Progressive multifocal leukoencephalopathy in a patient without severe lymphocytopenia receiving Dimethyl fumarate for the treatment of psoriasis


Fumaric acid esters, which are prescribed for the treatment of psoriasis and multiple sclerosis, are considered to have a favorable risk profile. However, treatment-related progressive multifocal leukoencephalopathy ( PML ) has been described in association with long-lasting, severe lymphocytopenia ( less than 500 lymphocytes per cubic millimetre ).

This has led to the recommendation that lymphocyte counts should be monitored in patients receiving these drugs in order to prevent opportunistic infections such as PML.

Researchers have reported a case of fatal PML after treatment with compounded Dimethyl fumarate ( DMF ) in a patient without severe lymphocytopenia.

On July 18, 2014, a 64-year-old woman presented with a 2-week history of progressive apraxia. She had been receiving topical glucocorticoids and compounded delayed-release DMF ( Psorinovo; compounding pharmacy, Mierlo-Hout ) for the treatment of psoriasis since June 2012.

Magnetic resonance imaging ( MRI ) of the brain showed multiple subcortical white-matter lesions. Leukocyte and lymphocyte counts were normal before Dimethyl fumarate treatment but reached a nadir of 4000 cells and 792 cells per cubic millimeter, respectively, in June 2014.

Analysis of the cerebrospinal fluid showed normal levels of leukocytes, protein, and glucose. The patient was seronegative for the human immunodeficiency virus ( HIV ).

At that time, a diagnosis of PML was considered. However, testing of the cerebrospinal fluid for JC virus DNA on polymerase-chain-reaction ( PCR ) assay was negative.

Treatment with Dimethyl fumarate was discontinued, and the patient received the diagnosis of atypical ischemic stroke.

Owing to progressive hemiparesis and somnolence, she was transferred to our hospital on August 14, 2014.

Follow-up MRI showed a rapid and widespread dissemination of lesions suggestive of PML–immune reconstitution inflammatory syndrome ( IRIS ).
Treatment with Mefloquine, Mirtazapine, and glucocorticoids was initiated.
The patient's condition continued to deteriorate, and she died on August 26, 2014.

PML was confirmed on histologic analysis of brain tissue and positive results on PCR assay for JC virus DNA in brain tissue and cerebrospinal fluid.

According to researchers, this case represents Dimethyl fumarate-associated PML, since other immunosuppressive medications or coexisting medical conditions were absent.
This is the first reported case of compounded Dimethyl fumarate–associated PML in a patient without severe lymphocytopenia, a situation that was previously thought to be unlikely.

Since the number of patients who are being treated with Dimethyl fumarate is rapidly increasing after approval of delayed-release DMF ( Tecfidera ) as first-line treatment for relapsing–remitting multiple sclerosis, the case raises important questions with respect to safety monitoring.
Although more than 100,000 patients with multiple sclerosis have been treated with Tecfidera since 2013, the safety profile for long-term treatment is unknown.
On October 22, 2014, the first case of PML in a patient receiving Tecfidera was reported; this patient had persistent, severe lymphocytopenia.
The case here reported has shown PML can develop during treatment with compounded Dimethyl fumarate in patients in whom reduced lymphocyte counts are less severe than those in cases that have been reported previously. ( Xagena )

Nieuwkamp DJ et a, N Engl J Med 2015; 372:1474-1476

XagenaMedicine_2015



Indietro

Altri articoli

The nucleoside-modified messenger RNA in COVID-19 mRNA vaccine BNT162b2 is formulated in lipid nanoparticles, which enable delivery of the RNA...


Initial preliminary findings from the Papa Giovanni XXIII Hospital sponsored SISCO ( Siltuximab In Serious COVID-19 ) Study, based on...


The FDA ( U.S. Food and Drug Administration ) has expanded the approval of Mavyret ( Glecaprevir and Pibrentasvir )...


Results from the largest study of hepatitis B and C and HIV infection prevalence in cancer patients show an alarmingly...


The FDA ( U.S. Food and Drug Administration ) has approved Dovato ( Dolutegravir and Lamivudine ), as a complete...


Integrase strand transfer inhibitor ( INSTI ) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing...


The European Commission has granted Marketing Authorisation for Dovato ( Dolutegravir / Lamivudine ) for the treatment of HIV-1 infection...


The FDA ( U.S. Food and Drug Administration ) has approved Biktarvy ( Bictegravir 50mg / Emtricitabine 200mg / Tenofovir...


Data from clinical studies confirm the efficacy of switching to Dolutegravir ( DTG ) plus Rilpivirine ( RPV ) (...


Immunotherapy has been a major breakthrough in oncology, but little is known about its safety for HIV-positive cancer patients. A...