Wednesday, 23 November 2016

#ClinicSpeak & #NeuroSpeak: another case of cryptococcal infections with fingolimod

Are you a fingolimoder? Are you aware about its opportunistic infection risk? #ClinicSpeak #Neurospeak #MSBlog

I have been giving a series of talks about immunosuppression in MS and discuss the pros and cons of the different DMTs. I start off by defining what is an immunosuppressant and then discuss the different strategies for using these agents. There is a big difference between maintenance immunosuppression in which the drug is on-board all the time and the risk of opportunistic infections increases with time; i.e. the cumulative incidence increases with time and so does the risk. In comparison induction therapies, or as I prefer to call them PIRTS (pulsed immune reconstitution therapies) the risk is front-loaded and once the immune system reconstitutes the risk associated with immunosuppression drops massively. 


The case below of systemic cryptococcal infection and meningitis, an opportunistic fungal infection, in a pwMS on fingolimod is one of many cases reported worldwide. The problem with fingolimod is that you can't derisk the risk of opportunistic infections. All cases of opportunistic infection on fingolimod, to the best of my knowledge, have occurred in pwMS with lymphocyte counts above 200/mm3 or 0.2x109/L (the action level ti disruot dosing in the EU). In addition, infections in pwMS on fingolimod are not linked to the peripheral lymphocyte counts. Therefore, the only way to deal with the opportunistic infection risk on fingolimod is to remain vigilant and be aware of symptoms suggsetive of an infection. In the case of cryptococcal meningitis this may be very subtle symptoms; for example a non-specific headache or visual symptoms. The reason why cryptococcal infection is very indolent is simply because people who are immunosuppressed are unable to mount a vigorous immune response against the fungal agent concerned and hence don't present with symptoms of acute meningitis. 




Seto et al. Disseminated Cryptococcosis in a 63-year-old Patient with Multiple Sclerosis Treated with Fingolimod. Intern Med. 2016;55(22):3383-3386.

We herein report the case of a 63-year-old man who presented with a 3-month history of a cutaneous nodular lesion of his jaw, low grade fever, lethargy and progressive cognitive impairment. He had a 30-year history of multiple sclerosis and had been treated with fingolimod for the previous 2 years. Laboratory data revealed CD4 lymphocytopenia and a tissue culture of the skin nodule was positive for Cryptococcus neoformans. Cerebrospinal fluid and serum cryptococcal antigen tests were also positive and we diagnosed him to have disseminated cryptococcosis. This dissemination might be associated with fingolimod-induced CD4 lymphocytopenia. The risk of an opportunistic infection should therefore be considered when encountering fingolimod-treated patients.


CoI: multiple

4 comments:

  1. Any cases of fungal infections on the other DMTs?

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  2. Replies
    1. It's a fungus-mimicking bacterium that can cause opportunistic infections in those with weakened immune systems. Commonly found in soil.

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  3. Mouse Dr, Ocrelizumab only shows 23% reduction. But the % of possible infections compared to say DMT Copaxone? And if Copaxone has 30-35% better protection, without the % of these infections, am I missing something? Biotin? Polysaccharides A PSA for gut bacteria?

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