BONUS CASE: Muscle weakness

In this bonus case based episode Steph Gall from the BSR digital learning board discusses an interesting case of muscle weakness with Dr Lisa Waters a Consultant in Rheumatology and Acute Medicine from Manchester. Can you work out what's going on? 

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Transcript

 GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   
 Hi, My name is Stephanie Gall and I'm delighted to be joined by Doctor Lisa Waters, a consultant rheumatologist at Manchester Foundation Trust. Thank you for joining us today, Lisa.
Waters Lisa (R0A) Manchester University NHS FT   0:21
 Thanks very much for having me. It's a pleasure to be here. So I will start with the case that we've got. So I've renamed the patient Ian and there's a few bits in his history that I have changed, but it gives the overall picture of this patient that we see in our rheumatology service. So when he presented to me, he was a 60 year old male who had a history of COPD. He'd been a lifelong smoker, had some coronary artery stents fitted and he also had a history of hypertension, hypertension and he was referred to my clinic as a new patient by the GP with a history of joint pain, a vasculitic rash and he's been found to be ANA and FSA positive on blood tests. So I met Ian in the clinic and his main concern was of a two year history of weakness and pain in the left knee. And this had progressed over the last six months. He described a kind of locking of the left knee without stiffness or swelling and he described to me how it had become difficult to stand from a seated position and that stairs were particularly difficult.
 Helpfully he'd already had an MRI of his left knee, which had shown mild degenerative change only.
 He also reported that over the last six months he developed a rash that was intermittent and red, typically affecting both his feet and then the lower legs. Unfortunately, he doesn't have a smartphone, so he didn't have any photos to show me. Importantly, he did describe in the last five years that he'd noticed biphasic colour changes in his hands and feet with associated numbness in response to cold temperatures. He reported weight loss of approximately 3 stone over the last 12 months, but there were no other symptoms suggestive of connective tissue disease, such as thicker symptoms, mucosal ulceration, seraphitis, or scarring alopecia.
 Ian had worked as a kitchen fitter but was unable to do this job due to his current symptoms, and he lived with his partner, continued to smoke and had an alcohol intake at approximately 37 units per week. When we examined Ian clinic, his weight was 84 kilogrammes with a normal blood pressure and urinalysis was negative for blood and protein. All peripheral pulses were palpable, and there was no digital ulceration or skin thickening chest was clear to auscultation abdomen softer, non tender and there was no organomegaly felt heart sounds were normal. There was evidence of left quadriceps wasting and there was no fasciculations noted in the limbs. Knee examination revealed reduced flexion on the left side compared to the right, but this was mild. There was no effusion and hip examination examined normally. Power in knee flexion was four out of five, but otherwise the neurological examination in the upper and lower limbs was normal. There was no evidence of a vasculitic rash, and there was no synovitis to any other joints. So looking back from my clinic letter at that time, I explained that there were some features of a connective tissue disease with the new one set of colour changes in the hands, the rash and the ANA positivity, but I explained to Ian that I wasn't clear completely what the diagnosis was at this point and that we would arrange some further testing, including immunological blood tests and that given he had weight loss and was a significant smoker, that we would need to investigate further. And of course, I was thinking about malignancy at that time. I also referred to him for physiotherapy input and I asked Ian if he could get some photos on somebody else's phone of the rash that would be helpful when I next reviewed him. So, to talk through the kind of important blood test is the count was normal, Lfts were normal and renal function was normal. His CRP was normal and ESR was mildly elevated at 18, CK surprisingly, and I was surprised when this came through was raised at 771 compliment four was low with a normal C3 but double stranded DNA was normal and of course the FSA came back as positive on that testing, which previously been done by the GP.
 So I remember being a bit surprised about the CK being raised and I went on to arrange MRI of the thighs and this was reported as showing that bilateral muscle edema with a subtle impression of muscle atrophy. And the radiologist reported that the findings were consistent with myositis. I'd arranged the CT chest, abdomen and pelvis, and that showed a lung nodule for which we referred to our respiratory physicians and they felt that that was a stable lung nodule that didn't need any further input.
 So following the findings of the MRI, I went on to arrange a muscle biopsy.
 And that was consistent with myositis, the histology report said that there was myopathic features with significant myositis and prominent muscle atrophy compatible with the clinical presentation. And they also spoke about NHC1UP regulation on complement deposition, supporting the immune mechanism behind the phenotype of myositis. In addition to that, we went on to do nerve conduction studies and that was reported to show patchy, myosytic changes with sensory polyneuropathy with predominantly axonal features, with a possible motor component.
 So I was feeling that at this point that Ian had a diagnosis of an idiopathic inflammatory myopathy, and I think that was reasonable based on the investigations that I had to hand. I think by that time his myositis specific antibodies had come back and these were all negative. So based on that diagnosis, I commenced him on Prednisolone. I think it was 40 milligrammes once daily at the time, and we arranged for him to be educated on Mycophenolate mofratil. I reviewed him three months later and Ian explained that he was no better, but not really any worse. He had had to stop fully working at this point and actually he hadn’t started the Mycophenolate and I think that was due to his one of his parents dying at that time. So he hadn’t felt in the position to start it. He then also reported to me that he had a few month history of dysphagia and clinically he examined how he had done the first time I met him and by this time on repeat testing his CK was normal. So we carried on the treatment and I arranged a barium swallow and again I can remember where I was when this came through because I was about to go on two weeks annual leave last summer and this barium swallow came into my in basket and it showed evidence of aspiration and also of oesophageal dismotility. And so clearly this was a phone call to Ian arranging for him to come in via the acute medical take for IV Methylprednisolone and so speaking to both acute medical colleagues and rheumatology colleagues I handed him over and he was admitted to a General Medical ward, and I think it's important to say at that point again, his CRP was normal, hiss CK was normal by this time, and he had a chest X-ray, which was which showed features in keeping with chronic aspiration.
 So at that point, the diagnosis was of a myositis related dysphagia and he was treated with IV methylprednisolone and a repeat MMT 8 Score was performed at that point and again there was proximal weakness only and we're really fortunate where I work that we have a weekly rheumatology MDT which I know a lot of units do have and I think it's a really important touching point for discussing cases like this.
 And again, he was discussed with consultant colleagues and they saw him and you know this myositis diagnosis continued and could there be a Sjogren's overlap with the peripheral sensory neuropathy.
 Three weeks into the admission, when it was quite clear that he wasn't responding to high dose Prednisolone, one of my consultant colleagues suggested that we review the initial biopsy and also aspirin neurology opinion. And I think I returned from leave the following week and it was really helpful to actually have that MDT with the histopathologist and the neurologist. And I think at that point we were reviewing the diagnosis and we told Ian that this was the case and that was due to the lack of improvement in the treatment that we've given. So the biopsy was looked at again and some further staining was arranged and sent off to our tertiary centre, which is Salford to have a look at that again, and I think we decided as a team that whether this was a new autoimmune related or not, he needed to have a peg inserted and so he went on to have that. He was eventually discharged I think he was in for about 8 weeks in total. And I think at that point it's fair to say that there was still ongoing diagnostic uncertainty whether this was an inflammatory myositis or more typical of inclusion body myositis. When he was reviewed late into his admission, he had developed some subtle hand weakness and that hadn't been picked up before.
 He was eventually seen in Salford by a tertiary neurologist with a special interest in inclusion body myositis and the feeling at the moment is that he has probable inclusion body myositis and actually I saw Ian last week in clinic and we have started weaning the Prednisolone and stopped the mycophenolate on the basis of that review.
 
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   10:29
 So that's a really interesting case and I would have been surprised myself with a CK coming back as that high. What were your initial thoughts that it could be? I know you mentioned connective tissue disease and he mentioned that he had this intermittent vasculitic rash.
Waters Lisa (R0A) Manchester University NHS FT   
 Yeah. So I think at that point, you know, I was kind of thinking, is this a new onset of connective tissue disease and perhaps the left knee weakness, which wasn't particularly weak, was new and you know, was that part of a kind of osteoarthritis that you had mild osteoarthritis in that knee? I think I was surprised and I think probably one of the learning points looking back from this is that even though the CK was raised at 700, it wasn't quite at the level that we would expect from a typical kind of demento or polymyositis that we're looking at that we will be used to looking after in rheumatology services.
 So I think at that point I was kind of keeping an open mind, to be honest and I think malignancy was still on my mind you know, this was slightly unusual. He'd lost weight and he was a lifelong smoker, so I think I wasn't rushing in to make a diagnosis initially after the first appointment. But then as the things came together, you know, the kind of myositis on the MR and then it was kind of confirmed on the biopsy you know, I think I was going down the route of this being a polymyositis picture that we would aim to immunosuppress.
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   12:00
 Yeah and you said his  CK normalised was that after the steroids or did it sort of normalise prior to the steroids?
Waters Lisa (R0A) Manchester University NHS FT   
 So it normalised after the steroid therapy and with the oral prednisolone.
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   12:15
 OK. And I know you mentioned sort of because he wasn't improving with the steroids while he was in hospital. What point did you think, oh, actually maybe this is something else is going on?
Waters Lisa (R0A) Manchester University NHS FT   12:29
 Yeah. So I think it was about six weeks into his admission where, you know, we've discussed him several times in the MDT, the rheumatology, MDT that we have for inpatient and I think we just started to think, you know, this is not responding in the way that we would think it should do and you know, I think we all learn in our rheumatology training about inclusion body myositis kind of been there in the differential but I have to say this is the first time I've actually come across one and yeah, so I think it was that lack of response to normal treatment because really, you know with IV methylprednisolone you know you would expect to see some improvement in in symptoms with that and so it was that lack of response really that made that prompted it.
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   13:11
 Yeah. Yeah. And it's interesting that you ask the histopathologist to relook at the muscle biopsy because it's not, we tend to sort of, or at least we tend to accept what it says on the muscle biopsy and how easy was that to get somebody to re look at it?
Waters Lisa (R0A) Manchester University NHS FT   13:34
 Yeah, I think we're quite fortunate. I think we have good relationships with the histopathologists here where I work at for sure but again, you know that's a learning point, isn't it? They go on the information that we give them. And so I think you know, again, when I come across this it, you know it will be perhaps I'll be a bit more specific in the information that I have and certainly you know that the CK wasn't that high looking back. So I think you know, it was easy to do and I'm really grateful for that but I think it is dependent on what we explain to them as well, isn't it in that sense?
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   14:11
 And the muscle biopsy that was taken, I know the sort of the logistics in different departments of actually getting a muscle biopsy is quite difficult. Who was it who performed the muscle biopsy for you?
Waters Lisa (R0A) Manchester University NHS FT   14:23
 So we have plastics that do it and I'm pretty sure, Steph that our Plastics team did this for us. So that would be our usual route and again, I think we have a good relationship with them and I've never found that to be difficult but I think certainly having rotated on the training, I know that that isn't always the case that in many.

 GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   
 So I know for this case it's very complex and there were multiple people involved in this case. At what point did somebody actually think of inclusion body myositis?
Waters Lisa (R0A) Manchester University NHS FT   
 I think it was about that six, six week mark into his admission with the lack of response to Prednisolone that one, well, kind of we discussed as an MDT you know, is there something else going on here? And I guess with the demographic that Ian is, you know 60 year old male you know inclusion body myositis would be up there, wouldn't it with your differential of these patients, I think the slight complexity for him was that his pattern of muscle involvement certainly for us as rheumatologists was never the typical kind of, you know finger flexes or, you know, the feet are often involved I understand an inclusion body myositis. So I think that made it more challenging but yeah, I think it  also raises you know and shows the importance of being able to challenge diagnosis and you know it's so easy for diagnosis to continue and it's really important that we have an open and honest conversation and that's why I think rheumatology MDT is so good that we're able to challenge each other and say well this isn't getting better and actually is the initial diagnosis correct.
 So yeah, so I think it was probably one of my consultant colleagues who shall remain nameless, who politely asked me whether it was worth re looking back at the biopsy, which, which is great, and I'm really grateful that that she did that
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   17:28
 Yeah, I think I think rheumatology MDTs are great because people, everybody has different thoughts and sometimes you won't necessarily think of something as someone will plant a seed in your head as well. What are the learning points you'd take away from this case?
Waters Lisa (R0A) Manchester University NHS FT   17:45
 Yeah. So I think this is kind of the very patient specific things pertinent to this case, so I think it's about the early review of patients, especially if there is diagnostic uncertainty. And I think, you know, we reviewed him relatively quickly and with that lack of Prednisone, it allowed us to just question the diagnosis. I think with Ian as well, you know he did have the kind of typical Sjogren's antibody. So he was A and a positive at an SSA positive and then he had the low C4, if you remember at presentation. And he also had a peripheral sensory neuropathy on his nerve conduction studies, which I don't think is typically explained by IBM having chatted to a few neurologists. So I think that's a learning point as well and when I've done a bit of reading about IBM, Sjögren disease can be associated with patients who have inclusion body myositis. So yeah, so that was a learning point for me and again, something about the typical kind of pattern recognition with these patients and the demographic. I think more generically you know this is. I mean, Ian is great and he's been really, you know, I think we've been able to be really open and honest with each other. And you know, the minute that we felt we'll be looking at the diagnosis, you know, we had the right rapport that I was able to say, look Ian, you know, this might be, you know, you've not responded, I might have got the original diagnosis incorrect and then there's something beautiful in the notes where he said, oh, I'm intrigued as much as you. And we've kind of been on this journey together and I think, you know, not all patients will be as understanding as Ian.
 And I think that's been important the kind of open and honesty approach and being transparent with patients as to where, where we're at as clinicians because these are complex cases and you know they're relatively rare.
 So yeah, I think that's they're probably my key points.
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   
 Yeah, yeah, absolutely. I think being open and honest, it's a really good learning point to being open and honest with patients because they are, they are complex cases. And I think, like you said, Ian was fantastic but I think sometimes if you are more open and honest with patients, then they’re more understanding and when you explain that actually this is this is going to be something very rare and they do tend to be more understanding.
Waters Lisa (R0A) Manchester University NHS FT   
 Yeah. And he's actually even said he wants to listen to this podcast. When I was doing the consent for him. So, yeah, I think, you know, he's been really gracious with it and, yeah we all learn from these cases, don't we? So I think as an MDT, we learnt as well. I don't think it was just me. So that's been a good part of it as well.
GALL, Stephanie (LIVERPOOL UNIVERSITY HOSPITALS NHS FOUNDATION TRUST)   20:20
 Absolutely. This has been a really fantastic case and thank you so much for your time.
Waters Lisa (R0A) Manchester University NHS FT   20:26
 Thank you. Thanks for having me.