Wednesday, 22 March 2017

ClinicSpeak; gardening post-alemtuzumab

Another opportunistic infection associated with alemtuzumab use in a person with MS. #MSBlog #ClinicSpeak

Question: "I am day 12 day after last alemtuzumab dose and probably have lymphopenia/leukopenia at the moment. Should I avoid the garden this spring :-(?"

Answer: Yes, you are putting yourself at risk of Nocardial infection. Nocardia species live in the soil. There have been cases described post alemtuzumab (see below). 


The first case below presented with a 3-week history of cough, shortness of breath, and a high fever 8 weeks after the first cycle of alemtuzumab treatment. Nocardia are aerobic gram-positive bacteria found in soil and water.  Nocardia is an opportunistic infection and needs to be taken very seriously. At the moment nocardial infections are rare and I am not sure what the risk is post-alemtuzumab. However, whilst you are neutropaenic and lymphopaenic I would advise avoiding soil exposure. 

Nocardia in the brain at autopsy; image from Wikipedia

Sheikh-Taha & Corman. Pulmonary Nocardia beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis. Mult Scler. 2017 Feb 1:1352458517694431.

Nocardia is a Gram-positive aerobic pathogen that usually affects immunocompromised patients. We report a case of pulmonary infection caused by a rare Nocardia species, Nocardia beijingensis, in a 50-year-old woman who had received alemtuzumab for the treatment of her multiple sclerosis. The invasive pulmonary infection was successfully treated with meropenem.

Penkert et al. Fulminant Central Nervous System Nocardiosis in a Patient Treated With Alemtuzumab for Relapsing-Remitting Multiple Sclerosis. JAMA Neurol. 2016 Jun 1;73(6):757-9.

16 comments:

  1. Aren't I feeling rather foolish right now. Was aware, thanks to this site, of the risk of Nocardiosis post first dose of Alemtuzumab, but happily went back to gardening at the start of this month. Assumed that if I was uber careful with wearing gloves and hand washing I'd be fine, because it is contracted from soil or water. Didn't realise inhalation is an issue! Will you please advise how long gardening should be avoided. Thanks.

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  2. Further to my query a couple of mins ago about how long post Alemtuzumab to avoid gardening I'm hoping you can tell us ProfG about when we might benefit from the guest post concerning infections and other risks post infusion. I found the list of things a recipient of Alemtuzumab is vulnerable to helpful - listed on my phone under health data. Now I'd really like to have more advice and guidance.
    Thanks.

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  3. Fi, this is the time of the year when the gardeners just can't wait to start digging, planting, potting up and so on :-), I totally understand that as the energy levels go up we want to return to the activities we love. ( as I started feeling better after 2 or 3 steroid infusions in the Lemtrada course, I transplanted all my seedlings in the alemtuzumab week :-/. My plant babies are doing fine, I wonder how I'll be doing in a few months.

    I tend to think of The British as a nation of gardeners, everybody seems to have this little "front bit" and a perfect lawn with a flowery border at the back of the house :-). I hope the information people get from Genzyme/Sanofi in the UK is better - I got a brochure with "important information" ( it covers ITP, anti-GBM, thyroid problems... and the last sentence in it is that patients treated with Lemtrada have higher risk of severe infections, but nothing about what I can do to prevent them (!!!).
    I also got a booklet "Handbook for HCP about Lemtrada treatment" which is mostly about "thoughts and feelings" and it is as if they cannot quite make up their mind if they are talking to me as a patient or my neurologist. None of them mentions opportunistic infections.

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  4. Prof G, I hope you answer Fi's question about when it is safe to "return to play" as sports medicine doctors would say.

    I have tried to look for some more information and found this article that is a bit optimistic in its conclusion - based on 447 patient years (which, let's face it is nothing if you think of opportunistic infections).
    Is it time to update this optimistic view? it allows Genzyme to feed both doctors and patients these brochures about "feelings" rather than compromised immune system for months to come.
    They had Listeria in CAMMS already, then there have been more Listeria cases in the real world.
    Nocardia is maybe not the easiest thing to diagnose, so unless clinicians think about it may not be diagnosed and treated in time.

    https://www.ncbi.nlm.nih.gov/pubmed/22056965

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    1. With regard to Listeria most of the cases I am aware of have become infected within the first 4 weeks. We are currently recommending 3 months on the diet post-alemtuzumab infusion. Based on this it would be sensible to have the same advice for Nocardia. The other option is to use a mask and gloves whilst gardening to avoid soil exposure.

      We are highly likely to introduce trimethoprim-sulfamethoxazole (co-trimoxazole) prophylaxis for Listeria, which will cover Nocardia as well.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498414/

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    2. Thanks for the additional clarification ProfG.
      Among many other things of benefit to HCP and PwMS, this site is privotal for the provision of not only bang-up-to-date info concerning DMTs but also the refinement of the frustratingly generic advise and guidance provided by pharma and every other site. Just as CD20cell has intimated, online searches can prove limited and frustrating. The requirements for self care/monitoring need this kind of detail.
      Hopefully the two of us and our fellow gardeners (yes it is good for our mood) can now confidently return to our lawns and beds.
      Hope ProfG you get to enjoy the sunshine forecast this weekend.

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    3. I want to reiterate that the incidence of Nocardia post-alemtuzumab is very uncommon (< 1 in 1,000) and possibly even rare (< 1 in 10,000). I can't give you accurate figures as I don't have access to them.

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    4. It is probably wise to cover for opportunistic infections. Listeria is maybe easier to control, most people can probably manage without unpasteurised milk products and deli meats.
      Nocardia is probably more ubiquitous than we would like to think, how does one avoid wind carrying particles from decomposing leaves in a park.
      And I would be the first to admit that compliance with "no gardening" rule is virtually impossible. I have 30+ house plants anyway, even if I got rid of them today I cannot get rid of what there is around the house already. This is quite funny, I have never thought of green house plants as a health hazard!

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    5. I wonder if all cases are diagnosed and reported, though. We only find what we look for, most of the time. Everybody has by now heard of PML on Tysabri, I am not sure they are as familiar with Nocardia.

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    6. And I was wondering if we know how many MS patients have been treated with alemtuzumab to date... or patient years of exposure

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    7. CO20cell, like you, I'd contemplated the potential hazards from my house plants as well,though a mere half dozen.
      I appreciate your coming back to put the incidences of Nocardia into context, ProfG, however I'm definitely of the view that it's very helpful to have the parameters you have recommended,in view of the risk when undertaking activities such as gardening. The advice is allows for us to engage in daily life confident of being as safe and well as possible .My husband managed to get Metallica tickets for himself and my son this morning and I laughingly said your reply was the equivalent of 'my ticket' Thanks again.

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    8. As at the end of 2016 12,000 patients have been treated with Lemtrada.

      Source: http://en.sanofi.com/Images/49329_Cowen_032017_final.pdf

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    9. Thank you, Anonymous 2:56. That is not a large number.

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  5. Prof G, uptodate actually says that PCP prophylaxis is indicated in patients receiving alemtuzumab - which boils down to the same co-trimoxazole covering all three (Nocardia, Listeria and PCP). I am considering it, just haven't decided on the dose.

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    1. CD20cell, my centre prescribed 2x 480mg co-trimoxazole every morning for 4 weeks following treatment. This was following the very sad death of an MS patient from Listerial meningitis associated with alemtuzumab last year. My bottle tells me that it cost the princely sum of £5.40, which seems pretty cheap for something potentially life-saving.

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    2. Hatty Beanbag, this is interesting because I think Britian is slightly ahead of everyone else on Lemtrada. I think our neurology dept. is taking a bit of a mickey here, but it is partly powered by Genzyme downplaying the risk of infections. "Live as normally as possible" is not good advice to somebody with no lymphocytes.
      Infections were 20% more common in patients on Lemtrada, the risk of serious infections was double on Lemtrada (but still low 2% Lemtrada versus 1% on iterferon). Not much, but some of the infections could be avoided by common sense advice or some antibiotics for a month, then why not do it?
      The price of co-trimoxazole is ridiculous so I happily took it as an out-of-pocket expense rather than starting a dispute with my neuro. But I have used it before and know that I tolerate it well (some people get really bad reactions to it, so it is not a solution that fits all).

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