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Author Topic: Treatment regimes, what to expect, Iatrogenic Cushings and relapses  (Read 30726 times)

Penel CIMDA moderator

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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  Your dog could go into an adrenal crisis if the medication is withdrawn too quickly.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. Zantac does not inhibit the absorption of the drugs. Another gastroprotectant used is omeprazol. 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, who 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 Cushings 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 CUSHINGS 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 prolonged 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 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.

Reduction Protocol for prednisolone:
Protocol 1
Canine Medicine and Therapeutics by Neil Gorman
1-2mg/kg/12hrs for 10-28 days (starting at the lowest immunosuppressive dose)
Assuming blood results are good, and the dog is coping with the side effects of the drugs, the dose can be reduced by up to 50%. 
This dose is given for another 10-21 days when the dose is reduced again by up to 50%.
This dose is given for another 10-21 days when the dose is reduced again by up to 50%. 
For the next reduction the dose remains the same but given every other day (EOD). The EOD dosing is reduced by up to 50% every month or so until the dose is so low a decision can be made to keep the dog on this low maintenance dose or withdraw altogether. Every reduction is made after consideration to clinical signs and blood results.

Protocol 2
Clinical Immunology of the Dog & Cat , 2nd Edition,  by Michael J Day
This example is base 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   

Either of the protocols should work but it always depends on how the dog is improving and coping with 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 the very much depends on the individual dog, the severity of the disease 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 long period without drugs or on EOD maintenance drugs, then a relapse occurs or he develops another autoimmune disease, he has encountered a ‘trigger factor’ which has induced this change.
« Last Edit: May 25, 2012, 09:05:31 PM by Jo CIMDA »
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Penel
(SLE, Surrey - UK)
Forum Owner
CIMDA