Monday, 24 August 2015

ClinicSpeak: disseminated cryptococcal infection in an MSer on fingolimod

Another fingolimod-related opportunistic infection; will there be more? #MSBlog #ClinicSpeak #MSResearch

Fingolimod-related opportunistic infections; how many swallows make a summer? #ClinicSpeak #MSBlog

"In the case report below, Huang describes a 50-year old MSer who received fingolimod therapy and subsequently developed disseminated cryptococcal infection. He presented with 2 weeks of headache that was not associated with a fever or neck stiffness. His absolute lymphocyte count was 0.5 x 103/mm3. Brain MRI did not show any evidence of any acute pathology to explain the headache. Importantly, his MS lesions had remained stable as compared to a previous brain MRI done 1.5 years prior; in other words fingolimod was controlling his MS disease activity. He was treated for presumed diagnosis of migraine headache with a brief improvement in the headache. His headache, subsequently got worse and he developed sleepiness, nausea, vomiting, imbalance, and a facial skin lesion. The lesion was biopsied and under the microscope there showed deep soft tissue fungal infection. A CT scan of the head showed a new lesion in a part of the brain called right thalamus, which was confirmed on brain MRI that also showed numerous areas of meningeal enhancement; the latter is a sign of meningitis. Spinal fluid studies showed a lymphocytosis, high protein levels, low glucose levels and positive cryptococcal fungal antigen. CSF cultures resulted in fungal growth. Blood tests were also positive for cryptococcal antigen. He was started on anti-fungal treatment and his clinical status improved."

"This is not first case of cryptococcal infections on fingolimod I have heard about; I am aware of another case (Switzerland). One swallow doesn't make a summer, however, two swallows makes it likely that there will be more cases. Cryptococcal infection is very rare in normal people, the exception being pregnancy a state of relative immunosuppression. Cryptococcal infections is classed as an opportunistic infection and is seen in people with AIDS, malignancies, immunodeficiencies and in people on immunosuppressive drugs. Fingolimod is an immunosuppressive drug, there is little doubt it. Fingolimod now ticks almost all the boxes that define drugs as being immunosuppressive; i.e. (1) it causes a lymphopenia, (2) is associated with opportunistic infections and (3) it blunts antibody responses to vaccines. The fourth criteria is related to tumour immunosurveillance; the jury is still out about whether or not fingolimod will be associated with an increase tumour or cancer risk. I wouldn't be surprised if does increase the risk of cancers. Based on the experience in solid-organ transplants the sentinel cancers to look for will be lymphoproliferative disorders (lymphomas) and/or skin cancers."

"Does this case study change our practice? Yes, we now mention the risk of cryptococcal infection to all our patients on fingolimod and we take new-onset headaches in patients on fingolimod very seriously. One of my colleagues recently brought in one of our patients on fingolimod with a persistent headache for a lumbar puncture to exclude cryptococcal meningitis. The problem with cryptococcal meningitis is the initial symptoms can be very mild and its initial course very indolent. This is why being aware of this potential complication is important. Please remember that there are now well over 150,000 MSers who have been exposed to fingolimod so cryptococcal infection, and other opportunistic infections, are likely to be a relatively rare complication. The risk may, however, go up with treatment duration. If any more cases of cryptococcal infection, or other opportunistic infections, emerge over the next 12-24 months we may get an indication about fingolimod treatment duration being a risk factor."

Arrows point to cryptococcal fungi; Jaster & Malecha. Cryptococcal Meningitis. N Engl J Med 1996; 335:1962

Epub: Huang. Disseminated cryptococcosis in a patient with multiple sclerosis treated with fingolimod. Neurology. 2015 Aug 19. pii: 10.1212/WNL.0000000000001929.

How many swallows make a summer?

CoI: multiple


  1. Is this a pro for induction therapies? You take your risks at the beginning, and they go down over time whereas with continuous treatments your risks of opportunistic infections go up over time

  2. I had a read online a little about cryptoccocal infections and cryptoccal is a fungus. Its common in dirt and dust containing bird droppings. People who get infected have normally breathed in dirt containing the fungus. People who have HIV are advised to avoid places with high amounts of bird droppings.

  3. It sound like you are aware of what to do, but what about the not so prudent doctors that are prescribing this drug? It seems like warning labels should be added to the medication.

  4. Thanks for this post - I found your prediction of increased risk of cancers particularly relevant. As always anecdote is not data, but I was recently diagnosed with basal cell carcinoma, apparently a relatively benign form of skin cancer,after being four years on fingolimod (and doing really well on it). It sounds that I should get in touch with my neurologist, I would strongly prefer to stay on fingolomid, but I do have lymphopenia, and at the very least he needs to know what's going on.

    1. If I recall correctly fingolimod doubles your chances of developing basal carcinoma of the skin. This information will soon be included in the fingolimod label.


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