketing data concerning hepatotoxicity of all disease-modifying therapies (DMTs) available for the treatment of relapsing-remitting multiple sclerosis, including beta interferon, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, cladribine, natalizumab, alemtuzumab, and ocrelizumab. We review the proposed causal mechanisms described in the literature and we also address issues like use of DMTs in patients with viral hepatitis or liver cirrhosis. Most data emerged in the post-marketing phase by reports to national pharmacovigilance agencies and published case reports or case series. Serious liver adverse events are rare, but exact incidence is largely unknown, as are predictive factors. Unfortunately, none of the DMTs currently available for the treatment of multiple sclerosis is free of potential hepatic toxic effects. Cases of acute liver failure have been reported for beta-interferon, fingolimod, natalizumab, alemtuzumab, and ocrelizumab by different mechanisms (idiosyncratic reaction, autoimmune hepatitis, or viral reactivation). Patients with multiple sclerosis should be informed about possible hepatic side effects of their treatment. Most cases of liver injury are idiosyncratic and unpredictable. The specific monitoring schedule for each DMT has been reviewed and the clinician should be ready to recognize clinical symptoms suggestive for liver injury. Not all DMTs are indicated in cirrhotic patients. For some DMTs, screening for hepatitis B virus and hepatitis C virus is required before starting treatment and a monitoring or antiviral prophylaxis schedule has been established. Beta interferon, glatiramer acetate, natalizumab, and alemtuzumab are relatively contraindicated in autoimmune hepatitis due to the risk of disease exacerbation.

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“…Acyclovir prophylaxis is also indicated in patients receiving cladribine with severe lymphopenia (grade IV: lymphocyte count <200 cells/μL). 3 Cases of CMV infection have recently been reported in patients with MS treated with alemtuzumab, 19,20 but there is insufficient available evidence to state that there is an increased risk with DMD therapy (statement 2.7). and natalizumab.…”

Section: Opportunistic Infectionsmentioning

confidence: 99%

The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement

et al. 2020

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The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.

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Hepatic microabscesses during CMV reactivation in a multiple sclerosis patient after alemtuzumab treatment

Cited by 12 publications

References 11 publications

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

The Disease-Modifying Therapies of Relapsing-Remitting Multiple Sclerosis and Liver Injury: A Narrative Review

The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement

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