Rica and IMPA

[Won]

Hi, thanks for adding me to the forum. I apologize in advance that this is probably going to end up being a rather long post.

Our Rica is a mixed rescue, 2yrs 10mths old now, and was 'diagnosed' with IMPA about 8 weeks ago. We live in Singapore, where veterinary information/access is limited, and apparently there is only one specialist that we were pretty much recommended not to visit. Rica was adopted at 2mths, we completed her puppy vaccinations but she's been vaccine free from then, and no further visits to the vet after being spayed at 13mths. She's always been sensitive and scared, and picky with food. In hindsight, I wish we had done more to help her deal with her stress, but easier to regret now I suppose.

Early March this year, she had an inflamed cheek, which appeared to be from a bee sting. She'd gotten stung before, and the swelling would go down pretty fast, but it did appear this one was moving from one cheek to the other and staying around a bit longer. I checked, best as I could to see if I could find the stinger, but couldn't find anything. Overall, she seemed fine and a week went by but then she started getting a little lethargic and she refused to go up and down the stairs. Her appetite was fine, and she was still moving around, so we thought she just needed to rest. A few days in, we started to notice she had a high fever, she was refusing to move much, and was very weak in her hind legs. When we took her to the vet, she was running a fever at 40.7 degrees, and the vet immediately put her on an iv of vit c and b, and amoxicillin. Her bloodtests showed high neutrophil levels but else from that, nothing was out of the normal range. After two days, her fever down at 38.5, we brought her back home with clavamox, and within a few days, we noticed her joints swelling up, complete loss of appetite and she started vomiting throughout the night. We took her back in and switched back to the iv administered amoxicillin. We started running all the tests to rule out tick borne diseases(lyme, babesia...), neospora, toxoplasma, distemper.... they all came back negative, in the meanwhile her neutrophil levels had spiked, and by her third blood test, all the other white blood cell related levels (monocyte, lymphocyte, eosinophil, basophil) had spiked as well. We had added enrofloxacin(baytril) on top of the amoxicillin by this point of time. Within a week, she had lost nearly 25% of her body mass(14.7kg -> 13kg), she wasn't eating anything and whatever she ate she was vomiting out. The vet then started mentioning that it was starting to look a lot like immune mediated polyarthritis, added unasyn to the baytril, did an ultrasound that came out clear, but it looked like we were going to lose her, so we went ahead and administered a dexason shot. Two days from then, we started her on the prednisolone. She was probably around 12-12.5kg at this point, and she was getting 5mg/q 12hrs, so at an anti-inflammatory dose. Within a week we had her down to 5mg/q 24hrs, and she was definitely starting to put on a bit of weight at this point. When we tried to take it down to 5mg/q 48hrs, we thought she was having a relapse. Her appetite was gone and she started to limp once again, and then we upped her dosage to 7.5mg/q 12hrs from which we have been trying to taper since.

It's been 8 weeks since we started her on the pred, and we have good days, but we are having a few bad days in the row right now. I've tried my best to read up as much as I could, but it was a bit late into our pred regimen when I came across this forum and started reading about how IMPA is treated elsewhere in the world. She's lost her appetite once again, and she'll spend a long time waking some of her muscles up. We live in a very hot humid climate, and with her panting, she's basically laying under aircon for the majority of the day. She is definitely showing signs of muscle atrophy, and we really are at the point, where we want to get her off the steroids. She's currently on 5mg in the morning, followed by 2.5mg in the evening.

We have her liver supported with milk thistle, and for the inflammation, she's getting some omega-3, turmeric powder, and she has an herbal blend of withania, devil's claw, and chamomile. We've read about some joint supplements that dogs with arthritis take, and will be adding on some more once they arrive in this country.

It could've been the bee(?) sting, but just knowing what her bloodtests had read on the first day, and how she responded to the clavamox, it does seem like it could have been an iatrogenic trigger of the IMPA. I have so many days when I wish I'd been more educated in caring for her and taken care of her fever better and sooner. I wonder if things would have been completely different. She'll be going in for a follow up blood test in about 10 days.

We never got the final conclusive diagnosis of this being IMPA. But somehow we've gone through the whole slew of antibiotics and 2 whole months of preds and it seems pointless to even go through the whole body anesthesia and joint tap now. We're just at the point where we want her immune system strengthened enough so she can have more happy/fun hours during the day.

Really happy to take any advice and input. And also my best wishes and strength to everyone dealing with their sick canine babies.

[Jo CIMDA]

Hi and welcome

I am sorry Rica has IMPA - well assumed IMPA.

It is not always possible to have a definitive diagnosis of AI disease but if the disease responds as it should to immunosuppressive doses of steroids then it is reasonable to assume a diagnosis.

Rica didn't have an immunosuppressive dose of prednisolone, but she probably had a boost with the shot of dex and she responded well.  Continuing treatment with an anti-inflammatory dose of steroid treatment probably tempered the IMPA,  until the dose was reduced and then the clinical signs started to return.  This is a familiar scenario when an AI disease like IMPA is treated with a lower than recommended dose of steroids.  An initial good response is seen but when the dose is rapidly reduced, a relapse occurs.  This is because the immune system was not sufficiently suppressed and also it was released too soon to achieve remission.

The most successful treatment of inflammatory AI disease is immunosuppressive doses of prednisolone given for a period of 10-28 days (the closer you get to 28 days the better).  Then the dose is reduced over a period of months until a low every other day dose is given and then hopefully, if remission is achieved, pred is stopped altogether.  If the dose is too low and/or the duration is not long enough, a relapse will occur -  and relapses of IMPA are not uncommon.  IMPA has a good prognosis and with correct treatment  long term remission is achievable and realistically  expected. 

If Rica is not back to good health and you are still seeing clinical signs of IMPA, then she needs to receive treatment that will significantly suppress her immune system and allow the autoantibodies that are attacking the synovial fluid within her joints to become non-existent so when you start to reduce the steroids the immune system will be back to normal function and remission is achieved.  Just tempering the symptoms is not a long term answer and remission will not be achieved.

As Rica has been on prednisolone for 8 weeks, and even at lower doses of pred than required, there will be a build up of corticosteroid in her body.  She is not a big dog so it is likely that she will have coped well with the side effects of the steroids, but only your vet can decide by a physical examination and perhaps looking at the level of her liver enzymes if she is able to cope with an increase of pred to an immunosuppressive dose (1mg/kg/12hours pred) in order to bring the disease under control and on the road to remission.  If Rica is struggling with the side effects of the preds then it is usual practice to introduce a 'combination' drug such as mycophenolate mofetil, leflunomide, or cyclosporine. A combination drug will provide the required immunosuppression buy other means, and it allows the preds to be lowered sooner. Mycophenolate has a quicker onset of action so this might be a better option.  Having said that I am not sure if you have these drugs in Singapore, but they are all human medicines, so they might be available.

https://www.mspca.org/angell_services/mycophenoloate-mofetil-the-latest-in-immunosuppressive-therapies-in-veterinary-medicine/

I know you want her off the steroids but if her IMPA is not under control she will not be back to her happy self and there is no choice but to address the autoimmune disease with the correct drugs and then look forward to weaning her off when it is under control.   

For a dog to develop an AI disease they have to have a genetic predisposition and then meet a trigger that causes the immune system to malfunction.  Triggers can be so many different things.  It is very possible that the trigger for Rica's IMPA was the bee sting. 
Jo



Reducing the Tablets
When significant improvement in the dog's condition is seen, usually between 10-28 days, the initial steroid dose is usually reduced by 25%. The dose is generally given for another 10 - 28 days and depending on the dog's progress and clinical signs the dose is significantly reduced once more for a further 10-28 days; and again in another 10-28 days. Anecdotal evidence has shown that if at this stage the dose is lowered more slowly, or reduced to an every other day dose over a period of months rather than weeks, relapse are less likely to occur.  It is always tempting to get your dog off steroids as soon as possible, but when treating autoimmune disease, as long as the dog is on a low, every other day dose then taking the last stage slowly seems to work best, depending, of course, on the severity of the disease and allowing for the difference in individual response - no two dogs reactions are exactly the same.  With some autoimmune diseases such as SLE, the dog is likely to be on steroids for the rest of his life. Usually an every other day dose can be achieved, but you risk a relapse if you take the dose too low. Below is the best example of a reducing immunosuppressive protocol I have come across. It is an excellent guide and can be adjusted to the individual.  Below is the bet protocol I have come across and it can be confidently used as a guide to immunosuppressive treatment.  Prof Day is among the top veterinary immunologists in the world. 


Example: Reduction Protocol for prednisolone:
Clinical Immunology of the Dog & Cat , 2nd Edition,  by Michael J Day
Professor Michael DayBSc, BVMS(Hons), PhD, DSc, DiplECVP, FASM, FRCPath, FRCVS 

Professor of Veterinary Pathology, University of Bristol, UK and WSAVA - Chairman of Scientific Advisory Committee.

This example is based on a dog receiving an induction dose of 1.0mg/kg/q 12hrs (q = every)
Dose                           Duration (based on clinical effect)
1.0mg/kg/q 12h                          10-28 days
0.75mg/kg/q 12h                       10-28 days
0.5mg/kg/q 12h                         10-28 days
0.25mg/kg/q 12h                        10-28 days
0.25mg/kg/q 24h                        10-28 days
0.25-0.5mg/kg EOD                    at least 21 days
0.25-0.5 mg/kg every third day      at least 21 days

Every reduction is made after consideration to improvement of clinical signs, blood results and side effects of the drugs.

Prednisolone:  "Doses above 2.2mg/kg/day do not give more immunosuppression but do cause more side effects. Many internists believe that prednisolone doses should not exceed 80mg per day, regardless of the dog's weight."  Plumb's Veterinary Drug Handbook Eight Edition.


How Do I Know if My Dog Will Relapse?
Until you have attempted to wean your dog off of the tablets for the first time you will not know if he is likely to relapse or not.  Sometimes during the weaning off process, before you even get down to an every other day dose, he may relapse.  If this happens then the drug dosage has to be raised, probably up to the last dose before the relapse (maybe a little higher, depending on the severity of the relapse) and then start the weaning process again.  If this happens again, then you and your vet may have to settle for keeping him on a low maintenance dose to achieve a good quality of life. A low, every other day maintenance dose of prednisolone is preferred to enable the dog's liver to rest in between doses. There are many autoimmune diseases that carry a good, drug free prognosis.  The more common, serious autoimmune diseases that may not need long term steroid therapy are: primary immune-mediated polyarthritis, autoimmune haemolytic anaemia and thrombocytopenia. However, as previously stated, all dogs are different and it very much depends on the individual dog, the severity of the disease, the experience of the vet and the vigilance and compliance of its owner.
If a relapse occurs whilst the dog is still being treated then true remission has not been achieved.  If the dog has achieved remission and has enjoyed a period without drugs or is on EOD maintenance drugs, when a relapse occurs or he develops another autoimmune disease, he has encountered a 'trigger factor' which has induced this change.

[Jo CIMDA]

P.S.

Rica should be on something to protect her stomach such as Ranitidine or omeprazole.

Jo

[Winstedt-School]

Wow ! so many information in one place, I love that forum !