Ep 30. Diagnosing cocaine-induced vasculitis

How can you differentiate between cocaine-induced and ANCA-associated vasculitis? Dr Sander van Leuven joins Dr David Liew to discuss a recent case series analysis from centres in Birmingham and London.

Sander is a consultant rheumatologist in Nejmegen, the Netherlands. He previously trained in London, where he conducted a 15-year retrospective study of cocaine-associated pseudovasculitis.

Want to find out more? Here's your further reading list:

1. Case series analysis from Gill et al.
2. Sander's accompanying editorial (plus excellent graphic!)
3. Sander's 2018 case series, published in Autoimmunity Reviews

Thanks for listening to Talking Rheumatology Research! Join the conversation on X using #TalkingRheumResearch, tweet us @RheumJnl, or find us on Instagram and LinkedIn.

Want to read more rheumatology research? Explore Rheumatology and Rheumatology Advances in Practice.

Transcript

Voiceover  0:15 
You're listening to the Talking Rheumatology Research podcast, brought to you by the British Society for Rheumatology.

David Liew  0:29  
Welcome to the Talking Rheumatology Research podcast from BSR journals. I am David Liew, rheumatologist and clinical pharmacologist in Melbourne, Australia, and today we'll be talking a little bit about cocaine-induced vasculitis. This really comes off the back of an article in Rheumatology Advances in Practice, as well as an editorial which followed that from Sander van Leuven who has joined me today. Sander, would you mind introducing yourself?

Sander van Leuven  0:56 
Yes. Hi, David. So my name is Sander van Leuven and I've been working as a consultant rheumatologist in the city of Nijmegen in the Netherlands since 2016 now if I remember correctly, and before that I did my training in Amsterdam in the Netherlands but also in London in England.

David Liew  1:15 
And I mean, I think that's particularly pertinent to this particular issue as we'll get into. You've written this beautiful editorial with a lovely graphic as well. The editorial is entitled 'Hidden in plain sight: how to look behind the veil of cocaine-induced vasculitis'. And really I think it's about appreciating that, apart from just those cocaine-induced midline destructive lesions, which can mimic ANCA-associated vasculitis, apart from those we have this increasing appreciation about cocaine-induced vasculitis looking like ANCA-associated vasculitis. Can you tell us a little bit about how this has evolved over time and what it looks like in practice?

Sander van Leuven  1:58 
Yes, absolutely. I think it's a very good question. Cocaine-induced vasculitis can mimic closely ANCA-associated vasculitis and that can make a diagnosis very hard to differentiate. The ANCA-induced vasculitis can manifest itself in different ways, similar to to an ANCA-associated vasculitis in the sense that you can have isolated ENT problems or skin involvement, but also lung or kidney involvement. So from a clinical perspective, it can be very difficult to distinguish between the two entities, but nevertheless, it's extremely important that you distinguish them because treatment can be quite different. And I think what the paper from Dr. Gill has very nicely shown is that if you do urinalysis, in all your patients, you're going to find more cocaine induced vasculitis than you originally thought. And that goes back to the beginning of the clinical process, I guess, where you may want to lower the threshold for cocaine testing in urine.

David Liew  3:01 
And I mean, sometimes autoantibodies can differentiate a drug-induced disease away from classical disease, but possibly less so in this case - would that be fair to say?

Sander van Leuven  3:11 
Yeah, I agree. I think that in the vast majority of cocaine-induced vasculitis, they have positive ANCA-antibodies - so I think about 90%. But in a very large part of these patients, you will see a very atypical pattern, so that doesn't help you further. There have been some earlier reports, where the researchers felt that dual positivity, so PR3 and MPO antibodies, could be pathognomonic for cocaine-induced vasculitis, but the current study shows that that's not necessarily true. And also in earlier large ANCA-associated trials, they found dual positivity, so just by going on the antibodies, it's not going to be enough to distinguish these two disorders from each other.

David Liew  4:00 
And I guess it's particularly the case that you can't necessarily just tell who's a cocaine user from looking at them from the end of the bed. I think I've been shocked as to how widespread cocaine use is, particularly in the UK.

Sander van Leuven  4:15 
Yeah, the use of cocaine seems to be rising exponentially. If you look at the latest UN report, I think in the period between 2014 and 2020, it almost doubled. And so that must also mean that cocaine-induced vasculitis is happening more often than before. And exactly like you said, it's very difficult to be able to tell who uses cocaine and who doesn't. And obviously, yeah, detailed history is very important, but from earlier reports we noted self reported cocaine use is notoriously unreliable. And in the paper by Dr. Gill, they also clearly described that a large portion of the patients who denied using cocaine or said they had stopped using cocaine, that they still have positive urinalysis. So it's very difficult to know beforehand, and I think the only way to solve this is to to check the urine more often than we currently do.

David Liew  5:12 
And I guess it's probably compounded by the fact that levamisole, which is that anti-helminthic that's used to cut cocaine, which is thought to be a big part of inducing this vasculitis, doesn't show up on any of these screens as well. But it seems to be more commonly used nowadays in cutting cocaine.

Sander van Leuven  5:31 
Yeah, exactly. In the portions that are being confiscated by customs in the US and then in Europe, they see rising percentages of levamisole because it sounds like the ideal agent to cut the cocaine with because it's obviously a lot cheaper and it's supposed to enhance the effects by cocaine, and it doesn't show up in all the routine tests that we have to check for cocaine. So from the drug dealer perspective it sounds like an ideal agent to cut the cocaine with, but at the same time, it causes more problems because it can induce all these manifestations that we see in ANCA vasculitis.

If I could come back to what you said earlier, that it's difficult from a clinical perspective to make the diagnosis, I think one of the things that makes it harder is, is that what they did in Birmingham, they didn't just test for use of cocaine in urine, but all kinds of different drugs. And what they saw is that in a large portion of patients, they weren't just using cocaine, but they were also using other illicit drugs, with their own effects and manifestations. And that also makes the clinical course of the disease more difficult to recognise I think.

David Liew  6:45 
So I'd love to compare the work that you previously did when you were at Thomas and Guy's. Previously, when you were living in London, working in London, and compare that to this work now, which is from Birmingham and the Royal Free looking at how things have changed really. Would you care to compare the two series and how things might have changed in that time with levamisole-induced ANCA-associated vasculitis?

Sander van Leuven  7:14 
Absolutely. So, what we did we also looked retrospectively but one of the big differences already is that we looked back a little further - I think we looked back for a period of almost 15 years and we found 14 patients, and these two centres in London and Birmingham, they looked back for a period of five years; they found more than 40 patients, which is already a clear indication that this is happening more frequently now than it used to, and that we need to be more aware of that this is happening. Because in reality, it seems likely that we are now missing some of these diagnoses, because we are not testing for it. And like I said the manifestation can be quite variable, and I think in the recent paper by Dr Gill and colleagues, they saw predominantly patients who came through on an EMT pathway so they saw a lot of patients with midline destruction. And the case series that I did in London, together with my colleagues, we also saw a lot of systemic effects. So there may be a little bit of referral bias in there in the paper by Dr Gill in the sense that it's predominantly an ENT pathway and I think systemic manifestations of the cocaine-induced vasculitis are, in reality,  even a little bit more common.

David Liew  8:34 
So this obviously has some important therapeutic implications as well, because if you don't stop the cocaine, then the vasculitis keeps on going.

Sander van Leuven  8:44 
Yeah, and that's a big problem. I think, in a lot of these cases, they have been diagnosed previously as an ANCA-induced vasculitis. And when you look at the patients from the Birmingham clinic, they received a lot of heavy immunosuppressive therapy, including cyclophosphamide, rituximab... and all of that was ineffective on the background of ongoing cocaine use. So the mainstay of therapy, if you will, has to be that cocaine use is discontinued. The best therapy is just stopping cocaine use and I realise that's easier said than done if you are addicted to cocaine, but the downside, of course, is that you expose patients to all these heavy immunosuppressive agents with with the side effects that come along with it, without a chance of being affected.

David Liew  9:33 
So what do you think we should do in routine clinical care and then possibly, beyond that in research as far as addressing this issue is concerned? It seems really important to get the testing right, and to have a low burden of suspicion regarding cocaine use and possibly cocaine-induced vasculitis.

Sander van Leuven  9:50 
Yeah, I think it may be a little bit of an open door, but I think awareness is key. A problem with the fact that it can manifest in so many different ways is that patients can see different doctors. They can be referred to a dermatologist or a nephrologist, rheumatologist, an ENT specialist, and all of those specialists need to be aware of this presentation, that cocaine-induced vasculitis can closely mimic an ANCA-associated vasculitis and you have to be aware of that. The next step, obviously, would be to also screen for that by doing urinalysis. And I think, like I said before, a very important message from the paper by Dr Gill and colleagues, is that we need to apply urinalysis more often than we currently do. Because as cocaine-induced vasculitis... cocaine use in general is increasing but cocaine-induced vasculitis is also increasingly prevalent. And we're not going to find what we're not looking for. So we need to do more urine tests to come to this diagnosis sooner, preferably before patients use all this immunosuppressive therapy. With regard to research, I think that's a very important issue and as it often is, it's also a difficult issue because we know that it's happening more often than we diagnose. So it's under diagnosed. And the only way to solve that really is to look for it more often. And like I said, the paper from Dr Gill clearly shows the best way to do this is just do urinalysis, and I think the vast majority of these patients will do urinalysis anyway, because we want to check for renal involvement. But the thing is, we also need to look at use of cocaine. So I think we need to do that more often in clinics across the country, to get a better feel of how often this actually occurs. And there have been some reports on the use of a different type of antibodies, the anti-human elastase antibodies, which can give you a little bit more information when you try to discriminate between ANCA-associated vasculitis or cocaine-associated vasculitis. But the downside really is that those assays are not commonly available, so it is going to be difficult to use in the clinical setting.

David Liew  12:09 
Well, I think there's a lot for us to work on there, but a lot for us to think about how we can do things better in the future. Thank you so much for joining us today, Dr van Leuven.

Sander van Leuven  12:16 
Absolutely. Thank you for having me.

David Liew  12:18 
And for that whole editorial, for the article behind it, and plenty more head on down to Rheumatology Advances in Practice. Everything's open access and there's some excellent content there. Thank you.

Voiceover  12:30 
Thank you for listening to Talking Rheumatology Research, brought to you by BSR. Please do rate, share and subscribe through your favourite podcast app.