Q&A Session – SarcoidosisUK Neurosarcoidosis Patient Day 2023

Transcript 

Leo Casimo: I think we’ll get started again. So for speakers, when they’re available, could unmute themselves and turn their videos on. Unfortunately, Dr. Peter Fernandes has had to leave a little early as he had another commitment. I believe the rest of the speakers are here, so that’s great. 

And before I go into the questions that have been submitted, I just wanted to read something out from the Q&A box. It’s not actually a question. It says, “This is just a comment. I’m a doctor who happens to have cancer and Sarcoidosis and I cannot overemphasize how good these presentations have been. They have, I think, been pitched perfectly for the audience. The presenters have managed to present a good chunk of information in a concise and accessible manner. I’m happily very impressed, considering that we don’t even know the cause”. 

And I think a lot of people who are watching along will be feeling that today as well. So thank you so much for your presentation so far. These events are really invaluable to the Sarcoidosis community, so it means a lot to us to have you all here.

 And before we start asking the questions that have come in, a couple of things. Obviously this is an information event. We don’t have access to your medical history or records, so we can’t provide sort of personalized medical advice, of course. We will, of course, have a discussion about the questions that have come in, but please do speak to your own doctor for personal medical advice. 

I initially tried to group the questions into different categories, but it’s been quite a challenge with the new ones that have come in. So it may just be a question of asking the ones in the order that they’ve come in. So I think the best way to do this, I’ll just ask a question. I won’t direct it to anyone, but if anybody’s happy to answer, if they just answer, and then we can kind of add on as we go. 

So this question has come in from Susan and they’ve asked, at what point does Sarcoidosis become Neurosarcoidosis? I was diagnosed in 2001 with Sarcoidosis, but it developed to peripheral neuropathy in both my limbs and into my skin. Is this now Neurosarcoidosis?

Dr. Victoria Singh-Curry: I start with that. So if you have a definitive diagnosis of Sarcoidosis in that it’s been biopsy proven from tissue elsewhere and you’ve got a confirmed neuropathy and no other cause for that neuropathy has been found, then I guess we would say that you have probable Neurosarcoidosis.

Leo Casimo: Thank you very much. I’ll move on to some questions to do with symptoms. So this person has spoken about problems they’re having within the oral cavity. Things like soreness, stinging, tingling, pain in the face. They said the consultation with their professor of oral medicine resulted in a diagnosis of probable oral sarcoid, but he also believes the symptoms are nerve related and neurosarcoidosis could be the cause. Any advice would be appreciated. Could those kind of symptoms be related to Neurosarcoidosis?

Dr. Victoria Singh-Curry: It could be due to cranial nerve involvement with Sarcoidosis. So it’s certainly possible. And so I think it would be advisable for you to be referred to a neurologist for assessment and investigations.

Leo Casimo: Thank you very much. Great. It is possible. Thank you. On referrals to neurologists, somebody has asked I can’t find it in the Q&A box right now, but they’ve asked, if everybody who has a Neurosarcoidosis diagnosis should be seen by a Neurosarcoidosis expert, what advice could we give to that person?

Dr. Victoria Singh-Curry: It would be preferable for them to be seen by someone who has experience in seeing patients with Neurosarcoidosis, and that may be because they need to escalate their treatment in order to get adequate control of the disease. And these are drugs which, as we’ve heard, do come with risks and potential complications. And so it’s important that the person that’s directing your treatment has experience of them.

Leo Casimo: Thank you very much.

Dr. Victoria Singh-Curry: I know that it’s difficult at the moment.

Leo Casimo: Okay, we’ve had another question on symptoms. This one quite worrying. They said they were cooking, and after a while they realized their arm had been resting on the pan. They moved it away and their arm was bent, but they didn’t feel it as it was happening. Is this something that can happen when Neurosarcoidosis? And does it have a name?

Dr. Victoria Singh-Curry: Yeah, definitely. I guess it’s sounding most in keeping with a neuropathy, and so that would need to be looked for. But other issues with how the brain is functioning and the spinal cord is functioning could potentially explain that. So, yes, it sounds like that person does need to see a neurologist and be thoroughly assessed and investigated.

Leo Casimo: Thank you, Dr. Singh-Curry, another symptom question, this time about teeth. This person has always had perfect teeth, but now they’re having a lot of problems. It seems like the teeth end up breaking and they’ve become very self-conscious about this, and the teeth are falling apart. The dentist says it could be from the medicine they take, and they want to know, is this related to Sarcoidosis or their medicine, or could it be something else? And can this happen with Neurosarcoidosis?

Dr. Victoria Singh-Curry: I don’t think that’s caused by Neurosarcoidosis itself, but it is probably a complication of the treatment that they’ve received. So, steroids, but also some of the medications which are used to protect bones from steroids can lead to dental issues.

Leo Casimo: Next one is about slow commands. So somebody said my right side is very slow to command. For example, if I command my leg to go up the stairs, it will, but it takes quite a while for that to happen. Again, could this be related to their Neurosarcoidosis, and should they see a neurologist about this?

Dr. Victoria Singh-Curry: Yeah, definitely. It could be due to inflammation in the brain or the spinal cord that’s causing those symptoms. And so, yes, again, I think they need to see neurologist. 

Leo Casimo: Thank you. And next question. It’s actually something that comes up a lot. It’s a question we get asked quite a bit at these events. So they’re saying their head, neck and spine MRI showed no active Sarcoidosis and no changes from the previous year, but they’re having a lot of neurological symptoms and I know this has been touched on, what advice could we give to this person?

Dr. Victoria Singh-Curry: So, again, I hope that they’re seeing a neurologist and that their Sarcoidosis and Neurosarcoidosis is being treated appropriately because it’s good that their scans are stable. But sometimes when there’s damage to the nervous system, even though there may no longer be any active inflammation or new inflammation, those areas of previous damage can continue to cause symptoms. And as we touched on as well, you can’t look at one part of yourself in isolation, you have to take everything into occur which is why the multi-disciplinary team is so important and so psychological health what’s going, you know, in the on in the environment around you can also impact your experience of symptoms and so all of these things need to be addressed together.

Leo Casimo: Thank you very much yes it is extremely important. I have a look at some of the ones that came in through the live chat because I don’t want to just focus on the ones that came in in advance. A lady called Donna has written in saying they’re 68 years old and has had Neurosarcoidosis for over 10 years. They’ve had problems with weaknesses numbness of legs balance problem. 

They’ve been stable on Methotrexate and infliximab them up for the last seven years with no side effects and she’s been discussing with her specialists whether she might be in remission and could slowly wean off the medication, especially in view of aging and being on immunosuppressants. They doctors feel that it is her decision as there are there isn’t many studies to guide this just any comments they said would be really appreciated and maybe some things to consider.

Dr. Tarunya Arun: Yeah, I mean, I can take that one if you wish. The most important thing, I guess, is to think about when you start treatment. As the person who’s just asked the questions rightly said, there’s no dictates to when we can withdraw treatment, we know when to start treatment. But taking people off treatment, whether it’s the Oculus or MS or whatever, the condition is a little bit more tricky. 

What I would say is that any withdrawal of treatment needs to be sort of thought about in the context of a number of things, how long the person has been stable for. So it looks like the lady here has been stable for a little while. It also needs to be in the context of withdrawing treatment gradually with close monitoring. So one thing to say is that monitoring people who come off treatment is really important. 

So one of the concerns which people raise is coming off treatment means they don’t actually have a follow up appointment. So what I would say is that if the lady is on both those treatments, it would perhaps need to come out stepwise. There needs to be more frequent follow up arrangements with their neurologist or neuropsychologist specialist as they’re coming off treatment because it’s really important. 

And then whatever the disease condition was for which they were started on it, whether it was sort of radiology or clinical examinations or whatever, that needs to sort of carry on for a little while after they’ve come off treatment. And I generally tend to keep people on what we call surveillance scans and clinical reviews, just as I would do with treatment for at least a couple of years after they’ve come off treatment. And I think that’s really important to say. 

So yes, I think treatments are never lifelong. That’s essentially important to think about equally in the context of something like infliximab the limited data we’ve got essentially says that people can relapse when we are taking people off infliximab. So really important to think about keeping an eye on things. I hope that answers that question.

Leo Casimo: Thank you very much. So follow ups are very, very important here. And while we’re on infliximab, we’ve had another question asking what is the current position on prescribing infliximab in UK hospitals?

Dr. Tarunya Arun: Yeah, as Dr. Rice pointed out in the talk, I think we’ve got current license by NHS England in a very limited way to prescribe infliximab that’s for people who’ve got what we would describe as refractory Sarcoidosis. That is defined by people who failed previous treatment with one of the immunosuppressive treatments, which is what I highlight in my talk, like Methotrexate is a disprin or mycophenolate and they needed to have sort of been on it. Failed that treatment, either by view of the fact that they’ve either got significant side effects or actually failed it because their disease hasn’t well, controlled. 

And currently the license is only for central nervous system Sarcoidosis. So, for example, for peripheral nerve Sarcoidosis, it would need us to apply in a very special way that wouldn’t be kind of licensed by NHS England, so it’s got a restrictive license. The other important thing to say is that patients such as that have to be discussed at a specialist MDT, which again highlights some of the need for us actually having those specialist MDTs in place where we actually make these decisions on treatment.

Leo Casimo: Thank you very much. Bay has written in saying thank you for a really informative event. I’ve been diagnosed by ebus with pulmonary SARC. I was also referred to a neurologist because the pulmonary Sarcoidosis did not explain the majority of my symptoms. The neurologist got to the point of probable Neurosarcoidosis, but has now backtracked because my latest lung scans show good improvement in my lungs. Does this logic track? Does pulmonary involvement suggest that my neuro symptoms are not caused by Neurosarcoidosis?

Dr. Victoria Singh-Curry: It is a tricky one. Without having access to all of the relevant information, it sounds like the diagnosis of Pulmonary Sarcoidosis is secure. Even if the Pulmonary Sarcoidosis is well controlled or quiescent, it doesn’t mean that it cannot be active elsewhere. And so if there are abnormalities on the scans which correlate with the symptoms, then I would say that the diagnosis of probable Neurosarcoidosis would still stand, but we would need the full information in order to comment accurately.

Leo Casimo: Yeah. Thank you very much. Some other questions going back to treatment. Somebody’s asked, and I know this was talked on in one of the talks, but if we could just go over it again. If infliximab treatment fails, what treatment options come next?

Dr. Tarunya Arun: Yeah, so it’s not a completely uncommon scenario. In some of our specialist clinics, the numbers are small because infliximab, as you saw, is a very strong treatment and majority of patients, I’ll probably say, provided it’s given in the way it should be given, we’re checking for things like antibodies on a regular basis, making sure people are having enough infliximab. So we often measure infliximab trough levels in our infliximab suite.

So essentially, just to make sure people are getting enough infliximab. And once you’ve made sure that all those things are true. The other thing to point out is people often do well with infliximab with a second immunosuppressive agent rather than it being on its own. So provided all those caveats have been sort of ticked off, then there are other options. We talked about both myself and Dr. Rice, both of us talked about other treatments in the future. 

So we have a significant minority of patients. We’ve escalated to things like the IL-6 treatment with Tocilizumab, for example, or the Jackson-2 inhibitors. But that needs to be a very special application to NHS England for them to be able to approve it, so it’s not easily available. Equally, that also highlights some of the important things we have to say about multidisciplinary working. So many people have multi system involvement, so Neurosarcoidosis or pulmonary or rheumatological involvement in some of our patients, not only has their Neurosarcoidosis got worse, but also their rheumatological diseases got worse. And the way we’ve been able to access treatments is by liaison with the rheumatologist. 

So hence that conversation with your other consultants is really important. So simple answers, it’s difficult not saying it’s really easy for people or refractory to infliximab, but then there are other options available and hopefully the next decade we’ll see more grow such.

Leo Casimo: Thank you very much. Next one is another question that we do get quite a lot actually, which is about lifestyle and whether there’s any sort of recommended diets or lifestyle changes that people with Neurosarcoidosis should make. Is there anything specific we can say or is it just aiming to follow a healthy lifestyle in every way they can in terms of exercise and diet?

Dr. Tarunya Arun: Claire could do that.

Dr. Claire Rice: Thank you. I think that’s something that we’ve really neglected kind of as a worldwide medical body is the importance of lifestyle measures and in particular exercise for cardiovascular fitness. And that’s often very difficult where patients may have neurological disability. But trying a couple of times a week to actually get sweaty to get your heart rate up into a cardiovascular zone has enormous benefits for brain health generally. 

Some of that is what we used to kind of think of as normal brain aging, rather than having a specific effect necessarily on Neurosarcoidosis. But clearly if you have one problem that can already affect or has the potential to affect the brain, then the last thing you want is another. So I think there are very definite benefits, wherever possible, to good cardiovascular exercise a couple of times a week.

With specific reference to diet, I’m not aware of any proven effects on diet. I think there are good reason to check things like calcium levels, vitamin D levels, very specific vitamin D measurements that aren’t necessarily routinely done, so 125 dihydroxy vitamin D, for example, in patients who have Sarcoidosis. And there may be interventions that are required if those are outside normal range. But beyond that, I think a good, healthy, broad based diet, slight Mediterranean flavour. I think that would be our usual advice. And really that’s because of its proven effects on cardiovascular risk factors rather than specifically Neurosarcoidosis.

Leo Casimo: Thank you very much, Dr. Rice. Had a few questions on that. I think you’ve covered that well. So we’ll skip past those. A few questions about remission. So somebody’s asked well, there’s a few. I’ll read both out because I think we can answer both at the same time. Somebody said, have the doctors seen a remission in the disease with people with Neurosarcoidosis? I think they’re asking, can it go into remission? And somebody else has asked, how does a doctor of the patient know when they are in remission? If in remission, will scans still show a lot of inflammation in the brain? And if you feel like you are in remission, but brain scans say otherwise, how do we know if a patient is in remission or not?

Dr. Tarunya Arun: I think it’s very difficult to define remission. I think we treat other inflammatory conditions. Remission is a little more easily defined than a Neurosarcoidosis because people are intensely symptomatic even following their normal scan and other things. 

So if remission is defined, say by as a person’s just asked, the scans can be normal still. They’ve got symptoms. The important thing to say that people can have residual symptoms even after what we say their active disease is controlled. So all the treatments that I highlighted and all the treatments which we think are coming out in the future are not going to perhaps do a fantastic job in getting rid of all the symptoms. 

So if remission is defined by that, then that’s a little bit different. But in terms of clinician being able to assess remission to some extent, that’s where I guess it’s really important to build that expertise within kind of, you know, because sometimes remission defined by non-experts and not necessarily people in remission, but actually that’s really important. 

The other thing to say is, going back to what I said earlier, I think the monitoring is really crucial as well, to keep an eye on how people progress through what we think is a remission situation and journey. 

And the third thing is a lot of symptoms are often reflective. So neurological symptoms doesn’t necessarily mean Neurosarcoidosis. So neurological symptoms can also mean their systemic sarcoid is not very well controlled. So neurological manifestations of systemic disease also has to be taken into consideration. 

So if your pulmonary sarcoid is playing up, or if you’ve got cardiac Sarcoidosis, people often present with headaches or lethargy or cognitive impairment or mood problems. And whilst those can be because of neurological Sarcoidosis, but it could also be because they’ve got systemic disease which is poorly controlled. So no straight answer to that one, Leo.

Leo Casimo: Thank you very much. Okay, next one is not a question we get very often, actually, but I think it’s an interesting one. What is known about paediatric neurosarcoidosis? What are the differences and challenges in diagnosis between children and adults? And does the disease progress differently in children? I understand that it’s quite rare, isn’t it? Would anyone be able to provide some information on that?

Dr. Victoria Singh-Curry: I think it’s difficult for us to comment, really, because we’re all adult neurologists, so we don’t really have any experience of dealing with paediatric patients at all. I don’t know if Tarunya or Claire have any clues.

Dr. Tarunya Arun: I mean, yeah, the only thing to say I completely echo what Victoria says. I think the paediatric population have got a different I mean, the outcomes are different even for other kind know, drawing comparisons to other neuroinflammatory conditions, but this is not a standard neuroinflammatory condition, it’s a systemic condition. 

So I think the management will differ because the way in which children respond to treatment is very different and actually the outcomes are different in patients. So I think the simple answer is that I don’t think it’s been studied enough, number one. Secondly, we probably don’t have the expertise to answer that question in complete honesty in what we want to do, but hopefully once we know a bit more about the condition Peter was talking about kind of a number of pathophysiology genetics, we’ll probably then be able to identify that kind of trajectory.

Leo Casimo: Thank you. We do also, if anybody is interested in learning about Sarcoidosis in children, again, it is very rare. A couple of years ago, Sarcoidosis UK did a Q&A with a children’s doctor about Sarcoidosis in children. So it might be worth giving that a watch if you are interested. Someone’s asked about cranial nerve involvement. What are the most common symptoms and what treatments would support this?

Dr. Victoria Singh-Curry: I guess in the context of Sarcoidosis, it’s spatial nerve palsies, which are probably the most common, but it can affect any of the cranial nerves. So the nerves so the optic nerve that mediates vision, the nerves which control the eye movements, the nerves that supply sensation to the face that control swallowing and the muscles in terms of talking and the approach is the same as we’ve discussed in the presentations. It’s a thorough clinical assessment followed by scans, MRI scans with contrast. 

I guess in the context of cranial nerve palsies, it’s important to think about doing the finer cuts through the base of the skull as well, because inflammation in those nerves may be missed on just a straightforward MRI head. And then in the context of treatment wise, it’s the whole patient in perspective. So how much are they disabled by it? So if it’s optic neuritis or they’ve got to pull vision, then the approach is slightly different to managing a facial palsy and may require more treatment than the facial palsy.

Leo Casimo: Thank you. Somebody’s asked, do symptoms of Sarcoidosis or Neurosarcoidosis usually get worse as you get older? I’m 36 and the changes over the past four to five months have been challenging. Only just started this treatment this week they’re just curious if the symptoms tend to get worse with age.

Dr. Victoria Singh-Curry: Hopefully, once you’re established on treatment, things will start to improve. But with any neurological condition that produces a deficit, you also have to factor in other things happening to you as you age and the aging process itself. So symptoms can become a bit more prominent as you age, just as part of that aging process. If that answers the question fully.

Leo Casimo: Yeah, it does. Thank you. Paul’s written in and he said, what do today’s specialists on the panel think about patients making a probable self-diagnosis of Neurosarcoidosis? I think the advice here would be to see a specialist, right?

Dr. Victoria Singh-Curry: Yeah, definitely. As I spoke about as well, if you’ve got an established diagnosis of Sarcoidosis and you’re on treatment, then neurological symptoms could be a side effect of that treatment which will need to be addressed and nothing can be taken in isolation.

Leo Casimo: Thank you. Tom’s asked what is considered a high dose of steroids?

Dr. Tarunya Arun: Yeah. So we’ve got to, again, to draw parallel from what we know from other conditions, so there isn’t a diktat with regards to that if you consider the Rheumatological society. So anything sort of over. So they define low, medium and high dose steroids. So anything over 40 milligrams of prednisolone would essentially equal to high dose steroids. 

As neurologists, we use up to 100 milligrams of steroids, probably a bit more in not only Sarcoidosis but other neurological conditions. I think that’s a very subjective sort of range for something like Sarcoidosis, where we don’t have it defined, but really drawing parallels from other rheumatological conditions. Depending on where you look, 30 or 40 milligrams would essentially be high dose steroids, needs monitoring.

Leo Casimo: Let’s see. So somebody has written in. They’ve said some people refer to Sarcoidosis not as an autoimmune condition, but an overactive immune condition. They would like to understand the difference in between these two terms, if there is one.

Dr. Claire Rice: I think the way I would think about that is that more that the immune system is misdirected rather than necessarily over or underactive. So we need our immune system to fight infection and also as a surveillance function to look for malignant cells, for example. And clearly it’s not 100% accurate all the time. 

So people who don’t have drugs and medication to suppress their immune systems still can be susceptible to infection and can still get cancer. But those are the two very major functions of the immune system. And in autoimmune disease, there’s a persistent activation of the immune system that is inappropriate. 

So it is persistently activated in a very specific direction. So the direction or the target of that over activation might be the pancreas and diabetes, for instance, or the joints in rheumatoid arthritis, for instance. And in Sarcoidosis, we don’t really know quite where that it is not organ specific, that target, but there is an activation. 

The immune system is really doing what it’s programmed to do. So it’s not, in a sense, being either overactive or underactive. It’s just being stimulated inappropriately. And many of the drugs that we have available at the moment are essentially a bit of a blunderbuss process to dampen that immune system response and to try and switch it off without hopefully making the patient too vulnerable to either infection or malignancy. 

And the hope is that with our ever more specific immune treatments that we can target the bit that’s malfunctioning more specifically. So instead of dampening the whole of the immune system, we’re actually looking at the very particular cells or the very particular pathway that in each of these different autoimmune conditions is malfunctioning and targeting that specifically. 

And that’s hopefully where we can be much cleverer about our treatments in future, more specific about our treatments in future, and therefore, hopefully get the best results in terms of disease suppression, but also in terms of side effects.

Leo Casimo: Thank you. Dr. Rice. We’ve probably got time for maybe one or two more. Somebody’s asked about well, I think they’re on cancer treatment. They’ve asked about any information regarding on the effect of radiotherapy on the development of Sarcoidosis. Is anything known about that that we’re aware of?

Dr. Tarunya Arun: Came my colleague – Yeah, Claire will go with it.

Dr. Claire Rice: So I was actually going to ask you to repeat the question. Sorry. 

Leo Casimo: Somebody asking if anything is known about a relationship between radiotherapy for cancer treatment and the development of Sarcoidosis or Neurosarcoidosis?

Dr. Claire Rice: I’m not aware of specific links. There are definite links with certain treatments. Radiotherapy, you can get granuloma formation as a generic injury response within the body, but I’m not aware of it triggering kind of a multi system disorder.

Dr. Tarunya Arun: It’s the question about whether reacted therapy can be used as a treatment, Leo, or does it cause Sarcoidosis?

Leo Casimo: It was more about can it cause Sarcoidosis? Okay, I think we’ve spoken enough about lifestyle. Someone’s asked about pain management. If somebody’s really struggling with pain, is there a recommended approach to pain management?

Dr. Claire Rice: I think there are a number of different levels. I think, first of all, trying to work out what the cause of the pain is. Is it due to neuropathy, for instance, which can certainly be painful? Is it a side effect of treatment, and is it Neurosarcoid that’s causing it? So I think making sure the diagnosis is correct, not just because of the systemic disorder, but actually specifically the pain. If we are attributing pain to neuropathy, secondary to Neurosarcoidosis, we do have a range of medication to try and help that. 

A lot of those treatments were initially designed for other things. Some of them were antidepressants, some of them were anti-epilepsy treatments. But they do act upon the nervous system to not necessarily make those sensations normal, but to dampen down how intrusive they are, so how much they interfere with people’s day to day life and in particular, their sleep. 

So, yes, there are a range of different medications. I’m sure the names will be familiar to many people on the call. Things like Amitriptyline, Nortriptyline, Duloxetine, Carbamazepine, Gabapentin, Pregabalin, Lacosamide. Lots and lots of them. They do all potentially have significant side effects because they do act on the central nervous system, most particularly somnolence. But other specific ones, dry mouth with amitriptyline, for instance, gabapentin can make people feel a bit seasick or have a sensation of disequilibrium or feel a bit confused. 

So they need to be monitored, they need to be used carefully and judiciously. General practitioners would have quite a bit of experience with that. Neurologists would certainly have experience in using those kind of medications. And obviously when we get stuck, we refer to specialist pain clinics from time to time as well. 

But I guess the main thing is to make sure that it’s not a side effect of treatment, say, diabetic neuropathy that has been induced by treatment, for instance, or that it’s not a sign that the Neurosarcoidosis is inadequately controlled and that the disease process itself needs better treatment.

Leo Casimo: Okay, thank you very much. I think we’ll just do one more one come in. A couple of minutes ago from Michael, he’s asked I’d be interested to know the answer to actually, is it true that Sarcoidosis and neurosarcoidosis can target weaker parts of your body? I previous trauma to areas from injury. Is anything known about this?

Dr. Victoria Singh-Curry: I suppose, thinking about the spinal cord itself, it’s not uncommon to have an area of inflammation, perhaps due to Neurosarcoidosis at the site of where there is some compression by an intervertebral disc and things like that. So in that respect, yes. I’m not certain about anything else beyond that, though. I don’t know if Tarunya or Claire, but certainly in the spinal cord and compressive lesions, they can be more prone to develop inflammation there as well, unrelated to that compression.

Dr. Tarunya Arun: Yeah, no, absolutely. So obviously granulomas are just to kind of add yes, I’m not aware of it either, but in terms of granulomas can obviously form at sites of not necessarily non caseating granulomas. So really important because sometimes in pathological reports of other surgeries, granulomas are reported and hence the surgeons do send us a request saying, does this person have Sarcoidosis? But very often it’s very much an injury response and not necessarily a Sarcoidosis granuloma which forms it. So pathologically there is a distinction, but clinically I’m not aware, actually, apart from what Victoria just mentioned.

Leo Casimo: Okay, thank you very much. I think, unfortunately, we’re going to have to draw the Q&A to a close there. Thank you so much to everyone who sent in questions and thank you to the speakers for being so great answering everyone’s questions and for being here all day, really. It has been such a fantastic event and we really do appreciate giving up your time and your very busy schedules. And if you do have a chance, before you leave, please do have a read through the chat box. It’s really quite clear how helpful people have found this today. So we really are grateful to all of you for being here. Thank you very much!