What to do...

[Michelle]

Hi Jo and others
Our Miniature Schnauser Nala is struggling with thus terrible disease. She's been diagnosed in May 2017 and us really trying. She's 2 years old. The last 2 weeks she's been down and lethargic. No energy. We took her for a walk and her legs keep giving in. She can't jump on the bed anymore. She's just lying down the whole day. She now has a nose infection. We are starting to think that she is suffering.
She is on
Atopica 50mg 1 tablet daily
Azathioprine 50mg 0.5 tablet daily
Prednisone 5mg 2 tablets twice daily
Omez 10mg 1 capsule twice daily
Aspirin 300mg 0.25 tablet mixed with 5ml water and only 0.7ml administered once daily
Her current PCV is 40. Her temperature 39.4

What do you suggest we do? Her prednisone was lowered from 2.5 tablets to 2 twice daily 2 days ago after being on 2.5 tablets twice daily for 3 weeks.

Please help.
Michelle

[Catherine]

I know it is difficult to see her struggling but it is still early days yet after her becoming very ill so it will take some time. The good news is that her PCV is 40 so hopefully it will continue to rise a little or stabilise around that figure.

The Preds. might be causing her leg weakness but the Atopica could be the reason. I have not had experience with it only Azathioprine. But I have heard some dogs feel sick with it and also there seems to be a lot of leg weakness as well. Perhaps you could ask your vet if she needs to be taking the Atopica still especially as she is still having the Azathioprine?

Have you had a biochemistry blood test for her to check her kidneys and liver values etc. recently?

It might be best to just take her for gentle walks around the garden until her legs improve. When is her next blood test?

[Jo CIMDA]

Hi Michelle

Why is Nala still on 20mg of prednisolone a day?  The dose should have been significantly weaned down by now to a very low every other day dose.  The symptoms you are seeing is as a result of the drugs and mostly the preds. Her PCV is 40, so there is no need for her to be on this very heavy drug regimen.  The drugs have done the job and there is no doubt that  problems you are seeing now is the effect of the drugs.  She will be struggling.

You should start by lowering the preds.  Usually the best way to lower the preds is gradually but as Nala has been on high doses since May then you should consider lowering them significantly (by 50%) to reduce the side effects that you are seeing.  Within a few days you should notice a difference.  I am not surprised she is not coping and it is tough on you seeing her like this.   

The nose problem is also as a result of her being on high doses of immunosuppressive drugs and the preds will cause her skin to become thin and lesions are common.   To see an improvement in Nala you have to remove the cause and you should start with significant prednisolone reduction.   You cannot stop the preds suddenly, because her adrenal glands have to have the chance to kick back in and resume normal function,  but it is essential to reduce them.

I hope your vet complies and if he or she doesn't then please get a referral to someone who knows more about immunosuppressive treatment and the side effects of prednisolone. Nala can return to her normal self but only if the preds are lowered and she is gradually weaned off the drugs or down to a low every other day dose.

Jo

Below is an extract from my notes:

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. 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.

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.

"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.