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Author Topic: Help desperately needed for 2yo boxer with SRMA, relapsed 2 weeks ago  (Read 383 times)

cowanify

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Desperately needing some advice.

My 2yo Boxer Shiva was diagnosed 12 weeks ago with SRMA and initially quickly improved upon receiving prednisolone which he was on for 6 weeks at 1mg/kg q12h for 6 weeks, followed by 0.5mg/kg q12h for 4 weeks but when we stepped down (too early and too fast I now know, but we were following the advice of the neurologist at the time) he relapsed within days. It also happened a week after cyclosporine was introduced (later discontinued because I saw him going downhill fast on it) and a week after he had anesthetic to biopsy what turned out to be pred-caused Calcinosis on the underside of his tongue.

So we've been back to the original 1mg/1kg dose of prednisolone for 2 weeks and were intending to drop it today, as I'm now following the Mark Lowrie protocol. However last night on manipulation of his neck Shiva growled at me which I interpret as pain and therefore he's still not in remission after the relapse. He also is still walking very slowly and stopping often and has generally low head carriage. But it's hard to tell now, after 12 weeks of pred, what is due to the extreme muscle wastage and weakness and what is due to the SRMA relapsing... but I took the neck pain as still not in remission... so there was not going to be a step down.

I have actually bumped Shiva's pred up to 2mg/kg q12h (ie 4mg/kg per day) for 2 days because that's what is prescribed by the Mark Lowrie protocol upon diagnosis .. but we weren't following that protocol when diagnosed so Shiva never got that 2 day burst of 2mg/kg at the start. So my thinking was to give it to him now, even though it's relapse not first onset, and then revert to 1mg/kg q12h for 12 days before considering starting the taper again? But I've just joined this forum and read that doses above 2.2mg/kg per day have no additional immunosuppressive/anti-inflammatory effect? So I'm wondering why such a high dose would be part of the Lowrie protocol?

I would desperately love some advice. 

Upon relapse does the Michael J Day protocol recommend going back to the original high dose or just the previous dose? Is there anywhere I can read what he has to say on SRMA and treatment? And then, within the 10-28 day window..how do you know when to step down? Do you do blood tests as well as base it on lack of neck pain and how the dog seems? If so, what blood test result would indicate you are good to go ahead and lower the dose?

And, given we relapsed 2 weeks ago, still have neck pain and slow gait (but some of that could be extreme muscle wastage from the 12 weeks of pred?) ... what should we do now... how long do we stay on the current dose before starting a very gradual step down?
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Jo CIMDA

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Re: Help desperately needed for 2yo boxer with SRMA, relapsed 2 weeks ago
« Reply #1 on: January 19, 2019, 02:16:35 PM »

Hi and welcome.

I am sorry  Shiva has relapsed SRMA. 

As you have witnessed, SRMA responds very well and quickly to immunosuppressive treatment but, as you have said, the dose was likely to have been reduced by too much which resulted in Shiva relapsing.  This is not unusual with SRMA. 

Over the last 5+ years, and following 15-20 years of different  'trial and error' immunosuppressive protocols in animals using prednisolone, the most effective protocol that brings the disease under control and into remission, and limits the side effects of the drugs, has been established (although not all clinicians know about it or use it).  The best protocol I have come across is by Michael J Day.  Prof Day is among the top, world leading immunologists and his protocol has worked for so many dogs with autoimmune disease. 

When treating a dog for an AI disease not only does the control of the disease have to be achieved but also a close watch on the side effects produced by the drugs, have to be continually assessed and if necessary the dose has to be reduced even if the disease is not in remission. One cannot treat successfully unless these two points are considered on a daily basis.

It is now known that giving a dose of prednisolone over 1.1mg/kg/12hours will not produce further immunosuppression but it will produce increased adverse clinical signs, some of which can be life threatening.  It is also stated in Plumb's Veterinary Drug Handbook, eighth edition, that a dose of 80mg per day for any dog (regardless of his large size) should not be given.   Lowrie's protocol dates back to 2011. This is only one protocol written by one clinician - there are several. 

 When one of  my dogs developed an AI disease the 'Specialist'  prescribed 2mg/kg/12 hours prednisolone and the adverse effects were numerous.  I queried this high dose with her because I already had experience of treating a dog with an AI disease, and I told her I wanted to lower the dose to 1mg/kg/12 hours and she told me if I did that "I would kill my dog".  Because she was a 'specialist' I listened to her and not my own feelings and experience, and my dog died of a blood clot as a result of the pred dose being too high.  This specialist told me after Bonnie died, that she was working with Cambridge vet school and she and the specialist there have now decided that for a large dog the dose shouldn't exceed 1mg/kg/12 hours.  It was too late for my girl but at least she may have saved other dogs from the same fatal mistake. 

Treating AI diseases in animals is a relatively new area of veterinary medicine but over the last 20 or so years the profession is learning the good and the bad of immunosuppressive therapy.  They also know that recommended doses will vary from species to species.  The dose for a dog is much less than the dose for a cat, for example, and the smaller the animal the higher the dose of prednisolone. Much of this is to do with the faster metabolism of a smaller animal.

This brings us back to Shiva and the best way forward.  Prednisolone is a wonder drug and it has saved many lives  both human and animal but it has to be used correctly or it becomes an enemy.  It is often very hard to tell the difference between the symptoms of the AI disease and the side effects of the preds (and other drugs).  As Shiva has been on prednisolone for many months, he will be having lots of side effects, therefore if further immunosuppression is needed then it is best to introduce another immunosuppressive drug that can work alongside prednisolone and allow the pred to be reduced quicker and more effectively. Using two or more drugs produces increased immunosuppression but reduces the side effects of only using one main drug.  This is common procedure when a dog has relapsed and prolonged, high doses of preds are used. 

Relapses of SRMA are not unusual but if the pred dose is correct and has a good effect and then it is lowered gradually and slowly then remission is very likely.  If a relapse occurs when the dog is off steroids, or down to a low dose, increasing the pred back to 1mg/kg/12hours is the way to deal with a relapse.  You start the whole treatment procedure again.  If a relapse happens whilst the dogs is still on a relatively high dose of preds and has been on preds for several weeks then the adverse clinical signs of the pred may not allow you to raise the dose back to an immunosuppressive dose but if possible it should be increased to the previous level (or to the level that the adverse effects allow) and then another immunosuppressive drug used in combination.  This is a very good website discussing different immunosuppressive drugs.

http://veterinarymedicine.dvm360.com/immunosuppressive-drugs-beyond-glucocorticoids

If Shiva is not on a gastroprotectant then he should be, and  you should ask your vet for some omeprazole.  Also, as Shiva has been on high doses of prednisolone for a long while I would ask ask about adding Aspirin to thin the blood.  This is usual procedure and it can prevent/reduce the risk of blood clots. An antithrombotic dose of Aspirin is 0.5 - 1mg/kg once a day (Plumb's Veterinary Drug Handbook, 8th Edition).  You might also think about adding Denamarin (SAMe and Milk thistle) to support his liver at this time.  When a dog is on immunosuppressive therapy it is prone to pick up infections and sometimes a broad spectrum antibiotic is given to help fight any bacteria that may be present.

You know if you are giving Shiva 2mg/kg/12 hours that his immune system is being significantly suppressed, so it is likely that the clinical signs you are seeing are not due to the SRMA.  I can't tell you how to treat your dog, only a vet can do that, but personally, I wouldn't give 4mg/pred per day especially in a large dog (smaller dogs cope much better with high doses than large dogs). Also, you now know that anything above 1mg/kg/12 hours is not going to have any immunosuppressive benefit and will impact on his tolerance of the steroids.  Can you take Shiva to see a specialist at a vet school or specialist near to where you live?  I don't know where you live but a second opinion might be the best way forward.

If Shiva were mine I would be looking to reduce the preds and to add another drug.  You have tried cyclosporine (not my favourite drug) and Azathioprine will take too long to have any good effect so perhaps your vet might consider a relatively new immunosuppressive drug such as mycophenolate mofetil, which I have heard very good reports about, or Leflunomide, an immunosuppressive drug often used to treat immune mediated polyarthritis. 

I have looked in M J Day's book, Clinical Immunology of the Dog and Cat,  under SRMA for you, he writes: 'Treatment is by long-term, tapered,  therapy immunosuppressive glucocorticoid therapy (oral prednisolone), which leads to clinical improvement and remission from disease.'  His protocol is the best, in my opinion.

When a dog has an AI disease it is a steep learning curve for us, but by the time you have got experience of the dog relapsing and  the signs of drug adverse effects etc., you eventually get a feel for the treatment and when the right time to lower the dose. Blood test will only tell you how much his liver is trying to cope with the effects of the drugs etc, it will not tell you if the diseases is in remission.  The wellness of the dog indicates that.  The only way to tell if SRMA is under control is by examining the synovial fluid from a spinal tap but when a dog is on prednisolone these results will not be accurate so remission is evaluated based on clinical signs -  and you don't want to put Shiva through any unnecessary tests or a general anaesthetic.   

Once an immunosuppressive drug protocol is started, especially with SRMA, you should see good signs of improvement very quickly.  The current dose should be given for at least 10 days but ideally 14-16-18-21 days depending on how the dog is coping with the side effects of the drugs.  If you can get to 18-21 days and the side effects are minimal then that is good and you can lower the dose after 21 days and do the same again for the next few weeks.  If at any time during this time you see unwanted side effects then you have to consider reducing the dose of pred earlier than you had wanted, but this may not be a bad thing.  So it is a bit 'suck it and see'.  Set your target to reduce at about 21 days but be dictated by the clinical signs you are seeing and don't hesitate to reduce the dose if you feel this is right. Monitor closely from 10 days.   It is not clear cut and 'scientific' but we, and our dogs, are all individuals and every protocol has to be tailored to the individual.   It is when the clinician makes hard and fast rules, that they won't adapt to the individual, that big problems arise.  Unfortunately, it is common all over the world.

The long term prognosis for a dog that has SRMA is excellent and there is no reason with correct treatment why Shiva can't reach long  remission  but he may have a few relapses along the way.  Usually SRMA occurs in young dogs and for some reason as they get older this is often not a problem.  It may be more of a juvenile disease.

When a dog has an AI disease it means that they have a genetic predisposition to autoimmunity.  When they reach remission they are 'normal' dogs again but the genetic predisposition still remains, so you need to avoid 'trigger factors' which include vaccination, some drugs, stress, hormones and giving unnecessary regular treatments such as for fleas, worms etc.  Try to keep Shiva as natural as possible.

Jo   



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cowanify

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Re: Help desperately needed for 2yo boxer with SRMA, relapsed 2 weeks ago
« Reply #2 on: January 19, 2019, 07:43:41 PM »

Jo thank you so much for such a caring and detailed response. One immediate question based on this info: can you give human aspirin to a dog? Or what is the name of dog aspirin that I should be asking my neurologist for? And is aspirin ok if his liver values are astronomically high? (ALP 5166, ALT 461)  UPDATE: Jo, I asked our neurologist for this and he said he strongly disagreed. He said that aspirin is not very often used in dogs, that the risk of thrombosis while on pred is very low and the risks of haemorrhage too high. I also ran it past other owners with SRMA dogs and they definitely thought NSAIDs like aspirin were contraindicated in combination with prednisolone?

Also, can you tell me what dosage of prednisolone is considered immunosuppressive and what dosage is considered anti-inflammatory? ie at what point in the protocol does the pred dosage become anti-inflammatory rather than immunosuppressive?

At the moment my plan, given Shiva has been on the 1mg/kg q12h for 15 days now, and with all the adverse effects of the pred, heavily Cushingoid etc, to begin a gradual taper following the Day model ie 0.75mg/kg q12h for at least 10 days starting tomorrow, so we can hopefully ease some of the pred side effects, and then go to 0.5 mg/kg q12h for 10-28 days and so on.

At the moment it's very hard to tell whether the lethargy and slow movement we're seeing is the effects of the pred or lingering SRMA. He hasn't shown neck pain on manipulation today.

All the secondary immunosuppressant drugs seem to come with their own potential serious problems and given Shiva's liver and pred-caused Cushing's and the calcinosis, my feeling is to try to stick with the one drug if at all possible, rather than open him up to another raft of possible unknown side effects and complications, with just a very slower taper, though I want like crazy to have him off it.

One thing I'm not clear on, is, given how hard it is to tell what we're seeing, how do you know where to step down in the 10-28 day window? Are Shiva's side effects serious enough that we step down at 10 days or has he been on the pred so long (3 months) that we need to step down super slow? At what dosage do you think, in your experience, the Cushingoid side effects of the pred should start to ease?
« Last Edit: January 20, 2019, 07:30:28 AM by cowanify »
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Jo CIMDA

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Re: Help desperately needed for 2yo boxer with SRMA, relapsed 2 weeks ago
« Reply #3 on: January 20, 2019, 01:12:35 PM »

WHAT TO EXPECT ONCE IMMUNOSUPPRESSIVE 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 any time 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 corticosteroid can be very serious.  Blood results will reflect this, especially the liver enzymes which may be extremely high. Red blood cells and 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, continuous panting, 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 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.

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 Eighth Edition.

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.
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Jo CIMDA

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Re: Help desperately needed for 2yo boxer with SRMA, relapsed 2 weeks ago
« Reply #4 on: January 20, 2019, 02:32:45 PM »

Hi
To answer your first question, yes you can give human Aspirin to dogs, but the dose has to be correct. An antithrombotic dose, especially in a dog with Cushing's syndrome shouldn't cause bleeding and it should bring the blood levels to within a level that  reduces the risk of blood clots.

You have to either make up your own mind whether the addition of Aspirin at this stage is appropriate to Shiva's treatment or you should seek out another specialist, an internal medicine specialist. Much will depend on how high his platelet count is and also if the red blood cell count (PCV or HCT) is high.  Whether a dog has naturally occurring Cushing's syndrome or drug induced - as Shiva undoubtedly has -  there is a risk of thromboembolic disease.  How high is this risk?  No one can say but a complete blood count will indicate an estimated risk if the platelets and/or the red blood cells are significantly raised or if they are within normal limits.

Not always, but very often when a dog is started on high doses of prednisolone, as a matter of course, the clinician will also prescribe low dose Aspirin and a broad spectrum antibiotic as preventative measures against potential blood clots and infection because the immune system is significantly suppressed.     This preventative treatment will continue until whilst the dose of prednisolone is high.

The dose of oral prednisolone for dogs.  Plumb's Veterinary Drug Handbook, Eighth Edition:

An an anti-inflammatory agent:
0.5 - 1mg/kg per day

As an immunosuppressive:

Dogs: Doses up to 2.2mg/kg/per day.  Doses above 2.2mg/kg/day do not give more immunosuppression but do cause more adverse effects.  If further immunosuppression is required, an additional immunosuppressive drug is needed.  Many internists believe that prednisolone doses should not exceed 80mg per day, regardless of dog's weight.  A sample prednisolone immunosuppressive protocol for dogs follows but doses and dosage schedule must be tailored to the ongoing requirements of the individual patient:

2.2mg/kg/day (not exceeding 80mg total dose per day) for 3 weeks, then 1mg/kg/day for 3 weeks, then 0.5mg/kg/day for three weeks, then 0.5mg/kg every other day.

Client information:
Give oral products with food
Goal is to find the lowest dose possible and use it for the shortest period of time.
Many side effects are possible, especially when it is used for long term.  Most common ones are: greater appetite, thirst, and the need to urinate.
In dogs, stomach or intestinal ulcers, perforation or bleeding can occur.  If your animal stops eating or you notice a high fever, black tarry stools or bloody vomit, contact your veterinarian right away.
Do not stop therapy abruptly (cold turkey) without veterinarians guidance as serious side effects could occur.

The above is a direct quote from Plumb's, which is considered the 'bible' as far as drugs, dosages and extra-label drugs used in veterinary medicine.  Other formulary and drug books are available. The protocol it suggests is different to Prof Day's but as you know there are many different protocols.

Here is an excellent website:
http://veterinarycalendar.dvm360.com/complications-immunosuppressive-therapy-proceedings

The symptoms you are seeing cannot be due to SRMA because Shiva's immune system is so significantly suppressed.  I will post 'what to expect after treatment has started' just in case you haven't seen it on the site.

When a dog has significant side effects from one drug, it is best to introduce another 'combination' drug - even with the different side effects that it brings -  to alleviate the immediate problems.  Once the other immunosuppressive drug is starting to have good effect you can start
to reduce the preds.  As Shiva has been on 1mg/kg/12 hrs for 10 days, and prior to that on much higher doses, then a reduction should alleviate some of his adverse clinical signs within days. The good thing about prednisolone is the levels in the blood reduce after 24-36 hours.  You may still have to introduce another drug but as SRMA  responds so well to steroids (as its name suggests) you may get away with just using prednisolone as a single therapy.  The problem you have at this moment is drug induced Cushing's.  This is so common but unfortunately many vets can't tell the difference between clinical signs of the disease and clinical signs of the side effects of the drugs.  Many Vets in general practice just don't have the experience, and they are not specialists.

 Only your vet is licensed to treat Shiva.  All you can get from here is advice, which can be backed up with reliable references, but ultimately Shiva's treatment has to be decided by you and your vet.

For a dog of Shiva's size, and after being on high doses of prednisolone for 3 months, I would expect his liver enzymes to be very high.  This in itself indicates that, so the most important thing to do now is to reduce those preds so his body can start to return to normal function.  The liver is an amazing organ and as soon as the insult is reduced, it will start to regenerate. The calcinosis is also a direct effect of Shiva's skin barrier breaking down, which is to be expected when a dog has been on such high doses of preds to a long time.  Introducing Natural Vitamin E and essential fatty acids such as evening primrose oil and fish oil will help this. EFA's are known to be 'steroid sparing' but it takes a couple of months to take good effect.  So all that you are seeing is predictable.  It is about getting the balance right, and I think you are about to do that.  It would be so nice for you to have a vet who is reading from the same page though.

The reduction of meds is trial and error.  It is vague because it has to be tailored to the individual.   If things are going well and the dog is coping with the current dose of pred then you may be able to eek out the dose to 21 days but if you see clinical signs that make you think the dose of preds needs to be lowered before this time then that is a priority.  If a dog has been on preds for a long time and he relapses, then an additional drug has to be used because his body will be saturated with the effects of steroids (glucocorticoids). Often it is best to take the very last stages slower, but only if the side effects allow.

Jo
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