Elsie/11 month whippet / relapse

[Erica]

Hi Jo, I am sorry to have to ask for advice but I find myself with differing opinions on steroid dosage. In brief, Elsie was diagnosed with SRMA on 29th September 2021. She had extensive tests and by cause of elimination she was diagnosed with SRMA. She had every test including joint taps but was getting increasingly poorly so I said no to the spinal tap. She was put straight on steroids at 2mg/kg. At that time she weighed 10kg. She didn't do very well on that dose. She had constant diarrhoea, was eating very little and lost a 1kg in weight. She remained on that dose for 9 days. At that point her CRP bloods were normal so the dosage was reduced to 1.5mg/kg/day. (I always split the dose am and pm). She was on 1.5mg/kg/day for 2 weeks then 1mg/kg/day for 2.5 weeks for 3 weeks. She was then on once a day 3mg in total for two weeks. At that point her CRP bloods were normal, she was well in herself, exercising normally, eating etc. Her dose was dropped to 2 mg per day. One week into this regime and I noticed her respiratory rate was increased and she was quiet. However she seemed to settled and the next morning seemed okay and cam for a walk. As the day progressed she started shaking, obviously in discomfort. I took her temp which was normal. I was worried though so took her to the vets who said her temp was a little elevated and they did a general and CRP blood tests. All came back normal. However, the vet was sure the (then mild) symptoms were indicative of a relapse so he said we should treat Elsie with 2mg/kg/day dose for two weeks. She currently weights 12.7kg so I gave her a 12.5mg dose that evening. By morning (today) she was back to normal. I repeated the 12.5mg dose.
We followed the protocol - the two/three week window was within the 10-28 days. She had normal blood tests at every stage.
I'd say she wasn't fully herself for about a month. She wasn't ill, just not ready to exercise etc. very much.
The vet said that the 1.5mg/kg/day is still an immune suppressing dose and not to worry that she only had the high dose for 9 days. She was very poorly.
My questions - why did she relapse? The 10-28 day window is a large one. Did she relapse because we went from 5mg down to 3mg too quickly? Should she have had a higher dose for longer? Is she a whippet that won't manage without steroids ? What protocol should I insist on now, after two weeks on the high dose, providing she tolerates it.
Many thanks for any help. Happy New Year. Erica

[Catherine]

It may be that the medication was reduced too quickly. I seem to remember some of her problems at the beginning could have been to do with the gastroprotectant?

Hopefully Jo will be along soon to help.

[Erica]

Thanks Catherine. I imagine that the doses were reduced to quickly but how does one know? The window 10-28 days is large and at each point her CRP was normal.

[Catherine]

I am a bit confused with the dosages. When she was started on 2mg/kg was that once a day or twice.....what was the total mg she had daily?

[Erica]

Hi Catherine - her protocol was -
29th September she weighed 10kg and had 10mg twice a day for 9 days

8th October she weighed 9.3kg, normal CRP, prescribed 7.5mg twice a day for 2 weeks
then 2 weeks 5mg twice a day
2.5 weeks 5mg once a day
2 weeks 3mg once a day
She was then reduced to 2mg per day and a week later showed symptoms previously shown at the onset
She now weighs 12.7kg
The vet took bloods - CRP normal - but symptoms suggested otherwise. This is odd to me as the vet relied on the CRP results to reduce her dose at every stage.
The vet spoke to a neurologist who said to give her 25mg for two weeks and reassess.
That evening I gave her 15mg (not wanting to give such a huge dose at once)
The following morning she was bouncing around and has stayed like that for the past 3 days. I am giving her 12.5mg twice a day.
Looking at the protocol which was following Day's in that the dose was reducing every 10-28 days, albeit on the shorter side. But why give a 10-28 day window if it should be longer?
From the research papers I have found on line, there seems to be no definitive treatment other than Day's and Tipold & Jaggy 1994, and Lowrie's study in 2010.
'Chatting' to people on line, it seems that vets aren't considering the immune suppressing dose seriously. One lady I spoke to has a whippet that has relapsed but the maximum dose has only ever been 8mg/day (and it's not a 4kg whippet!). Her vet's take on it was if the dog was stable on 8mg then that was fine. And if he needed to be on steroids for the rest of his life, well, that was fine too.
Another lady had her whippet on 2mg/kg/day for 4 weeks.
I thought that as long as you followed the protocol then the minimum time on steroids would be better. After all, they can mask other conditions.
Which part of the treatment is important? I understand that anything less than 1mg/kg/day isn't immune suppressing. The high dose sends the dog into remission so what is the point of the of the rest of the treatment i.e.the reducing doses? Is that just to wean the dog off steroids or does it play some part in the resolution?
The steroids don't actually fix the underlying problem, I think, they just hold the immune system at bay.
And in all this I could be totally wrong....

[Catherine]

Thank you for setting all that out, Erica. I must admit it can all be confusing at times especially when an owner is very worried about their dog.

As I understand it 1.0mg/kg twice a day is the minimum for an immunosuppressive dose. Unfortunately, some vets still do not understand autoimmune diseases and their correct treatment. The idea, as you know, is to suppress the immune system which is attacking itself. A certain amount of time has to be allowed for this, but then when the dog's system begins to right itself it still needs time to stabilize. All dogs are different and I also think the 10- 28 days is in case the dog starts to suffer with the medication and has to reduce sooner. I think generally, if the dog is coping on the medication, it may be best to aim for the longer time or something like 21 days each time and then towards the end of the reduction to take it very slow just for the system to adjust.

It can be so frustrating to have a dog relapse, nothing is certain from dog to dog. I am certain Jo can explain it better. She is aware of your posts and I am sure she will be along soon when she is able. I am afraid I do not know much about CRP.

How is Elsie? Has she been on a gastroprotectant?

[Erica]

Thanks Catherine. 
Elsie is fine. She seems very well. She is on a gastro protectant and I am collecting some sucrulfate for her as well today.

[Jo CIMDA]

Hi Erica

I must apologise for not joining in sooner. 

Every protocol has to be tailored to the individual and it is a guide only. I wish it was a simple as following a reducing protocol but unfortunately it isn't because every dog has the potential of coping differently, and whippets are a classic example of this individuality.

From what you have written I would think that Elsie did not reach remission, and her immune system was only tempered, possibly because the duration of each stage in the protocol was not long enough, and therefore as the drugs were lowered it allowed any remaining antibodies to reactivate and start to attack again.  The fact that she picked up so quickly when the steroids were raised again supports this. 

One cannot go by CRP levels alone, as prednisolone will reduce these, and there is no way of knowing if a dog has reached true remission until after the preds have been withdrawn for a few weeks.   If the dog relapses during the reduction programme then it is most likely that the dose was not given for long enough, or it was not a high enough dose,  and as the dose was reduced and the immune system released,  there were still active aberrant immune cells present.    Clinical signs and response to treatment are the most reliable indicators.  Relapses are not unusual, but this doesn't mean that she won't reach long term remission, nor that she will be on steroids for the rest of her life.  This is just a blip.

The 10-28 days window is broad because it depends on which AI disease you are treating, and it also depends on how the dog copes with the side effects.  It has to be tailored to the individual.  Anecdotally, I always think if you can get to 2 weeks, and the dog is still coping well, then go to 16 days, and then if she is still coping then 18 days and then 21+.  21 days is a good time to be on a single dose of preds before reducing the dose.  Checking every day if all is ok, and if it is, then you get on with your day, and do the same the following day. So if you can go to 21 days before reducing the dose,  then I think that gives better results long term. It is 'suck it and see' unfortunately!

If a dog is not coping with the side effects of the preds, perhaps because they have had a relapse, and they have had to go back onto a higher pred dose, then it might be worth considering adding a 'combination' drug eg., a different immunosuppressive drug that will contribute to suppressing the immune system but will not have the same side effects as the preds.  This combination method of treating AI disease usually means that the pred dose can be reduced sooner than would have been, had a combination drug not been used, and this is very helpful if the dog has unacceptable side effects. 

The 'combination' drug that I currently favour, and has had some remarkable results, is Mycophenolate Mofetil (MMF).  This might be an option for Elsie in the future, but for the time being, because she seems to be doing well on the higher dose of preds, I would say that it isn't necessary to introduce another immunosuppressant drug, but it is certainly something to consider should she need to go back onto higher doses of preds in the future. 

The aim is to totally suppress the immune system with drugs, and when it is released it is hoped that there will be no immune cells left that are targeting the dog's own body.   If this has been achieved, then as you release the immune system (by reducing the drugs) the immune system will be back to normal function again.  If, for a while anyway, the dog shows no signs of being unwell then it is hoped, or assumed,  that long term remission is achieved, but if symptoms start to appear again, then dog will have encountered a 'trigger' for the immune mediated diseases to return.

I hope this makes things clearer for you.  Fingers crossed that this time Elsie will achieve long term remission.

I apologise once again for my late reply.

Jo

[Erica]

Hi Jo,
Please don't apologise. I appreciate the time you have taken to write your reply. I understand better now. She seems remarkably well at the moment on the 2mg/kg/day. I will see if we can push this to 21 days. I might have to fight our corner with the vets.
I have some sucralfate tablets for her now as well. I think I read somewhere that they should be dissolved before administration and on an empty stomach?
Thanks again
Erica

[Jo CIMDA]

It is good to know that Elsie is doing well. 

Second time around, you want this to work, so if it can be pushed to 21 days then that would be best, but as always any adverse effects have to be taken into consideration and the dose adjusted if need be.

Sucralfate should be given on an empty stomach if possible,  but not within 2 hours of other drugs (as it can inhibit absorption of drugs)
It should be given several times a day to be most effective.   
If liquid, then shake before given. 
It is best to crush tablets and dissolve them in warm water just before administration.
REf:  Plumb's Veterinary Drug Handbook, 8th Edition. 

Fingers crossed that this time Elsie will reach remission.  No reason not to!

Jo

[Erica]

Thank you x
Do the steroids have any lasting, detrimental effects on young dogs? Elsie isn't yet a year old.

[Jo CIMDA]

Hi Erica

A possible effect can be calcium absorption that can lead to osteoarthritis later on.  I have not heard of a dog having calcium supplements to counteract this effect.  Also, just because this can be a side effect it doesn't mean that it will be.   It is all about the risk/benefit assessment and when treating a girl like Elsie, prednsiolone is the main stay of treatment.    I can't remember if I have ever mentioned adding a 'combination' therapy drug, but certainly if Elsie has to go back onto immunosuppressive treatment again then a combination therapy would be worth consideration.

I hope she is continuing to do well.

Jo

[Erica]

Thanks for the reply.
Elsie is now on day 10 and doing okay. I am very anxious about it though.

[Erica]

Short update. We are on day 17 of the 2mg/kg/day. All is well. Whew.
Quick question- should the dose be adjusted if Elsie gains weight? Ta

[Jo CIMDA]

Day 17 - well done!

No, don't worry about Elsie gaining weight.    If she starts to get a big pot belly, and huffs and puffs a lot, then it is time to reduce, but to a certain extent gaining weight is to be expected. One of the temporary side effects of preds is fat deposits.

Jo