Whymper - Border Collie - 8 Months Old - Evan's Syndrome

[jholguin]

Hi everyone, I am so glad I have found this forum. I have been reading it quite a bit since yesterday and it has been of great help. Information is so helpful to help us confront this.

We have an 8 month old Border Collie named Whymper (named after a famous british explorer who was the first to climb up the tallest mountain in our country Ecuador). He is about 16kg in weight.

Friday 27th - Monday 30th:
We took Whymper to the vet last Friday because he was lethargic, his gums were very red and bleeding a little, his nose was bleeding too. Not too much luckily. They diagnosed IMT that same afternoon, got him a platelet transfusion and gave him Coagulants and Prednisone to stabilize him, his bleeding stopped in about 2 days. He has no more bleeding since then. They gave him 1 mg/kg Prednisone, a coagulant, antibiotic and vitamin K.

Tuesday 31st - Wednesady 1st:
They sent Whymper back to our house as he was stable. He spent the night with me. The whole time he seemed very lethargic, he would not eat and seemed very pale. He would groan everytime he sat or layed down, I was worried about this. The next morning we took him to the vet for a control, his gums were very pale and he seemed very weak. They did a blood test (coombs) and the also looked at his RBC. He had high bilirubin. They diagnosed him with IMHA (intravascular) - Evans Syndrome. He has has stayed in the clinic since then. They decided to increase Prednisone to 2 mg/kg and add Aziatophrine 2 mg/kg (plus a GI protector).

Thursday 2nd:
I visited him many times that day, he seems better. He walks with me around in the clinics garden. His urine and stools are fine. He seems more curious, he has been drinking a lot of water and eating food well. He has also been barking and seems more alert. He moves his tail to everyone in the clinic and is good friends with the people there.

One thing I noted is that his nosed has turned from black to brown, is this normal?

Now we are waiting for the progress and see how his next blood test are (I think they will do one either today or tomorrow).

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The vets have been great and we trust them a lot. We haven't found other vets in Quito who have had dogs with Evans. It's the first time in their 50 year practice they get this case. Even if they haven't had this disease before, they have told us they stay up at night reading medical literature and scientific papers on the disease to be up to date, from what I have seen at the forum they seem to be following the right procedure.

I would love to hear your comments on this, and to know how his case looks like compared to other.

Thank you so much!

[Jo CIMDA]

Hi and welcome

Thank you for the lovely picture of Whymper. 

I am so sorry you are having this problem, but you area already seeing an improvement in his clinical signs and now he is on 2mg/kg/day prednisolone  you will hopefully see this turn around and the red blood cells and the platelets will rise.

Your vet seems to be treating Whymper as he should, so that is very good news.  Also, it is a positive sign when they are eating and drinking a lot.  It means that the steroids are working.  It will take a few weeks for the Azathioprine to kick in and by then  the prednisolone will need to be lowered so the Azathioprine will add some extra immunosuppression. 

If you have been looking around the website you will probably have seen the immunosuppressive drug protocol by Prof Michael J Day.   This is the best protocol I have come across and it can be confidently used as a guide to Whymper's treatment.   Prof Day is among the world's top veterinary immunologists. 

Should the platelets drop, then a shot of Vincristine can be considered. Vincristine has the ability to rapidly increase platelet production however, as Whymper is a Border Collie there is a chance that he has the MDR1 gene mutation and if this is the case then Vincristine might not be appropriate.  This can be established by a mouth swab gene test.  I am not sure if this is available in Quito.  More information:  http://vcpl.vetmed.wsu.edu/docs/librariesprovider17/default-document-library/vcplflier.pdf

Don't worry about the change in pigment.  The true colour should return when steroids and the inflammation is reduced.

http://www.pethealthnetwork.com/dog-health/dog-diseases-conditions-a-z/depigmentation-disorders-dogs-changing-skin-color

Skin color changing as a result of outside influences
  According to the Veterinary Internal Medicine textbook, the administration of certain drugs like ketoconazole, procainamide, and vitamin E have been reported to cause generalized changes in coat color in dogs, and injections of other drugs (glucocorticoids, for instance) can cause localized loss of pigment.

Well done to your vets for doing their research.  I hope you have Whymper back home soon.

Jo

The following will give you an idea of what to expect after treatment has started:

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 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.

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 Eight 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.

[jholguin]

Thank you very much Jo!

Whymper is doing a lot better every day! Today he was full of energy and very curious. His RBC count is up to 32 as well (from 16). THey haven't done Platelet counts yet. He is still in the clinic. Luckily here in Ecuador the cost of having him stay in the clinic is very low (about 15-25 usd/night) so we prefer him to be there well taken care off, resting, and he likes the place. We might bring him back home on Monday.

I wanted to ask you about vincristine, and what we could expect if he ever needs to get it? How strong are its side effects? Some of my family members wouldn't want him to take more meds if pred/azo fail because they wouldn't want him to suffer too much, but having more information would be good for all.

[Jo CIMDA]

Hi

Whymper is responding well to the current treatment so as long as the reducing protocol is correct then  there is a good chance of it being successful and achieving long term remission.   Yes, relapses can occur but if this happens then you return to immunosuppressive doses of preds and the drug regimen starts all over again.  As the bone marrow responded before then it is likely to respond again. 

Using other immunosuppressive drugs is common, so I wouldn't be put off if this is necessary.
This is a very good link to immunosuppressive drugs used to treat immune mediated disease.

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

It is going well.

Jo