Saba - 10 year old vizsla with IMPA

[Becca]

Hi there - we're new to the forum but feel a lot better informed having read through many of the posts in the last couple of weeks. Saba, a hungarian vizsla, was diagnosed with IMPA a couple of weeks ago after 2-3 weeks of deterioration. It seems that the problem started 6-7 weeks ago with what we think was a knock to her front leg which left her totally lame. She was x-rayed and it was confirmed that she has a reasonable degree of osteoarthritis. NSAIDs were prescribed. The initial limp improved slowly but in about the fourth week she started to go downhill. She was then given more NSAIDs and tramadol. After a week of that she could hardly stand and shook and whimpered throughout the day and night. We took her off tramadol thinking she was having a reaction to that but that didn't really have any great impact. Then the limp appeared in her back leg. X-rays confirmed no bone cancer evident there and bloods looked fine. The next day however, her joints were incredibly swollen and hot. That led to the eventual diagnosis. She then had a scan to confirm if there was a primary cause such as a tumour but fortunately nothing evident.

She was placed on 25mg of pred twice a day. She did weigh close to 28kg at the beginning of this but as of today, 2 weeks into the pred, she is down to just under 24kg. The swelling resolved very quickly and she definitely has become more mobile and generally happier. However she has started vomiting intermittently, has lost a huge amount of muscle mass and now has clicking bones just 13 days into treatment. We took bloods today to check liver function etc. ALT and ALKP are up from 38 U/L to 627 U/L and 87 U/L to 1976 U/L but our vet feels this is consistent with steroid use and is not overly concerned. However he has recommended reducing the pred to 20mg twice a day as of now. I'm torn - I hate what the drugs are doing to her but I'm a little concerned that this is possibly a bit earlier than ideal to start the tapering when looking at the Michael Day protocol. The other vet we went to had recommended staying on the 25mg twice a day for two months which seemed extreme on the other end.

I'm interested in knowing what increase in risk of relapse do we face by reducing at 14 days rather than say 21 days or even the 28 days. ie is 14 days reasonable?

I guess my other comment / query is whether anyone has seen a connection with NSAID use and immune mediated disease onset? I can't help but draw a link between Saba being on Onsior (Australian brand name, not sure of UK equivalent) for a month and IMPA starting. My suspicions are raised by the fact that we had another vizsla who reacted very badly to Onsior some years ago. I put that down to her having various health issues. However we also looked after a 12.5 year old vizsla earlier this year who had been on Previcox for about 6 weeks as well as thyroxin. While she was staying with us she was diagnosed with IMHA and we very nearly lost her with her PCV down to 13. Fortunately she is still with us and is so far successfully but slowly tapering off her medication. So three dogs (all vizslas), three cases of NSAID usage for 4 weeks plus continuously and 2 immune mediated diseases and one other potential liver etc issue problem. Coincidence?

[Jo CIMDA]

Hi and welcome

I'm sorry Saba has IMPA. 

She responded well to steroids and this is a very good sign, and it all but confirms a diagnosis of IMPA.  The high  liver values are to be expected and usually it does not become a problem if the steroids are reduced correctly. 

If you reduce the steroids too soon you do risk a relapse, so the alternative could be to introduce another drug, such as Azathioprine, which will support the immunosuppressive treatment and perhaps allow the steroids to be lowered more quickly and still maintain a significant level of immunosuppression. Azathioprine doesn't reach its full potential for 6+ weeks, so it is best to introduce it at the early stages of treatment.  There are other 'combination' drugs that can be used. 

Also, perhaps you could ask your vet for a gastroprotectant, such as Ranitidine or Omeprazole, and that might help with the vomiting.  Keep Saba on a low fat diet too. Preds can induce pancreatitis and you should avoid that if you can. Saba's joints might be a bit dry so limit her exercise until the synovial fluid within the joints has the time to regenerate. 

The Michael J Day protocol is a great guide to immunosuppressive treatment and certainly 2 months is too long for a dog, especially a large dog, to be on the initial dose immunosuppressive dose of steroids without unacceptable side effects.  The side effects of the drug can become a problem if the duration is prolonged more than necessary. If the dog has to be kept on high doses of preds for much longer than expected then a 'combination' drug (as mentioned above) should be introduced.

Whether Saba will relapse after only 2 weeks on the initial dose remains to be seen, all dogs are different, but a relapse is more likely after only 2 weeks of immunosuppressive treatment.  If she does relapse you will have to raise the preds up to 1mg/kg/12 hrs for another few weeks and this means she will ultimately be on the higher doses for longer than if you kept her at the initial dose for another week or so now. If your vet is not overly concerned, then why does he think the steroids should be reduced at this time?   If Saba is coping with this dose then perhaps you can eek it out to another week before reducing, but only you and your vet can assess this.

No one wants their dog to have steroids but when it comes to autoimmune disease steroids are a life saver.  You can see how quickly Saba responded to the drugs and the reason is because they suppressed the immune system and stopped the immune destruction of the synovial fluid within the joints. The idea now is to reach a stage when her immune system returns to normal function, and then you can slowly release it by reducing the steroids and ultimately achieve remission.  It can be done!  No one knows the exact time to reduce the steroids but the M J Day protocol is the best guide, but still it has to be tailored to the individual dog.

Some drugs can be a trigger for AI disease but so can the medical conditions for prescribing those drugs too.  Anything within the dog's environment that challenges the immune system can trigger an AI disease in a genetically predisposed dog. Some drugs are known to be worse than other drugs, and some dogs will react badly and others won't.  My own personal experience of Previcox is not good and I will never be sure if it was Previcox that caused one of my dog's to develop kidney failure.  I truly sympathise and understand how difficult it is to make the decision to use conventional medicines, and at the same time have serious reservations about their use.

I hope you can feel more confident about whatever you decide.

Jo

[Becca]

Thanks Jo. This forum is wonderful for its information and its moral support.

Saba is on a gastroprotectant - thanks to this forum. The vet who recommended the 2 months of pred at high dose claimed it wasn't necessary but I went back to my regular vet and he agreed it was a sensible precaution. She is also now on anti nausea medication.  She's on a raw diet and I keep it low fat since she had an episode of pancreatitis a couple of years ago. So hopefully we are keeping her as "well" as we can. The weight loss is scary but we can work on that a little further down the track.

You confirmed my fear that she would be better off continuing at the high dose for at least another week. It's difficult to do this when you see them so out of sorts - she was very pacy last night and couldn't settle, plus the vomiting, plus the huge change to her body shape etc etc. However it may be worth battling on a little longer if that avoids having to end up back at square one. I had already cut her down to 20mg this morning but I'm thinking I'll do a ditherer's compromise and give her 25mg at night for another weak. Given she is down to about 23.5kg, that pretty much is still at the immunosuppressant dose.

I'll speak to our vet about introducing a combination drug. I'm not entirely sure what the theory is here - is Azathioprine not a steroid but acts in a similar but gentler way?

Thanks again for the time you put into responding to everyone.

Rebecca

[Jo CIMDA]

Hi Rebecca

One has to look at the whole picture to be able to decide when to lower the steroids and by how much.  Every dog is different and the clinical signs can only be assessed by looking at the dog and assessing the present clinical signs along with the blood results. Sometimes it is as important to lower the preds, because of intolerable side effects, as it is to control the disease. One mustn't override the other and an acceptable balance should be achieved.

I am so glad Saba is on a gastroprotectant, and her diet sounds great.

Have you any inclination why she was so pacy last night.  Do you think she is in pain or is it the side effects of the steroids, or is something else becoming a problem - like pancreatitis? Is her behaviour similar to when she had pancreatitis before?

Check that her red blood cells and platelets are not going too high.

'Combination' drugs, such as Azathioprine, Cyclosporin, Leflunomide etc.....  are immunosuppressant's and they are commonly used in the treatment of AI disease.  They are not necessarily 'gentler' (all drugs can have their downside)  but they act differently to prednisolone therefore the side effects you see with the prednisolone can be reduced because a combination drug can allow the vet to reduce the steroids. Cyclosporin and Leflunomide etc., (there are others)  can be used as a primary drug if the steroids need to be reduced quicker than usual but their onset of action isn't as quick as prednisolone.

Assess the way she is every day and if you feel her medication needs to be changed then have a chat with your vet.

I hope she is feeling better very soon.

Jo

[Becca]

Thanks Jo.  Our vet doesn't think the vomiting and paciness is pancreatitis due to the blood results, the fact she still has a good appetite and that she has no diarrhoea. He was a little surprised that it would be the pred that was making her nauseous but I guess every dog reacts differently. 

The anti nausea seems to be working well for the moment - she seems a bit brighter since yesterday morning and at this stage I think I'll keep on with the 1.25 pred at night and the 1.0 in the morning for another week before deciding to drop down any further.

Rebecca

[Becca]

So things seem to have gone horribly wrong. Saba has pretty much struggled with pred since about a week after we first started her on it (Nov 17th). A blood test after a couple of weeks was probably as expected but she was vomiting nightly on the 50mg and 45mg per day dose. She weighs about 23kg currently having started at 27.5kg. We reduced to 40mg after 20 days on these higher doses and introduced Imuran (azathioprine) on Dec 11th. We got through 8 days of the pred on 40mg and then reduced to 35mg or about 75% of her bodyweight across the day. That lasted about  12 days before she had very bad bloody diarrhoea and was very weak so we reduced to 25mg on 27th December. Imuran was initially 37.5mg daily for 11 days and then reduced to 25 mg every second day.

She has been very lethargic throughout but this went to a whole new level a few days ago. She is weak all over and finds it difficult to stand up. She is still eating. We ran blood tests today and it doesn't look good. ALT and ALKP are off the scale and AMYL and LIPA have more than tripled from the high levels in the first blood test. She's anaemic and white blood cells are normal - apparently they should be high given she is on pred. Our vet seems to think/hope this is a drug induced pancreatitis and has told us to remove the aza as perhaps that is the culprit. I can't see anything in the side effects of aza to suggest this is likely to be the case and just feel worried sick that we are losing our girl.

I keep wondering if there is a primary cause of all of this we haven't discovered but she was x-rayed and scanned at the beginning and this didn't suggest any tumours etc. plus her blood work was at that stage perfect. She responded brilliantly for a day or two to the pred but it has been a struggle ever since.

I don't want to give up on her but I don't want to her suffer and it seems that the cure is hurting her as badly as the initial IMPA. Is there any reason for us to have any hope at this stage?

[polly]

Don't give up  hope. Ask your vet for a referral to a specialist or a University vet school clinic.  If you are in Uk (like most on this site) probably Jo can help suggest  the best place to go in your area. I can't offer that kind of advice as I am in Australia, but I understand how desperate you must be feeling when you can see  your dog suffering.

[Becca]

I'm in Melbourne. I guess Werribee is an option but at the moment all we can do is hope it's the aza and it's reversible. I guess my question is whether it's more likely to be the pred and should that be the one we're reducing.
I have this afternoon found reference to one paper where the indication was that aza caused acute pancreatitis in a couple of dogs. They came right when it was removed. Pinning my fading hopes on Saba being the third.

[Catherine]

....." she was vomiting nightly on the 50mg and 45mg per day dose. ".......

Do you mean she was having 50mg daily then you reduced to 45mg daily or do you mean she was having 50mg in the morning and 45mg in the evening? (95mg DAILY would be much too much).

Perhaps you are reducing too quickly?

Is Saba having a gastroprotectant? If not that could be causing the sickness, stomach problems etc.

The liver levels often increase a lot but when the steroids are reduced they will start to go back to normal.

[Jo CIMDA]

Hi Rebecca

I'm sorry to read about this news. I am not clear about the drug protocol Saba has been on, so if I get it wrong then please excuse me.  I would check the Michael J Day protocol (see below) and compare it to the protocol that Saba has been on.  It is a great guide to treatment.

Clearly if her liver enzymes are very high then the preds need to be lowered.  This is most likely to be the cause of the clinical signs you are seeing.  The Azathioprine can cause bone marrow depression but clinically, this is rarely too much of a problem.  In addition, when a dog has been on high doses of preds for a long time this can also cause bone marrow depression and often the red cells won't start to increase until the preds are lowered. Preds can also cause pancreatitis and as the AMYL and Lipase are raised I would imagine the preds are causing these problems.  It is well documented that preds can cause pancreatitis.  I can understand why your vet wants to lower the Aza but it is more likely to be the preds that are doing more harm than good and are the root of Saba's current problems. This is all very typical of uncontrolled steroid induced Cushing's disease and this can be life threatening.

By now Saba should have been weaned down to a very low dose of preds.  It is very unlikely that after being on high doses of preds and Imuran for so long that her IMPA isn't in remission.  Personally, I don't think you have any option but to lower the preds and quite significantly too.  There comes a time when regardless of the autoimmune disease the drugs have to be lowered because they will do more harm than the disease.  If Saba's IMPA relapses then so be it, another drug such as Leflunomide can be used to bring it back under control but right now your biggest problem is the preds and this should be addressed immediately and it can be serious but at this stage you have a chance of retrieving the situation for Saba. Below is an extract from my seminar notes and I hope will give you some information you can take to your vet.  PLEASE, seriously consider that it is more than likely to be the preds that is causing Saba to be so poorly and something has to be done today. 
Good luck
Jo


WHAT TO EXPECT ONCE TREATMENT HAS STARTED
If a dog has a serious autoimmune disease, then the sooner treatment commences the better chance the dog has of survival.  The main delay to starting treatment is obtaining a diagnosis or at least your vet being sure that he hasn't missed anything that could be made worse by giving high doses of steroids.  Achieving a diagnosis can be a fight against time. 
If your vet has decided that in all probabilities your dog has an autoimmune disease, then to a certain extent, which autoimmune disease your dog has, as far as treatment is concerned, is irrelevant because with the exception of a few diseases, they are all treated the same, that is, with immunosuppressive drugs.  The main objective is to 'knock out' the immune system and virtually stop it from working (or near enough) so the destruction will cease and give the body a chance to recover.  As previously stated, this treatment regime works in most cases, that is, if it has been given early enough and the dosage is correct.  All dogs are different and some can tolerate the drugs better than others. In proportion to their size, small dogs seem more able to tolerate higher doses of steroids than large ones. Some diseases are more serious than others and carry a poorer prognosis. So the initial crisis is a crucial time, however anecdotal evidence shows that many more dogs survive than die if correct treatment is administered in good time.
It is hoped that a positive response can be seen within 4-6 hours of starting treatment (depending on the disease), but in a serious, life threatening situation, the first 2-7-14 days can be a very worrying time.  Assuming the dog has stabilised he will quickly feel much better, and if he is in hospital may be allowed home within a week.
When he comes home he will probably have a 'goody bag' full of drugs.  He will be on a high dose of steroid, usually prednisolone, and he may also be on another immunosuppressive drug, such as Azathioprine.  Your dog will be weaned off in a controlled manner according to his wellness and clinical observations. 
Note: High doses of steroids must not be stopped abruptly.  Your dog could go into an adrenal crisis if the medication is withdrawn too quickly. 
In addition to immunosuppressive drugs he should have something to protect his stomach from excess acid.  The last thing your dog needs when he is feeling poorly is a bleeding stomach ulcer caused by the drugs.  Sometimes, Antepsin is given to coat and protect the stomach (but this must not be given within two hours of other medication otherwise it will stop the drugs from being absorbed).  Zantac (Ranitidine) may also be prescribed to take away the excess acid. Another gastroprotectant used is Omeprazole. To minimise irritation to the stomach it is usual for the daily dose of steroid to be split into two doses and given with food, one dose in the morning with breakfast and the other dose with his evening meal. I have known several dogs, who did not receive a gastroprotectant as a part of their treatment regime, and went on to develop anaemia. This is not autoimmune haemolytic anaemia but iron deficiency anaemia caused by bleeding stomach ulcers. Using a gastroprotectant is a good preventative measure. When the steroids have been significantly reduced to a low dose, a gastroprotectant may not be necessary.
Excess acid, produced because of the drugs, may make a dog prone to developing pancreatitis. A dog with pancreatitis will appear in pain and his back may be arched as if he can't straighten up.  He may be lethargic, seem bloated and have a tender abdomen. Dogs usually go off food and water, may vomit and look depressed.  If you suspect that your dog has pancreatitis, don't try to feed him because it will make the condition worse. Take him to the vet as soon as possible as he may require treatment or need to go on an intravenous drip to stop him dehydrating.  Again, the risk of pancreatitis should be minimal once the dog is on a lower dose of steroids.   A low fat diet is best when your dog is on high dose steroids or prone to pancreatitis. 
As your dog's immune system is being significantly suppressed, he will be more likely to pick up infections, and will not have the ability to fight against them.  As a precaution a broad spectrum antibiotic is often prescribed. Also it is sensible not to exercise him in areas where he is more likely to encounter infections, for example, a park or a popular dog walking area. 
Whilst your dog is on high dose steroids he will want to eat and drink excessively. However, this also means that he will want to urinate more and this can sometimes cause temporary incontinence.  You may have to get up to let him out during the night and if you leave the garden door open during the day, it may save some mopping up!  He cannot help it and won't like it either, so don't be too hard on him, it's only temporary. You will notice as he is weaned off the drugs the unwanted side effects will subside and he should return to normal habits and behaviour.  Urinary tract infections and/or bacterial skin pustules are not uncommon when a dog's immune system is suppressed, and this is often the reason for a dog to be off colour during this time.  Note: Always consider a urine infection if your dog seems under par.  A course of antibiotics will usually sort this out quickly.
Depending on what autoimmune disease your dog has, he will probably need to have regular blood tests.  Biochemical blood tests will also keep an eye on other body functions, such as those of the liver and kidneys, which is important at this stage.
Assuming good progress is being made, the clinical signs of his illness are diminishing and positive signs of improvement are apparent, your vet will want to start weaning him down from the high doses of steroid.  This process can take 3-6 months or more, and usually begins anytime after 10 - 28 days from the start of treatment, depending on the results of his blood tests and his clinical signs.
Relapses are not uncommon, especially in diseases that are difficult to control, for example SLE.  A relapse may mean that initially, your dog needed to be on a higher dose of immunosuppressive drugs for a longer period of time, or your dog may have been weaned off a little too quickly and then the dose withdrawn too soon.
If a relapse occurs he will probably show similar clinical signs to his initial crisis.  He will have to go back on an immunosuppressive dose of prednisolone, but it may not have to be quite as high as before. A combination drug may need to be added at this stage. The weaning process will then have to start all over again. Returning to an immunosuppressive dose will mean that he has to go back on a gastroprotectant.
Side Effects of the Drugs – Iatrogenic Cushing's Syndrome
Iatrogenic Cushing's syndrome is a side effect of high dose steroids and is caused by too much corticosteroid in the body. To a lesser extent, the immediate side effects observed when the dog initially goes on steroids eg., drinking, eating and urinating excessively is a mild example of Cushing's syndrome.  Personally I like to see dogs responding to high doses of prednisolone in this way, as it means that they are responding to the drugs as they should.
Usually, Cushing's syndrome only becomes a real problem when exceptionally high doses, or prolonged high doses of steroids are administered, maybe due to a relapse, or in some cases where the vet is inexperienced in reducing steroid doses and keeps the dog on a high dose for longer than necessary; or when the dog is not responding to treatment and higher doses are necessary to control the disease.  This is where the cytotoxic drug Azathioprine is very useful. 
All drugs carry side effects and Azathioprine is no exception, but it does not carry the same side effects as prednisolone, therefore by using this drug in combination with prednisolone it reduces the risk of iatrogenic Cushing's syndrome.  As Azathioprine takes at least 10 days to take effect, starting the 'combination' therapy at the beginning of treatment may enable the prednisolone to be lowered within the 10-28 day band and still maintain a good level of immunosuppression. If your dog is not responding to treatment then your vet may consider changing his treatment to other immunosuppressive drugs.
How Can I Tell if My Dog Develops Iatrogenic Cushing's Syndrome?
Iatrogenic means 'drug induced'.  Clinical signs of Iatrogenic Cushing's syndrome are the same as primary Cushing's syndrome but can present with acute clinical signs. It reflects the level of corticosteroid in the body.
The most notable side effects are, heavy panting, some hair loss, and an increase in drinking and urinating, excessive pigmentation.  This is something everyone seems to be aware of and accepts as normal when a dog is on high dose steroids. Very often the dog will be weaned down to a low dose before any major problems arise.  Acute Cushing's syndrome due to overdosing of corticoid steroids can be very serious.  Blood results will reflect this, especially the liver enzymes which may be extremely high. Blood platelets may also be high and blood clotting may be a risk.
So when should you alert your vet to suspected, unacceptable level of corticosteroid?  The owner should take note when other clinical signs occur, such as: Depression, anorexia, muscle wasting and extreme weakness, lethargy - unwillingness to exercise, skin lesions and thinning of the skin, excessive hair loss, pot-bellied appearance and sagging back, behavioural changes (aggression).
If your dog is showing these signs it will probably mean that the dose of steroids needs to be lowered. It is important that it is not confused with a relapse of the dog's condition or an infection. The dilemma is that steroids must not be withdrawn too quickly otherwise the dog may go into an adrenal insufficiency crisis.  If the clinical signs of iatrogenic Cushing's syndrome is intolerable, it is hoped that the high dose of steroids that he has been on will have already done their job and that his autoimmune disease will be stable. As long as the steroids are lowered in a controlled manner and in time, all the symptoms of Cushing's will subside and your dog will return to normal, but extreme signs must not be ignored.
The Importance of Correct Treatment and Dosage
Iatrogenic Cushing's syndrome may also occur if the vet has initially prescribed a dose too high for the size of dog being treated.  For example:  I received an email from the owner of an Irish Setter, with AIHA.  The dog was prescribed 200mg of prednisolone each day. I called the owner, only to hear that the dog had to be put to sleep that day.  I was not surprised. The poor dog was on nearly twice the highest, recommended dose of prednisolone.  She was 9 years old and had never had a day's illness in her life.  What a terrible shock for the owners and what a lot of unnecessary suffering.  I know what it feels like because I too, have lost a dog due to prescribed overdosing of prednisolone.  The feelings of responsibility are enormous.
In contrast, some dogs are not treated with enough prednisolone.  Here's another story:
A greyhound diagnosed with immune mediated thrombocytopenia (IMTP).  Her vet gave her an initial shot of dexamethasone (a steroid which is 6 times stronger in terms of glucocorticoid activity than prednisolone).  Some vets choose to give a shot of 'Dex' as an initial therapy in autoimmune disease, especially if the patient is acutely ill.  Its effects can sometimes be seen within 6 hours and lasts for 36-72 hours.
The vet did really well and a marked improvement in her clinical signs was seen. It is usual, 24 to 48 hours after the shot of Dexamethasone for the treatment to change to an immunosuppressive dose of prednisolone tablets and for the owner to continue treatment in the usual way.  However, the vet only prescribed 5mg of prednisolone a day. The owner said they were very concerned that after a few days of improvement, she seemed to be very poorly again.  The vet couldn't understand why she was not continuing to improve.  He gave her another shot of Dexamethasone and the same improvement was seen.  I suggested to the owner that she either spoke to her vet about putting her dog on an immunosuppressive dose of prednisolone or change her vet.  They saw another vet in the practice, who was more experienced in treating autoimmune disease, and the dog was put on the correct, immunosuppressive dose of prednisolone and the treatment was successful.
These case histories demonstrate how important it is to treat promptly and correctly.
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 up to half. 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.


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.
The dose of azathioprine 2mg/kg/24 or 48 hrs, can be reduced initially by giving a lower dose tablet per day, or gradually reducing from daily dosing to every 2nd day, every 3rd day, every 4th day etc.....  Remember, azathioprine tablets should not be broken or handled without gloves.
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.

[Becca]

Thanks Jo
Just to clarify Saba's pred protocol to date:

25mg every 12 hours (50mg daily) for 13 days 
20mg & 25mg (45mg daily) for 7 days
20mg & 20mg (40mg daily) for 8 days
15mg & 20 mg (35 mg daily) for 12 days
10mg & 15mg (25 mg daily) for 17 days

The small steps down were made due to adverse clinical signs and trying to balance that with the danger of relapse.

Imuran was 37.5 mg daily for 11 days and then 25 mg every second day which she has been on for 2 weeks.

My gut feel is that is the pred rather than the aza. She responded really well for the first few days but then it has been a slow ratcheting effect down in terms of her general wellness. The other dog I know of on the same drug regime had considerably more energy so the comparison has worried me but I've been told it's normal to expect lethargy and depression.

You mention lowering the pred significantly. My thought was to bring it back to 10mg daily spread across the day. Are you suggesting a more drastic reduction or do I start there for a week and then lower further? Sorry - I know you're not a vet and I will seek referral to a further specialist tomorrow but I'm keen to have your input as to what is sensible.

My initial dilemma is what to do in the morning before the vet opens and I can have a further discussion. My current thinking is that I will reduce the pred to 5mg.

I guess the other question is whether we should actually be continuing with the aza but hopefully a specialist can help in answering that.

Again my thanks for all your support.

Rebecca

[Jo CIMDA]

Hi Rebecca

Individuals respond differently to drugs -  especially hormones, and this is why an immunosuppressive drug protocol has to be tailored to the individual but along certain guidelines.

Although often lowering the preds slowly can produce better results it is usually done after they have been significantly reduced, say after the third or fourth reduction,  and then it can be taken slowly when the dose is at a more tolerable level.

Prof Day's protocol (and this is only a guide) recommends reducing by 25%.  In comparison, Saba's protocol has only been reduced by 5mg at a time which is considerably less. So Saba has been on a high level of steroids for a long time and this is most likely to be the cause of her present clinical signs and blood results.  Like you say I cannot direct you but I can give you some information that you can discuss with your vet. Lethargy and depression is to be expected but to what degree?  Not to the extent of the dog's life being threatened.

When a dog has been on prednisolone for a long time their adrenal glands shut down production of the glucocorticoid hormone (because it is being artificially produced by the prednisolone).  The part of the adrenal gland that produces glucocorticoid has to 'wake-up' and start producing again, and this is another reason why the dose is gradually lowered.  You cannot stop the preds suddenly because this is cause her adrenal glands to go into crisis, so the minimum you must give is 0.2-0.4mg/kg/per day (which is the replacement dose for dogs with Addison's disease, and who are unable to produce it's own glucocorticoid hormone). 

If you take Saba's original body weight of 27kg then the minimum dose you can reduce it to is 5.4mg - 10.8mg prednisolone per day and then gradually wean it off over a period a couple of weeks.

Your vet will have to examine Saba and assess how urgent it is to lower the dose, taking into consideration her blood results.  If for example a dog needed life saving surgery whilst on preds then the lowest dose  the vet could reduce it to would be 0.2mg/kg/a day.  This would be essential for the survival of the dog. Saba needs it to be reduced because she is saturated with the effects of preds and how much reduction can only be determined by assessing the whole situation.  What you don't want to do is to lower them too quickly if it is not necessary because you want to try and maintain remission. 

My gut feeling, if Saba really need the preds to be significantly lowered to address the current situation, would be not to lower it less than 10mg a day.  This dose is virtually just supporting the adrenal glands and when you gradually reduce the preds further the adrenal glands will start to function and start to produce on their own.

In the past a dose reduction protocol for immunosuppressive doses of preds would have been by 50% each time.  In later years the 25% reduction has been adopted because it tends to produce better long term results.  So, only a vet looking at Saba can decide, but the dose can be reasonably reduced by 50% or if necessary the dose can be 10mg pred given once a day in the morning. This way you are going to make her feel a lot better because it is the drugs that is causing this problem, and you are significantly reducing the dose, and also her adrenal hormones are being supported whilst her own adrenal glands start to function again.

What have you got to lose?  Your vet may not have the necessary experience to recognise when a dog is saturated with prednisolone, many don't, but you can have a good and positive discussion now, I hope. Good luck tomorrow.

Jo

[polly]

I'm in Melbourne too.  I hope that Jo's suggestions are helpful.  Print  them out and give them to your vet so he/she  can  discuss  the problems with  a more experienced colleague and/refer you to  specialist. . Not a good time of the year  to get help when so many vets will be on holiday.  My dog  had IMHA - he's OK now.
Good luck.

[Becca]

Thanks Polly and Jo.
We have met with our vet again and I understand a little more as to why he thinks it is the Imuran that should be removed. He is not overly concerned with the pancreatitis given she is still eating and not vomiting. The more significant problem at the moment is the liver and the fact that ALT and ALKP are off the scale and he believes that she might be one of those rare cases where Imuran can cause acute hepatotoxicity. He agrees we can't know for sure.

I have reduced Saba's pred to 5mg this morning with the intention of giving another 5mg this evening. I had then intended going to 10mg in the morning only as of tomorrow but as she is now booked in to see a specialist at 10am and they have instructed no food, I'm probably going to hold off giving her any in the morning until after the appointment. My vet is still reluctant about this drop to 10mg, warning me that we could see a relapse. As you said Jo, if that's the case so be it. I think the risk to her life of her remaining on 25mg is equally as high if not higher. Hopefully 57 days at higher doses have been enough to put her and keep her in remission.

The specialist is a bit of a compromise - I'm not entirely sure that they are well versed in auto immune diseases but we couldn't get in to the one I wanted to until next Wednesday. I don't think we have that time on our side. At this stage I'm just keen to hear a second opinion on my vet's theory of it being the Imuran.

So in summary we have discontinued the Imuran and reduced pred to 10mg per day. I don't know that it will be enough to save her but it's all we can do at this stage. She's very weak but at least she is still eating and drinking.

Again, thank you for all your helpful input. It makes a horrible journey just that little bit more bearable.

[polly]

Thanks for the update. I hope tomorrow's visit to  the specialist will help show the way forward. When my dog was initially on very high pred his muscles wasted  to such an extent that he could  barely stand. So distressing to see. But once it was reduced  he gradually gained strength. Good that she is eating and drinking.